Effect of octreotide on anal pressure and rectal compliance

PURPOSE: The somatostatin analog, octreotide, has previously been found to influence rectal sensation and may also influence anal resting pressure. METHODS: We studied the effect of octreotide on anal resting pressure and rectal compliance in eight healthy patients. Octreotide was administered intravenously as a bolus injection in doses of 100 and 10 g or as infusion of 250 g/ hour on separate days and compared with placebo. RESULTS: Within one minute after a bolus injection of 100 g of octreotide, anal resting pressure increased from 56±12 to 96±16 cm H ₂ O (P<0.005). Octreotide had no effect on rectal sensitivity or compliance measurements. Octreotide counteracted rectoanal reflex by increasing anal pressure almost to the level found with an empty rectum. CONCLUSION: Somatostatin thus seems to contribute to the regulation of rectoanal reflex.     

Anti-tumor × anti-lymphocyte heteroconjugates augment colon tumor cell lysisin Vitro and prevent tumor growthin Vivo

Cross-linking an anti-tumor antibody, specific for tumor cell surface antigens, and an anti-lymphocyte antibody, specific for the T lymphocyte receptor complex (TCR/ CD3), produces a heteroconjugate that can direct T cells to lyse tumor cells. We tested the ability of anti-tumor × anti-lymphocyte (CD3) heteroconjugates to redirect human peripheral blood lymphocytes (PBLs) to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model. We demonstrated in vitro,that cultured human PBLs alone produced low levels of tumor lysis, but PBLs treated with anti-tumor × anti-CD3 heteroconjugates produced significantly greater tumor cell lysis (P<0.0025). Similarly, nude mice injected with LS174T human colon cancer cells and treated with cultured human PBLs and anti-tumor × anti-CD3 heteroconjugates survived significantly longer than saline control mice (P<0.01), or mice treated with PBLs alone (P<0.01), or heteroconjugates alone (P<0.05). F(ab) ₂ heteroconjugates were equally as effective in prolonging animal survival, but irrelevant heteroconjugates and monoclonal anti-tumor antibodies showed no therapeutic benefit. Anti-tumor × anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29–May 4, 1990. Dr. Nelson was supported by the Leon Hirsch Traveling Scholarship, awarded by the Research Foundation of The American Society of Colon and Rectal Surgeons. This material was acknowledged with a research award from the New England Society of Colon and Rectal Surgeons. Dr. Donohue is the recipient of a Cancer Development Award from the American Cancer Society.     

Suppression of the growth of human colorectal carcinoma cells (LS174T) by radiolabeled monoclonal antibody (131I-MAbC27) in tissue culture and nude mice

A monoclonal antibody against carcinoembryonic antigen (CEA), MAbC27, and its F(ab′)₂ fragments were prepared and labeled with¹³¹I. They effectively suppressed the growth of a human colorectal carcinoma cell line, LS174T, both in culture medium and in inoculated nude mice, whereas¹³¹I-labeled normal mouse immunoglobulin or¹³¹I itself did not have similar effects. Intravenous injection of¹³¹I-MAbC27 or¹³¹I-MAbF(ab′)₂ following inoculation of carcinoma cells suppressed their growthin vivo. The suppression effect was even more effective when intact antibody rather than its F(ab′)₂ fragments was used, especially when the treatment was repeated. This study indicates that radiolabeled MAbC27 may be used as a therapeutic agent in CEA-secreting human colorectal carcinomas.     

Sulphonylurea stimulates glucose uptake in rats through an ATP-sensitive K+ channel dependent mechanism

Summary We studied the effect of gliclazide, a second-generation sulphonylurea, on rat skeletal muscle glucose uptake using perfused hindquarter muscle preparations. Gliclazide at concentrations of 10 to 1000 g/ml increased (p<0.05) the basal glucose uptake. The effect of gliclazide on glucose uptake was immediate and dose-dependent, reaching a plateau at a concentration of 300 g/ml; the half-maximal effect was obtained between 25 and 50 g/ml. The glucose uptake stimulated by gliclazide (300–1000 g/ ml) did not differ from that achieved by 10^–9 mol/l insulin, and was lower (p<0.05) than that obtained with 10^–7 mol/l insulin. The combination of gliclazide (300 g/ml) and 10^–9 mol/l insulin produced an increase in glucose uptake (7.7±0.6 mol · g^–1 · h^–1, n=8, mean±SEM) which was higher (p<0.05) than that achieved with 10^–9 mol/l insulin (5.6±0.7 mol · g^–1 · h^–1, n=11) and not different from that obtained with 10^–7 mol/l insulin (9.8±1.0 mol · g^–1 · h^–1, n=11). Diazoxide (100 mol/l), an ATP-sensitive K⁺ channel opener, reversed the stimulatory effect of gliclazide (100 g/ml) on muscle glucose uptake from 3.1±0.4 to 0.5±0.2 mol · g^–1 · h^–1, (n=7, p<0.001). The addition of diazoxide prior to gliclazide into the perfusion medium blocked the gliclazide-induced glucose uptake by the hindquarter muscle preparations. In conclusion, gliclazide alone has an immediate stimulatory effect on glucose uptake by skeletal muscle and together with insulin has an additive effect on muscle glucose uptake. The effect of gliclazide on muscle glucose uptake seems to be due to the inhibition of ATP-sensitive K⁺ channels.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - GLUT glucose transporter     

Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13-acetate and mezerein on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene

Summary Cepharanthine, isolated fromStephania cepharantha, is one of the bisbenzylisoquinoline-type alka-loids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 g/mouse) and mezerein (5 g/mouse) were found to be inhibited by topical application of cepharanthine, with a ED₅₀ of 1.2 mol and 1.4 mol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse^– day^–) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 g TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 g mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 g 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.Abbreviations DMBA 7,12-dimethylbenz[a]anthracene - DTH delayed-type hypersensitivity - ODC ornithine decarboxylase - TPA 12-O-tetradecanoylphorbol 13-acetate     

Plasma and urine free L-Carnitine in human diabetes mellitus

Summary L-carnitine is essential for the transport of long-chain fatty acids into mitochondria and their oxidation. Recently, a relationship between plasma free fatty acids (FFA) and L-carnitine metabolism has been observed. Plasma free L-carnitine (FC), FFA, triglycerides, cholesterol, blood glucose concentration and daily excretion of FC were determined in 20 diabetic patients as well as in 18 control subjects. Both in male diabetics and in male controls, plasma FC was significantly higher than in females. Mean plasma FC was found to be significantly reduced in diabetics (21 ± 2vs 35 ± 2 mol/1 in non-diabetic subjects; p<0.005). Daily urinary excretion of FC was clearly lower in diabetic patients than in controls (172 ± 34vs 403 ± 38 mol/24 h; p<0.001). The reduced plasma FC in diabetes mellitus may be due to redistribution between circulating free and esterified carnitine and to increased utilization of FC for synthesis of acylcarnitine in tissues.     

B72.3 Immunoreactivity in benign abdominal lymph nodes associated with gastrointestinal disease

PURPOSE: Immunolocalization of the tumor-associated glycoprotein 72 antigen with the monoclonal antibody B72.3 has been used as a cancer marker in radioimmunoscintigraphy and radioimmunoguided surgery (RIGS). Radioimmunoscintigraphy and RIGS have been used to detect occult metastatic deposits from colorectal adenocarcinoma. It has been suggested that RIGS is superior to histologic examination in detecting lymph node metastases from colorectal cancer. To determine the specificity of immunodetection of the tumor-associated glycoprotein -72 antigen as a marker for metastatic adenocarcinoma, we studied benign intraabdominal lymph nodes with B72.3 and an immunohistochemical technique. METHODS: Formaldehyde-fixed, paraffin-embedded sections of 276 benign abdominal lymph nodes, resected with 35 cases of colonic adenocarcinoma and 33 cases of benign gastrointestinal disorders, were evaluated for B72.3 immunoreactivity using an avidin-biotin complex immunohistochemical technique. Lymph nodes from cases of colonic carcinoma were also studied with cytokeratin immunostaining to help eliminate occult micrometastases. RESULTS: B72.3 immunoreactivity was seen in the germinal centers of benign lymph nodes associated with 49 percent of the cases of colonic adenocarcinoma and 12 percent of the cases of benign gastrointestinal disease. CONCLUSIONS: B72.3 immunoreactivity can be seen in benign abdominal lymph nodes associated with gastrointestinal disease. We advise caution in the use of diagnostic techniques that equate B72.3 immunoreactivity with the presence of adenocarcinoma.Read at the meeting of the United States and Canadian Academy of Pathology, Toronto, Ontario, Canada, March 11 to 17, 1995.     

