Koshiro Hioki

The superiority of ratio-based lymph node staging in gastric carcinoma

AbstractBackground: The need for a precise lymph node staging without stage migration is of paramount importance when comparing and evaluating international treatment results. Methods: We reviewed 1019 patients who underwent R0 resection at Kansai Medical University between 1980 and 1997. The patients were classified according to the 1997 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) pN classification or the N staging depending on the ratio between the number of excised and the number of involved lymph nodes (pN1, ≤25%; pN2, ≤50%; pN3, >50%). Results: Among the 1997 UICC/AJCC pN subgroups, prognosis worsened with an increase in lymph node ratio. In contrast, the ratio-based classification showed more homogenous survival according to the number of involved lymph nodes. Multiple stepwise regression analysis showed that the ratio-based classification was the most significant prognostic factor, whereas the 1997 UICC/AJCC classification was not found to be an independent predictor of survival. In addition, the ratio-based classification showed a superiority to the 1997 UICC/AJCC classification with respect to stage migration. Conclusions: Ratio-based lymph node staging is simple and gives more precise information for prognosis with fewer problems related to stage migration than the 1997 UICC/AJCC staging system.

Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator

Abstract Resveratrol is a naturally occurring product found in grapes and wine. The effect of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined. Resveratrol at low concentrations caused cell proliferation in ER-positive lines (KPL-1, ≤22 μM; MCF-7, ≤4 μM) whereas at high concentrations (≥44 μM) it caused suppression of cell growth in all three cell lines examined. Growth suppression was due to apoptosis as seen by the appearance of a sub-G1 fraction. The apoptosis cascade up-regulated Bax and Bak protein, down-regulated Bcl-xL protein, and activated caspase-3. Resveratrol (52–74 μM) antagonized the effect of linoleic acid, a potent breast cancer cell stimulator, and suppressed the growth of both ER-positive and -negative cell lines. Thus, resveratrol could be a promising anticancer agent for both hormone-dependent and hormone-independent breast cancers, and may mitigate the growth stimulatory effect of linoleic acid in the Western-style diet.

Jejunal pouch reconstruction after total gastrectomy for cancer. A randomized controlled trial.

ObjectiveThe authors determined the optimum reconstruction procedure after total gastrectomy in terms of the quality of life of the patients. Summary Background DataGastric replacement with various enteric reservoirs has been used to improve the postprandial symptoms and nutrition of patients after total gastrectomy. However, the effect of each is uncertain because no prospective randomized studies have been conducted. MethodsA randomized controlled trial was conducted to compare the usefulness of the three reconstruction procedures of simple Roux-en-Y (RY; N = 10), pouch and Roux-en-Y (PR; N = 10), and pouch and interposition (PI; N = 10). In each subject, the postprandial symptoms, food intake in a single meal, body weight, serum nutritional parameters, and emptying time of the gastric substitute were evaluated. ResultsThe PR group showed significantly greater food intake in a single meal than the RY and PI groups, and greater weight recovery than the PI group. A gastric emptying test also revealed satisfactory retention capacity and emptying time of the gastric substitute in the PR group. ConclusionsPouch and Roux-en-Y reconstruction is the most useful of the three procedures for improving the postoperative quality of life. In patients with pouch and interposition reconstruction, the clinical assessment was quite poor, even though it is a physiologic route.

Physiologic and anatomic assessment of patients with rectocele.

Clinical, physiologic, and anatomic assessments were carried out in 22 female patients with symptomatic rectocele (Group A), 15 patients with asymptomatic rectocele (Group B), and 14 subjects having no rectocele (Group C). Resting anal pressure, rectal pressure, rectal compliance, anorectal inhibitory reflex, and rectal sensation did not differ among the groups. Proctography revealed that the lengths of the rectocele during attempted defecation in groups A (1.6 [1.0–3.5] cm) (median and range) and B (1.6 [1.0–3.0] cm) were significantly greater than that in Group C (0.4 [0.1–0.9] cm) (P<0.001 in both groups). Median pelvic floor descent at rest in Groups A (4.3 [1.6–7.5] cm) (median and range) and B (4.3 [1.3–6.9] cm) were significantly greater than that in Group C (2.5 [1.2–5.0] cm) (P<0.001 andP<0.02, respectively). These results indicate that rectocele is not associated with any physiologic change apart from a significant increase of pelvic floor descent.

Structural and functional alterations in the gut of parenterally or enterally fed rats

Various regimens of total parenteral nutrition (TPN) and enteral feeding were compared to determine their effects on the structural and functional changes of rat small intestine. Male Wistar rats, allocated randomly into five groups on the basis of delivery route and composition of nutrients, were fed as follows: standard rat chow ad libitum (CE-2 group), low-residue diet (LRD group), LRD supplemented with 1% (w/v) fiber (LRD + fiber group), elemental diet (ED group), and TPN (TPN group). At 2 weeks of feeding, villi in the terminal ileum decreased in height in the following order: CE-2 group greater than LRD + fiber group greater than LRD group greater than ED group greater than TPN group. Mucosal diamine oxidase activity remained unchanged in the CE-2 group and LRD + fiber group throughout the experimental period. However, mucosal diamine oxidase values were significantly lower in the remaining three groups, similar to the structural changes, and those values in the ED group were significantly decreased at 2, 3, and 4 weeks. There was a positive correlation between plasma diamine oxidase level and mucosal diamine oxidase content, with a coefficient correlation of y = 0.20x + 0.03, r = 0.55 (P less than 0.01). These results could be interpreted to indicate that addition of dietary fiber to LRD has a favorable effect on the maintenance of intestinal architecture and function during enteral feeding, and plasma diamine oxidase activity can be used as an index of functional and/or structural changes occurring in the small intestine during enteral or parenteral feedings.

