Pharmacist perceptions of a "good death" and differences in perception between patients with cancer, oncologists, and oncology nurses: a questionnaire survey.

BACKGROUND: For pharmacists expected to encounter the deaths of many of their patients in the near future, it is important to understand the perception of a "good death" for patients with cancer who are likely to be aware of the circumstances of their poor prognosis. In this study, we clarified pharmacists' perceptions of a "good death" and considered the differences in perception among patients with cancer, oncologists, and oncology nurses. METHODS: From April to June 2022, an anonymous questionnaire survey was conducted on pharmacists working in hospitals and pharmacies and on members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. The questionnaire consisted of 57 questions, called attributes, developed by Miyashita et al. to investigate the perception of "good death" in Japanese cancer medicine. The importance of those attributes was investigated using a 7-point Likert scale. RESULTS: Three thousand four hundred thirty-two pharmacists were made aware of this survey, and 207 participated in the survey. The responses of pharmacists to the 57 questions were very similar to those of the oncologists. Among them, "Fighting against disease until one's last moment" and "Not making trouble for others" had very low importance, which was the most significantly different from the responses of patients with cancer. "Fighting against disease until one's last moment" tended to be significantly underestimated by pharmacists engaged in patient guidance and interview compared to that by pharmacists not engaged in the duty (p = 0.02). Also, when we compared pharmacists with or without qualifications related to cancer and palliative care, there was no significant difference in the importance of "Fighting against disease until one's last moment." However, the importance of "Not making trouble for others" for qualified pharmacists was significantly underestimated (p = 0.04). CONCLUSION: Since pharmacists understand the limits of chemotherapy, they may want to be close to the patient but may not strongly agree with the "Fighting against cancer" component that patients with cancer prefer. It may be necessary to reconsider better ways of approaching the wishes and satisfaction of patients with cancer under the care of medical professionals in the field of oncology.

Role of afadin in vascular endothelial growth factor- and sphingosine 1-phosphate-induced angiogenesis.

RATIONALE: Angiogenesis contributes to physiological and pathological conditions, including atherosclerosis. The Rap1 small G protein regulates vascular integrity and angiogenesis. However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin cytoskeleton and binds activated Rap1, plays a role in angiogenesis. OBJECTIVE: We investigated the role of endothelial afadin in angiogenesis and attempted to clarify the underlying molecular mechanism. METHODS AND RESULTS: Treatment of human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF) and sphingosine 1-phosphate (S1P) induced the activation of Rap1. Activated Rap1 regulated intracellular localization of afadin. Knockdown of Rap1 or afadin by small interfering RNA inhibited the VEGF- and S1P-induced capillary-like network formation, migration, and proliferation, and increased the serum deprivation-induced apoptosis of HUVECs. Knockdown of Rap1 or afadin decreased the accumulation of adherens and tight junction proteins to the cell-cell contact sites. Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K), recruitment of the afadin-PI3K complex to the leading edge, and the activation of Akt, indicating the involvement of Rap1 and afadin in the PI3K-Akt signaling pathway. Binding of afadin to Rap1 regulated the activity of Rap1 in a positive-feedback manner. In vivo, conditional deletion of afadin in mouse vascular endothelium using a Cre-loxP system impaired the VEGF- and S1P-induced angiogenesis. CONCLUSIONS: These results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis.

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation.

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor.

Afadin is an actin-filament-binding protein that binds to nectin, an immunoglobulin-like cell-cell adhesion molecule, and plays an important role in the formation of adherens junctions. Here, we show that afadin, which did not bind to nectin and was localized at the leading edge of moving cells, has another role: enhancement of the directional, but not random, cell movement. When NIH3T3 cells were stimulated with platelet-derived growth factor (PDGF), afadin colocalized with PDGF receptor, alphavbeta3 integrin and nectin-like molecule-5 at the leading edge and facilitated the formation of leading-edge structures and directional cell movement in the direction of PDGF stimulation. However, these phenotypes were markedly perturbed by knockdown of afadin, and were dependent on the binding of afadin to active Rap1. Binding of Rap1 to afadin was necessary for the recruitment of afadin and the tyrosine phosphatase SHP-2 to the leading edge. SHP-2 was previously reported to tightly regulate the activation of PDGF receptor and its downstream signaling pathway for the formation of the leading edge. These results indicate that afadin has a novel role in PDGF-induced directional cell movement, presumably in cooperation with active Rap1 and SHP-2.