Level of serum gastrin as a predictor of liver metastasis from colorectal cancer

There have been no reports on the relationship between serum gastrin level and liver metastasis in human colorectal cancer. One hundred forty patients who underwent surgery for colorectal cancer (T2 or more) were enrolled in this study. Fasting serum gastrin level was determined prior to the surgery. Incidence of liver metastasis was significantly (P<0.01) higher in patients with a serum gastrin level of 150 pg/ml (37 percent; 14/38) than in those with a serum gastrin level of <150 pg/ml (12 percent; 12/102). As for the tumors with venous invasion, liver metastasis was detected in 11 of 55 patients (20 percent) with a serum gastrin level of <150 pg/ml; however, it was detected in 11 of 19 patients (58 percent) with a serum gastrin level of 150 pg/ml (P<0.01). These results suggest that serum gastrin serves as a useful predictor of liver metastasis from colorectal cancer and that the predictability of liver metastasis can be improved when both serum gastrin level and venous invasion are considered.     

Should HIV status alter indications for hemorrhoidectomy?

PURPOSE: There is a widespread belief that performing hemorrhoidectomy on a patient infected with human immunodeficiency virus (HIV) is an invitation for disaster. Aim of this study was to compare morbidity of hemorrhoidectomy in HIV-positive (HIV+) with HIV-negative (HIV–) patients. METHODS: Charts of 27 HIV+ and 30 HIV–male patients less than age 50 years who underwent hemorrhoidectomy were reviewed. RESULTS: Mean age of the 57 study group patients was 38 years. Open hemorrhoidectomy was performed in 26 patients (46 percent), and a closed technique was used in 31 patients (54 percent). HIV+ and HIV–patient groups were well matched to all preoperative and intraoperative variables. Mean T-cell helper count in the HIV+ patient group was 301 (range, 9–1,040) cells/l. There were no deaths, and complications were seen in 15 patients (26 percent). There was no difference in overall complication rates between HIV+ and HIV–patient groups. Urinary retention was seen in ten patients (18 percent), three of whom were HIV+ (11 percent) vs. seven of whom were HIV -(23 percent) (P=not significant). Although no patient required reoperation for bleeding, postoperative hemorrhage was seen in three patients (1 HIV+, 2 HIV -). None of the patients developed fecal incontinence. Mean time to complete wound healing was 6.8 (range, 4–12) weeks for HIV+ patients vs. 6.6 (range, 4–14) weeks for HIV–patients (P=not significant). CONCLUSIONS: These data suggest that HIV status of a patient should not alter indications for surgical management of hemorrhoidal disease.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Prognostic relevance of occult tumor cells in lymph nodes of colorectal carcinomas

PURPOSE: Whereas lymph node metastases in colorectal carcinoma are an important prognostic factor, the prognostic relevance of occult tumor cells in lymph nodes is not elucidated at present. Therefore, our study intended to assess the rate of patients with occult tumor cells in histopathologically negative lymph nodes. Furthermore, we tried to evaluate an eventual influence of these occult tumor cells on patients' prognoses. METHODS: For examination, we used paraffin blocks of lymph nodes, tumor-negative by conventional histopathology, from 49 patients with colorectal carcinoma (Stage I–III) after a curative (RO) tumor resection in 1987. After preparation of tissue blocks using the serial sectioning technique, the specimens were stained with the alkaline phosphatase, antialkaline phosphatase method and two monoclonal antibodies (AE1/AE3 and Ber-EP4). RESULTS: In 13 of 49 patients (26.5 percent), we disclosed tumor cells, mostly located in subcapsular sinuses as single cells or in groups. There was a good correlation between the detection rate and N category, tumor stage, and grading. Moreover, 33 percent of patients in Stage I/II with occult tumor cells (NO+) developed a local relapse and/or distant metastases in contrast to 12 percent of patients without tumor cells (NO–). With a median follow-up of 84 months, we found no difference in disease-free survival between the tumor cell negative and positive groups in Stage I/II patients. CONCLUSION: The results show that occult tumor cells might increase the risk for development of a local tumor relapse and/or distant metastases but do not influence patients' prognoses at all.Presented at the Walter Brendel Prize Session of the XXXIst Congress of the European Society for Surgical Research, Southampton, United Kingdom, March 31 to April 3, 1996.     

Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7

Summary The effects of toremifene, a new antiestrogenic drug, were investigated in vitro on the exponentially growing human mammary carcinoma cell line MCF-7. The drug effects were monitored by serial cell counts and DNA flow cytometry. The inhibitory effect of toremifene on MCF-7 became greater as the drug concentration was increased from 1 M to 10 M. At 5 M toremifene induced a large decrease in the relative percentages of Sand G2/M-phase cells, and an increase in the amount of cell debris, indicating increased cell death. After withdrawal of the drug the mammary cancer cells resumed logarithmic growth similar to that of control cells. The effects caused by toremifene were similar to those caused by tamoxifen both in quality and quantity.Abbreviations ER estrogen receptor - D5 growth medium containing 5% fetal bovine serum depleted of steroids - TGF transforming growth factor The study was supported by the Cancer Society of Finland     

Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis

PURPOSE: Recognition of metastatic tumor cells with distinct biochemical phenotypes predominant in the primary tumors should be useful not only for establishment of new therapeutic approaches but also for identification of highrisk or low-risk patients for relapse. We examined whether carbohydrate antigens, sialyl Lewis^x (sLe^x) and sialyl Lewis^a (sLe^a) are involved in colorectal cancer metastasis. METHODS: Metastatic abilities of human colon cancer cell variants that were selected for their high or low cell surface levels of sLe^x (KM12-HX and KM12-LX, respectively) were analyzed. Also, immunohistochemical expressions of sLe^x and sLe^a in 159 primary colorectal cancers were examined to determine the clinical significance of increased expression of these antigens. RESULTS: KM12-HX cells adhered more readily to tumor necrosis factor- activated endothelial cells than did KM12-LX cells. Increased adhesion of KM12-HX cells to activated endothelial cells was inhibited by antibodies against E-selectin and sLe^x and by modification of cell surface carbohydrates. KM12-HX cells showed more invasive ability in vitro and more metastatic potential in the liver of nude mice than KM12-LX cells. Although no difference was seen in the expression of six messenger ribonucleic acids corresponding to progression or metastasis of colorectal cancer, expression of fucosyltransferase was found to be responsible for the higher expression of sLe^x in KM12-HX cells. Clinical records of patients showed that disease-free survival rate of patients with sLe^x-positive tumors was significantly poorer than that of those with sLe^x-negative tumors. Cox's multivariate analysis revealed that the sLe^x status was an independent predictive factor for disease recurrence (P = 0.004), depth of invasion (P = 0.0005), and histologic type> (P = 0.037), but sLe^a status, age, gender, tumor location, N stage, and vessel invasion were not. CONCLUSION: Increased expression of sLe^x could be involved in establishment of colorectal cancer metastasis. It appears that examining sLe^x expression may serve as a potent marker of the recurrence in patients with colorectal cancer.Supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, Japan. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria

Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (<15 /min) and 16 with microalbuminuria (15–200 g/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p=0.27). The tissue was sectioned systematically, 1-m thick sections for light microscopy at 10-m intervals, and thin sections for electron microscopy taken at 60-m intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500×), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p=0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p=0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) m vs 1.44 (0.30) m (p=0.004), and 1.62 (0.28) m vs 1.03 (0.34) (p=0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.Abbreviations IDDM Insulin-dependent diabetes mellitus - GFR glomerular filtration rate - AER albumin excretion rate - matrix-T matrix thickness - ND non-diabetic subjects - D_NA IDDM patients with normal albumin excretion rate - D_MI IDDM patients with microalbuminuria - RPF renal plasma flow - CV coefficient of variation     

Variable expression of P-glycoprotein in normal,inflamed, and dysplastic areas in ulcerative colitis

Screening programs for the detection of cancer in ulcerative colitis are inexact and not always successful in finding early, curable cancers. P-glycoprotein is a membrane-based, energy-dependent protein found in varying degrees within normal human tissue. P-glycoprotein is overexpressed in malignant tumors, particularly colorectal cancer, and is known to convey resistance to certain anticancer drugs by acting as a membrane pump. The purpose of this study was to determine the expression of this protein in inflamed and premalignant colonic epithelium, compare its expression with normal controls, and assess its potential use as a screening tool for high-risk patients with ulcerative colitis. Using immunohistochemical techniques, the colons of 21 patients (10 with dysplasia) with ulcerative colitis were stained with monoclonal antibody C-219 (MAbC219) specific for P-glycoprotein. P-glycoprotein was expressed in 38 percent of normal areas, 71 percent of inflamed areas (P =0.0156), and 70 percent of dysplastic areas. Comparing the level of expression when progressing from normal to inflamed areas within a given patient, 11 patients (52 percent) showed increased expression, 8 (38 percent) showed equal expression, and only 2 (10 percent) showed decreased expression (P =0.0225). Comparing expression when progressing from inflamed to dysplastic areas (10 patients), 7 showed equal expression and 3 showed increased expression (P =0.25). Increasing duration of disease was associated with a significant increase in P-glycoprotein expression, but only in histologically normal areas. Duration of disease had no effect on P-glycoprotein expression in inflamed or dysplastic areas. Similarly, when surgery was performed for elective reasons, there was a significant overexpression of P-glycoprotein, but only in histologically normal areas. Our findings suggest that the increase in P-glycoprotein expression from normal to inflamed and dysplastic areas reflects the premalignant nature of ulcerative colitis and occurs early in the course of the disease. Further research needs to be done to determine its role in cancer surveillance.Presented at the meeting of the American College of Gastroenterology, Boston, Massachusetts, October 14, 1991.This work was supported in part by the Bowman Research Fund.     