Changing Site Distribution of Colorectal Cancer in Japan

AbstractPURPOSE: In North America and other high-risk areas, there has been a proximal shift in the subsite distribution of colorectal cancer. We wanted to determine whether any similar change has occurred in Japan, and where the incidence of this disease has increased sharply. METHODS: Data from the Reports of the Japanese Society for Cancer of the Colon and Rectum were used to analyze the time trend of colorectal cancer in Japan between 1974 and 1994 according to the patients’ age at diagnosis and sex, and the site of the tumor within the colon or rectum. RESULTS: The percentage of patients over the age of 70, especially females, increased. The increase in the percentage of right-sided colon cancer in colorectal cancer cases was accompanied by a continuous decline in the percentage of rectal cancer in both sexes at all ages. In general, the percentage of right-sided colon cancer in colon cancer cases was stable in men, but increased in women. The rate among patients older than 70 years increased in men, but predominated and remained stable in women. No proximal shift in colon cancer was found in either sex under the age of 69. CONCLUSION: These findings indicated that a proximal shift in the subsite distribution of colorectal cancer has occurred in Japan. This rightward shift of colorectal cancer is due to the decreasing proportion of rectal cancer. Furthermore, the increasing proportion of older patients, especially females, may be another major determinant of the changing colon cancer subsite distribution.

Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines.

Abstract Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 μM) with an IC50 of 7.0–274.2 μM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL-100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM–37 μM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 μM and EPA > 210.9 μM) and on MDA-MB-231 cells (genistein > 176.1 μM and EPA > 609.3 μM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.

Correlation of preoperative carcinoembryonic antigen levels and prognosis of gastric cancer patients

Background. The prognostic significance of preoperative serum carcinoembryonic antigen (CEA) determination in patients with gastric cancer has been controversial.

Cloning of a G‐protein‐coupled receptor that shows an activity to transform NIH3T3 cells and is expressed in gastric cancer cells

The present study was directed towards the identification of novel factors involved in the transformation process leading to the formation of gastric cancer. A cDNA library from human gastric cancer cells was constructed using a retroviral vector. Functional cloning was performed by screening for transformation activity in transduced NIH3T3 cells. Six cDNA clones were isolated, including one encoding the elongation factor 1asubunit, which was already known to play a role in tumorigenesis. One cDNA (clone 56.2), which was repeatedly isolated during the course of screening, encoded a protein identical to a G‐protein‐coupled receptor protein, GPR35. In addition, another cDNA clone (72.3) was found to be an alternatively spliced product of the GPR35 gene, whereby 31 amino acids were added to the N‐terminus of GPR35. Hence, the proteins encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively. RT‐PCR experiments revealed that GPR35 gene expression is low or absent in surrounding non‐cancerous regions, while both mRNAs were present in all of the gastric cancers examined. The level of 72.3‐encoded mRNA was consistently significantly higher than that of 56.2 encoded mRNA. An expression pattern similar to that observed in gastric cancers was detected in normal intestinal mucosa. Based on the apparent transformation activities of the two GPR35 clones in NIH3T3 cells, and the marked up‐regulation of their expression levels in cancer tissues, it is speculated that these two novel isoforms of GPR35 are involved in the course of gastric cancer formation.

Endocrine cells and prognosis in patients with colorectal carcinoma

Using chromogranin (CG) immunohistochemical staining, the prognostic significance of endocrine differentiation was investigated in 212 patients with primary colorectal adenocarcinoma (including 6 patients with mucosal carcinoma). CG‐immunoreactive cells were found to be an integral component of the tumor in 67 of 206 patients (32.5%, excluding mucosal carcinoma). The intra‐cellular localization of CG in the CG‐immunoreactive cells in cancer tissue was completely different from that in the normal endocrine cells of the large bowel. In addition, morphologic changes such as nuclear hyperchromasia and pleomorphism also indicated that the CG‐immunoreactive cells in the cancer tissue were malignant. The tumors were divided into three groups based on the frequency of CG‐immunoreactive cells: Group I (n = 139), negative; Group II (n = 38), less than 1 positive cell/mm2; and Group III (n = 29), more than 1 positive cell/mm2. No correlation was observed between CG‐immunoreactivity (CG‐IR) and tumor location, grade, depth of invasion, or stage, regardless of lymph node involvement. However, patients with numerous endocrine tumor cells (Group III) had a significantly worse prognosis compared with patients without endocrine cells (Group I) (multivariate Coxs model, P < 0.01). Similar findings were observed in patients with node‐negative tumor (multivariate Coxs model, P < 0.05). These results indicated that the neuroendocrine differentiation is an independent prognostic factor and that CG‐immunohistochemistry is useful for detecting a subgroup with a worse prognosis among patients with colorectal cancer.