Involvement of the nectin-afadin complex in PDGF-induced cell survival.

The nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJs) and tight junctions (TJs). Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, whereas afadin is an intracellular nectin-binding protein that connects nectins to the cadherin-catenin system at AJs and to the claudin-zona-occludens (ZO) protein system at TJs. Afadin(-/-) mice show embryonic lethality, resulting from impaired migration and improper differentiation of cells due to disorganization of cell-cell junctions during gastrulation. However, it remains to be elucidated whether disruption of afadin affects apoptosis. In the present study, we first found that embryoid bodies derived from afadin-knockout embryonic stem (ES) cells contained many more apoptotic cells than those derived from wild-type ES cells. We also revealed that apoptosis induced by serum starvation or Fas-ligand stimulation was increased in cultured NIH3T3 cells when afadin or nectin-3 was knocked down. The nectin-afadin complex was involved in the platelet-derived growth factor (PDGF)-induced activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling for cell survival. This complex was associated with PDGF receptor on the plasma membrane at cell-cell adhesion sites. Thus, the nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway.

Helicobacter pylori augments growth of gastric cancers via the lipopolysaccharide-toll-like receptor 4 pathway whereas its lipopolysaccharide attenuates antitumor activities of human mononuclear cells.

PURPOSE: Helicobacter pylori is reportedly involved in the development of gastric cancer. We investigated the mechanisms by which H. pylori affects gastric cancer growth and antitumor immunities in the host, focusing on H. pylori-derived lipopolysaccharide (LPS). EXPERIMENTAL DESIGN: H. pylori and four gastric cancer cell lines (MKN28, MKN45, NUGC3, and KATOIII) were used. We examined the effect of H. pylori or its LPS stimulation on cancer growth and the involvement of the H. pylori LPS-toll-like receptor 4 (TLR4) pathway. We also examined the cytotoxicities of H. pylori/LPS-stimulated human mononuclear cells (MNC) against gastric cancer cells and the effect of H. pylori LPS stimulation on cytokine production by MNC. RESULTS: H. pylori, as well as its LPS, augmented the growth of gastric cancers, all of which expressed TLR4. Neutralization of TLR4 almost completely abrogated the H. pylori-induced proliferative activity of cancer cells. Escherichia coli LPS also augmented cancer growth via the LPS-TLR4 pathway. However, only H. pylori-derived LPS attenuated the cytotoxicity of MNC against gastric cancer cells. Stimulation with H. pylori/LPS also down-regulated perforin production in cancer cell-cocultured CD56+ natural killer cells. H. pylori LPS induced neither interleukin-12 nor IFN-gamma production by MNC, although E. coli LPS did induce production of both significantly. Nevertheless, interleukin-12 stimulation restored the IFN-gamma-producing capacity of H. pylori LPS-stimulated MNC. CONCLUSION: H. pylori augmented the growth of gastric cancers via the LPS-TLR4 pathway, whereas it attenuated the antitumor activity and IFN-gamma-mediated cellular immunity of MNC. H. pylori infection might thereby promote proliferation and progression of gastric cancers.

Gastric cancer cells exploit CD4+ cell-derived CCL5 for their growth and prevention of CD8+ cell-involved tumor elimination.

The level of serum CCL5, a C-C chemokine, is reportedly correlated with tumor progression in several cancers. We herein investigated the mechanisms by which CCL5 might contribute to tumor progression in gastric cancer. Serum CCL5 levels significantly correlated with tumor progression and prognosis in patients with gastric cancer. Immunohistochemistry showed that tumor-infiltrating lymphocytes expressed CCL5, while the tumor cells expressed the CCL5 receptors. Fluorescent double staining showed that tumor-infiltrating CD4+ cells rather than CD8+ cells preferentially expressed CCL5. Using gastric cancer cell lines (MKN45, KATO III), we examined CCL5 production by coculturing whole peripheral blood mononuclear cells (PBMCs), CD4+ cells, or CD8+ cells, with tumor cells. CD4+ cells cocultured with tumor cells remarkably enhanced CCL5 production in a direct cell-cell contact manner over other cocultured PBMCs, including CD8+ cells. Gastric cancer cell lines expressed CCL5 receptors and augmented their proliferation in response to CCL5 stimulation. Furthermore, we examined the effect of CCL5-treated cancer cells on the cocultured PBMCs, focusing on the CD4+/CD8+ proportion and apoptosis. Coculture of CCL5-treated gastric cancer cells with PBMCs resulted in a significant decrease in the proportion of CD8+ cells but not CD4+ cells, suggesting Fas-FasL-mediated apoptosis in CD8+ cells. In immunodeficient mice coinjected with KATO III and PBMCs, neutralization of CCL5 significantly suppressed tumor progression, resulting in a favorable outcome. In conclusion, gastric cancer cells might thus induce CD4+ T cells to secrete CCL5 and exploit it for their progression, as well as to aid in the prevention of CD8+ T cell-involved tumor elimination.