Long-term results of curative resection of “minimally invasive” colorectal cancer

PURPOSE: The aim of this study was to determine the long-term outcome after curative resection of colorectal cancers that extend only into the submucosa (minimally invasive) and to evaluate potential histologic predictors of lymph node metastases. METHODS: Seventy-nine patients who underwent curative resection of minimally invasive colorectal cancer and were followed for at least five years were studied retrospectively. RESULTS: The series was comprised of 53 men and 26 women, with a mean age of 61 years. The lesion was in the colon in 47 patients and the rectosigmoid or rectum in 32 patients. Open surgery followed attempted endoscopic tumor removal in 25 patients. Lymph node metastasis, found in 11/79 patients (13.9 percent), was associated with worse outcome: 36.4 percent of node(+) patients developed recurrence,vs. only 5.9 percent of node(–) patients (P <0.005). The cumulative survival rate was also worse in node(+) vs. node(–) patients: 72.7 percent vs. 91.1 percent at five years (P <0.05) and 45.5 percent vs. 65.3 percent at ten years (P <0.05). Five histopathologic characteristics were identified as risk factors for lymph node metastasis: 1) small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion (tumor budding); 2) a poorly demarcated invasive front; 3) moderately or poorly differentiated cancer cells in the invasive front; 4) extension of the tumor to the middle or deep submucosal layer; 5) cancer cells in lymphatics. Whereas patients with three or fewer risk factors had no nodal spread, the rate of lymph node involvement with four or more risk factors was 33.3 percent and 66.7 percent, respectively. CONCLUSIONS: Metastasis is not infrequent in minimally invasive colorectal cancer. Appropriate bowel resection with lymph node dissection is indicated if such a lesion exhibits more than three histologie risk factors for metastasis.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Adhesive function of carcinoembryonic antigen in the liver metastasis of KM-12c colon carcinoma cell line

PURPOSE: Both experimental and clinical results reveal that carcinoembryonic antigen (CEA) seems to mediate some important role in the liver metastasis of colorectal carcinoma cells. The intent of this study was to verify whether adhesive function of CEA might affect liver metastasis in the CEA-expressing colon carcinoma cell line, KM-12c. METHODS: The hepatic binding of [¹²⁵I]iododeoxyuridine KM-12c cells was measured with or without intravenous CEA pretreatment in four nude mice each. Then, 2×10⁶ cells of KM-12c were injected into the splenic subcapsule of 57 CEA-pretreated nude mice. KM-12c cells were prepared in phosphate-buffered saline (control, 27 mice) or anti-CEA monoclonal antibody, T84.66 (30 mice). All mice were killed at the end of the eighth week after implant, and tumor nodules were confirmed histologically. RESULTS: Marginal differences of hepatic sequestration were found between the CEA-pretreated mice and the control group. Splenic tumor occurred in 75 percent (18/24) of the control group and in 40 percent (10/25) of the T84.66-pretreated group (P=0.0107). Forty-two percent (10/24) incurred liver metastasis in the control group, whereas 20 percent (5/25) did so in the T84.66-pretreated group. The number of splenic tumor cells was significantly related to the number and volume of liver metastasis (P=0.0065). CONCLUSIONS: CEA enhanced liver metastasis predominantly by successful primary tumor implant, whereas primary hepatic entrapment also supported it to some extent in a weakly metastatic colon carcinoma cell line, KM-12c. Tumor cell aggregates seem to be mediated by homophilic binding of CEA molecules, and it is an important mechanism to yield liver metastasis.Supported by Asan Foundation Grant, 1996–1997, Asan Institute for Life Sciences, Seoul, Korea.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Clinical significance of ras p21 overexpression for patients with an advanced colorectal cancer

The expression of ras oncogene product p21 was examined in 45 paraffin-embedded sections of primary advanced colorectal cancers, using the anti-v-H-ras p21 monoclonal antibody Y13-259. Fourteen of these specimens (31 percent) were stained positively. The incidence of lymphatic vessel invasion of cancer cells and lymph node metastasis correlated statistically with the overexpression of ras p21. The depth of invasion and incidence of liver metastasis in the p21-positive group were more prominent than in the p21-negative group. Statistically significant differences were evident in operative curability and clinical stage at initial surgery and in the longterm survival rate between these groups (P <0.05). We propose that ras p21 overexpression may serve as a marker to predict the prognosis of colorectal cancer.     