A tissue-engineered stomach shows presence of proton pump and G-cells in a rat model, resulting in improved anemia following total gastrectomy.

Despite advances in surgical reconstruction, total gastrectomy still is accompanied by various complications, especially chronic ones, such as pernicious anemia, resulting in refractory malnutrition. As an alternative approach, we have proposed a tissue-engineered stomach as a replacement of the native stomach. This study aimed to assess the secretory functions of a tissue-engineered stomach in a rat model and the nutritional status of the recipients over an extended time period. Stomach epithelial organoid units were isolated from neonatal rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of adult recipient rats. After 3 weeks, cyst-like structures had formed, henceforth referred to as tissue-engineered stomachs. The recipient stomachs were resected and replaced by their tissue-engineered counterparts. At 24 weeks after implantation, the secretory function of the tissue-engineered stomach was evaluated using immunohistochemical staining. The hemoglobin levels and nutritional status of the recipients were compared with a control group that had undergone a simple Roux-en-Y reconstruction following total gastrectomy. Recipient rats tolerated the tissue-engineered stomachs well. X-ray examination using barium as contrast showed no bowel stenosis. Staining for proton pump alpha-subunit and gastrin demonstrated the existence of parietal cells and G-cells in the neogastric mucosa, respectively, suggesting secretory functions. The treatment group showed significantly higher hemoglobin levels than the control group, although no differences in the body weight change, total protein, or cholesterol levels were observed between the two groups. A tissue-engineered stomach has the potential to function as a food reservoir following total gastrectomy. It is conjectured that replacement with a tissue-engineered stomach might restore the proton pump parietal cells and G-cells, and thereby improve anemia after a total gastrectomy in a rat model.

Serum granulysin level as a novel prognostic marker in patients with gastric carcinoma.

BACKGROUND: Granulysin is a cytolytic molecule present in human cytotoxic T cells and natural killer cell granules, and plays a key role in the cell-mediated immunity against tumor and infection. However, few studies have estimated serum granulysin concentrations in patients with solid or hematological malignancies. METHODS: Peripheral blood samples were taken from patients with gastric carcinoma preoperatively and from healthy volunteers. Serum and tumor tissue granulysin concentrations were measured using a granulysin-specific ELISA kit in order to assess its prognostic value. RESULTS: Both serum and tumor tissue granulysin concentrations were higher in patients with stage II or III gastric cancer and lower in patients with stage IV disease as compared to healthy controls. The low preoperative granulysin levels were associated with more frequent hepatic and peritoneal metastases, and with a poor outcome of the curative gastrectomy. CONCLUSIONS: Preoperative serum granulysin levels reflect the status of cell-mediated immunity in patients with gastric carcinoma. It has significance as a prognostic determinant following a curative resection.

Differential toll-like receptor expression after ex vivo lipopolysaccharide exposure in patients with sepsis and following surgical stress.

INTRODUCTION: Monocytes from septic patients have a reduced capacity to respond to lipopolysaccharide (LPS). We examined whether the same response occurred after surgical injury, and whether this reduced activity was associated with differential monocyte toll-like receptor (TLR) expression. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from septic patients, patients undergoing surgery, and healthy volunteers. Cells were stimulated ex vivo with LPS (1 microg/ml) and stained for CD14, CD16, TLR-2, TLR-4, and HLA-DR surface expression. RESULTS: TLR-2 and -4 expressions were significantly increased in monocytes from both septic and surgical patients. While ex vivo LPS-stimulation significantly increased TNFalpha and IL-1beta production in PBMCs from surgical patients, LPS-stimulation decreased IL-1beta production from septic patients as compared to surgical and control patients. Ex vivo LPS-stimulation induced TLR-4 upregulation in monocytes from both surgical and control patients, but not from septic patients. HLA-DR expression in CD14+CD16+ monocytes was reduced only in septic patients. CONCLUSIONS: PBMCs from septic patients, but not following surgical injury, have a reduced capacity to respond to a secondary inflammatory signal, but this defect is not associated with reduced TLR-4 or CD14 expression.

Exploitation of interleukin-18 by gastric cancers for their growth and evasion of host immunity.

Interleukin-18 (IL-18) is a pleiotropic cytokine that enhances Th1 or Th2 immune response. We show a novel mechanism of gastric cancer cells that allows their immune escape utilizing IL-18. All 4 gastric cancer cell lines, but not colon lines, constitutively expressed IL-18 receptors and IL-18 dose-dependently enhanced their in vitro proliferation accompanied by nuclear factor kappaB activation. When IL-18-pretreated gastric cancer cells were cultured with cytokine-activated peripheral blood killer lymphocytes, the antitumor machineries, perforin or interferon-gamma production of killer lymphocytes decreased, resulting in a decreased susceptibility of cancer cells to killer lymphocytes. Furthermore, gastric cancer cells cultured with IL-18 showed an increased expression of a granzyme B inhibitor, protease inhibitor 9. IL-18 injections into severe combined immuno-deficient mice intraperitoneally inoculated with gastric cancer cells consistently decreased the mouse survival time. Our results indicate that gastric cancers exploit IL-18 to grow/invade and evade immunosurveillance in the hosts.

Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis.

Highly activated neutrophils play a critical role in mediating organ injury in sepsis by releasing neutrophil elastase (NE). Toll-like receptors (TLRs) play an important role in the host defense against invading microbes, and their signaling pathway is critical to the activation of the proinflammatory response. However, the relationship between TLR expression and the host defense mechanism during sepsis has not been fully elucidated. In this paper, we investigated the relationships among chemokine (MIP-2), TLR-4, and NE expression in human sepsis and murine peritonitis (CLP). TLR-4 expression on monocytes/macrophages was examined in patients with sepsis and in murine peritonitis and was markedly increased in both populations. LPS-induced MIP-2 production by bronchoalveolar cells and liver mononuclear cells in mice with peritonitis was also significantly increased compared with sham-operated mice. Pretreatment of the macrophage cell line, RAW 264.7 cells, with a NE inhibitor before their exposure to LPS resulted in a significant dose-dependent decrease in MIP-2 production, which was comparable to that seen following pretreatment with TLR-4 antibody. Furthermore, NE and LPS both up-regulated TLR-4 expression on human peripheral blood monocytes. Thus, chemokine-induced recruitment of neutrophils in sepsis may result in further increased chemokine production and increased expression of TLR-4. Neutrophil-derived NE may be associated with increased expression of monocyte/macrophage TLR-4, thereby serving as a positive feedback loop for the inflammatory response among the different cell populations.

Evaluation of the Japanese Gastric Cancer Association's Gastric cancer treatment guidelines for popular use.

BACKGROUND: The Japanese Gastric Cancer Association's (JGCA's) Gastric cancer treatment guidelines for doctors' reference and the guidelines (GLs) for popular use were both published in 2001. The purpose of this study was to know whether or not it is useful for patients to read the GLs for popular use. METHODS: We lent the GLs for popular use to patients with gastric cancer for several days and had them read the GLs before they were informed about their condition and the recommended treatment. Then they received questionnaires concerning the GLs. RESULTS: Most of the patients, even the elderly, had read and understood the GLs. Nearly 70% of the patients answered that it was very useful for them to read the GLs. On the other hand, 34% of the patients suggested negative aspects, such that reading the GLs increased their anxiety about the disease or treatment. Only 9% of the patients expected treatment that followed the GLs, whereas 54% of the patients expected treatment based on the doctor's own experience without adherence to the GLs. If the doctor were to suggest treatment that did not follow the GLs, 87% of the patients answered that they would follow the doctor's suggestion, and it was only 8% who answered that they would seek a second opinion. These results did not differ when patients were requested to fill out questionnaires anonymously. CONCLUSION: Although the GLs for popular use are useful to provide patients with information concerning the disease and the treatment modalities, they may not have a great impact on patients' decisions about their treatment.