Value of carcinoembryonic antigen in the management of colorectal cancer

PURPOSE: The practical value of carcinoembryonic antigen (CEA) assay in the management of colorectal cancer after surgery is controversial. The value of CEA in the management of colorectal cancer was reviewed and discussed to justify the use of CEA assay in the management of colorectal cancer. METHODS: A retrospective study was performed on 318 patients who underwent resection by one surgeon (JYW) between 1981 and 1986 and who were followed for a minimum of 5 years or until death. RESULTS: The incidence of preoperative CEA levels >5 ng/ml in Dukes Stages A, B, C, and D were 0, 32, 48, and 79 percent, respectively. Five-year survival rates for groups with CEA levels 5 ng/ml and >5 ng/ml were 85 percent and 55 percent (P < 0.05), respectively, in Dukes Stage B patients and 64 percent and 37 percent (P < 0.05) in Stage C patients. The sensitivity and specificity of postoperative CEA monitoring in detecting recurrent diseases were 66 percent and 94 percent, respectively, for patients with a preoperative CEA value 5 ng/ml and 97 percent and 88 percent for patients with a higher preoperative CEA value. CONCLUSION: CEA is still the best tumor marker available to be used as an independent prognostic factor and as a monitor for recurrence of disease after primary tumor resection.     

Neuroendocrine cancers of the colon and rectum

PURPOSE: Our goal was to define the incidence of neuroendocrine carcinomas of the colon and rectum, the patterns of neuroendocrine expression, and the cellular subtype within neuroendocrine tumors. We attempted to determine whether differences in neuroendocrine expression or specific cell type influenced survival. METHODS: Over a ten-year period, 988 patients had resections for colorectal cancer. Using immunohistochemical staining methods specific for neuroendocrine markers, 39 (3.9 percent) neuroendocrine cancers were identified retrospectively. Tumors were also stained with monoclonal antibody A-80 which is specific for exocrine differentiation. In this way we were able to determine the extent of neuroendocrine differentiation such as pure neuroendocrine, predominant neuroendocrine, and equal neuroendocrine-exocrine expression. RESULTS: Average patient age was 65.5 (range, 28–89) years; there were 25 males and 14 females. Nineteen tumors were located in the right colon, 11 in the left, and 9 were in the rectum. Three histopathologic patterns were identified: pure neuroendocrine (n=11), predominantly neuroendocrine (n=17), and cancers with equal exocrine and neuroendocrine differentiation (n=7). Three cellular subtypes were seen: small-cell (n=15), intermediate-cell (n=15), and well-differentiated neuroendocrine cancers (n=5). There was one Dukes A cancer, 7 Dukes B, 16 Dukes C, and 15 patients had metastases to distant sites at the time of diagnosis. As a group, neuroendocrine tumors have a poor prognosis: six-month survival was 58 percent, three-year survival was 15 percent, and five-year survival was 6 percent. Survival statistically correlated with tumor stage (P=0.01) but not with age, sex, tumor location, histopathologic pattern, or neuroendocrine subtypes. Median survival for pure neuroendocrine carcinomas was seven months and for predominantly neuroendocrine carcinomas was five months. Tumors with equal neuroendocrine and exocrine differentiation had a median survival of 22 months (P=0.3). Small-cell neuroendocrine carcinomas had a median survival of five months, intermediate-cell had 11 months, and well-differentiated had a median survival of 22 months (P=0.1). CONCLUSIONS: Neuroendocrine differentiation is found in at least 3.9 percent of colon and rectal cancers. Many of these tumors were initially diagnosed as carcinoids, the diagnosis was changed to neuroendocrine carcinoma after immunohistochemical staining. Overall survival is poor especially for small-cell and pure neuroendocrine carcinomas.Supported by the Bowman Research Fund, Chicago, Illinois.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

What is the meaning of colorectal transit time measurement?

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P < 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P < 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P <0.001). This may explain why a large percentage of constipated patients have been found by most authors to have normal colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.