The increase of CD57+ T cells in the peripheral blood and their impaired immune functions in patients with advanced gastric cancer.

In addition to natural killer (NK) cells, T cells expressing natural killer cell markers, CD56 or CD57 (NK type T cells), have been considered to play an important role in antitumor immunity. We examined the proportion of NK cell and NK type T cell subsets in the peripheral blood from patients with gastric cancer. The IFN-gamma production capacity and population of cytoplasmic perforin positive cells in peripheral blood mononuclear cells (PBMC) were evaluated. Peripheral blood samples were obtained from 56 patients with gastric cancer and 21 healthy volunteers. The proportion of CD56- CD57+ T cells (CD57+ T cells) was significantly higher in advanced gastric cancer patients than those in healthy volunteers and patients with early stage gastric cancer, whereas no correlation was observed between the proportion of CD56+ T cells or NK cells and tumor progression. Furthermore, a significant decrease of CD8+ CD57+ T cells was found in patients with advanced gastric cancer. The proportion of CD57+ T cells did not correlate with interferon-gamma (IFN-gamma) production from PBMC in gastric cancer patients, although a significant correlation was found between them in healthy volunteers. The proportion of perforin positive CD57+ T cells, especially CD8+ CD57+ T cells, in patients with gastric cancer was markedly lower than that in healthy volunteers. Collectively, although the proportion of CD57+ T cells in PBMC was found to increase with tumor progression, their function in antitumor immunity is impaired in patients with gastric cancer.

Cutting edge: the NK cell receptor 2B4 augments antigen-specific T cell cytotoxicity through CD48 ligation on neighboring T cells.

2B4 is expressed on all NK and a subset of memory/effector CD8(+) T cells. 2B4 binds to CD48 and activates NK cytotoxicity, but its function on CD8(+) T cells is not clear. Furthermore, two isoforms of 2B4 (2B4S and 2B4L) exist in mice but the role of individual isoforms is not known. To address these questions, we generated primary T cell cultures from L(d)-specific 2C/Rag2(-/-) TCR transgenic mice and transduced them with 2B4S or 2B4L. 2B4S- or 2B4L-transduced T cells showed greater cytotoxicity over control cells against CD48(+) and CD48(-) targets, suggesting that ligation of 2B4 by CD48 on target cells was not necessary for 2B4 function. Rather, 2B4/CD48 interaction on adjacent T cells appeared to be critical for cytotoxicity. Therefore, 2B4 functions as a costimulator of CD8(+) T cells in MHC-restricted cytotoxicity. We conclude that 2B4/CD48 interactions among T cells themselves can augment CTL lysis of their specific targets.

Functional and Vbeta repertoire characterization of human CD8+ T-cell subsets with natural killer cell markers, CD56+ CD57- T cells, CD56+ CD57+ T cells and CD56- CD57+ T cells.

We investigated the individual CD8+ populations with natural killer (NK) cell markers (NK-type T cell); CD56 single positive (CD56)-T cells, CD56/CD57 double positive (DP)-T cells and CD57 single positive (CD57)-T cells in the peripheral blood. All NK-type T-cell populations expressed CD122 and intermediate levels of T-cell receptor (TCR; regular CD8+ T cells are CD122- and express high levels of TCR). The number of both DP-T cells and CD57-T cells, but not CD56-T cells, gradually increased with age. All NK-type T-cell populations produced larger amounts of interferon-gamma than did regular CD8+ T cells after stimulation with interleukin (IL)-2, IL-12 and IL-15. However, CD56-T cells and CD57-T cells but not DP-T cells showed a potent antitumour cytotoxity to NK-sensitive K562 cells, whereas only CD56-T cells showed a potent cytotoxity to NK-resistant Raji cells. Furthermore, although NK-type T cells produced large amounts of soluble Fas-ligands, their cytotoxic activities appeared to be mediated by the perforin/granzyme pathway. The oligoclonal or pauciclonal expansions of certain VbetaT cells were found in each NK-type T-cell population. The non-variant CDR3 region(s) for the TCRbeta chain(s) showed CD57-T cells and CD56-T cells to be derived from distinct origins, while the DP-T cell population consisted of a mixture of the clones seen in both CD56-T cells and CD57-T cells. Our results suggest that CD57-T cells and CD56-T cells are functionally and ontogenically different populations while DP-T cells appear to originate from both CD56-T cells and CD57-T cells.

The influence of interleukin-10 and interleukin-18 on interferon-gamma production by peritoneal exudate cells in patients with gastric carcinoma.

Although the peritoneal cavity (PC) is the most common site of metastasis in gastric carcinoma, its immune status in patients with advanced cancer remains largely unknown. We investigated the relationship between clinical parameters and cytokine levels in the PC and also evaluated IFN-y production by peritoneal exudate cells (PEC), obtained during surgery from patients with stage III-IV gastric carcinoma. Although the IFN-gamma and IL-12 levels in the PC did not differ between stage III and stage IV cancer patients, the latter had higher levels of IL-10 and IL-18. Those patients with higher IFN-gamma levels experienced a significantly better survival-rate than those with lower IFN-gamma levels, whereas IL-18 (but not IL-10) levels were inversely-correlated with survivaL IFN-gamma levels increased in parallel with IL-18 levels in patients who survived more than two years, but this correlation did not apply to patients who died of disease within two years. In addition, anti-CD3-Ab or cytokine- stimulated PEC from patients with low IL-10 levels in their PC produced a significantly greater amount of IFN-gamma than PEC from patients with high PC IL-10 levels. In conclusion, a high level of IFN-y in the PC is an indicator of favorable outcome. Both IL-10 and IL-18 levels in the PC increased with tumor progression. Although the number of PEC capable of producing IFN-gamma increases with tumor progression, their ability to secrete IFN-gamma in response to IL-18 may be influenced by local IL-10 levels in the PC.

Prognostic significance of the cytologic features of free cancer cells in the peritoneal cavity of patients with gastric cancer.

The aim of this study was to determine whether the cytologic features of cancer cells in the peritoneal lavage fluid from patients undergoing surgery for gastric cancer affect prognosis. A total of 141 patients with stage III-IV gastric cancer were enrolled in this study. Among 111 patients without peritoneal metastasis (P0), 43 were noted to have positive peritoneal cytology (P0/CY1). These patients were subclassified into two groups according to the cluster formation of cancer cells in the cytology specimen, namely, 17 with cluster formation and 26 without cluster formation. The clinicopathologic parameters and survival rates were compared between these two groups. Among the P0/CY1 patients, no significant difference in clinicopathologic features existed between patients with or without the cluster formation of cancer cells. However, the survival rate of patients without cluster formation was significantly higher than that of those with cluster formation. Furthermore, the survival curves of patients without cluster formation was similar to that of the P0/ CY0 patients with stage IV cancer. Subclassification according to the presence or absence of the cluster formation of cancer cells may be useful for predicting the outcome of patients with positive cytology after surgery for advanced gastric cancer.

Sentinel node concept in gastric carcinoma.

To assess the applicability of the sentinel node concept to gastric carcinoma. The location of metastatic lymph nodes was analyzed retrospectively in 119 patients with gastric carcinoma in whom metastasis was limited to one or two nodes. Intraoperative lymphatic mapping was attempted in 62 patients using indocyanine green injected endoscopically into the gastric submucosa adjacent to the tumor. Metastatic lymph nodes were distributed beyond the perigastric area in 4% of patients with a single node involved. The positive node was located along the greater curvature in 21% of the patients with a tumor on the lesser curvature. Two patients had a metastatic node totally occupied by cancer tissue. In 16% of patients with two nodes involved, a positive node was located on both the lesser and greater curvatures. Lymphatic mapping was successful in all subjects. A larger number and wider distribution of green-stained nodes were observed in patients injected with 8 ml of indocyanine green solution than in those injected with 4 ml. No metastasis was observed in any nodes in 47 (96%) of the 49 patients who had no metastasis in green nodes. In one patient showing metastasis in non-green nodes without metastasis in green nodes, the positive nodes were totally occupied by cancer tissue. Our results showed the complexity of lymphatic streams within and from the stomach. Lymphatic mapping using indocyanine green can be a tool for identifying sentinel nodes in gastric carcinoma although lymph nodes occupied by cancer tissue may not be detected by this technique.