Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer

PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995.     

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P <0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.Read at the meeting of the Japanese Society of Gastroenterological Surgery, Tokyo, Japan, February 24 to 25, 1994.     

Prognostic significance of location of lymph node metastases in colorectal cancer

The prognostic value of stage of lymph node metastases was evaluated in 357 patients who underwent curative resection for colorectal cancer. Subdivision of Dukes C patients according to the number of positive nodes revealed that the five-year disease-free survival rate (5DFS) was 63 percent in the patients with one to three nodes and 53 percent in those with four or more nodes (not significantly different). Classification according to the location revealed that 5DFS was 70 percent in those who had only local node metastases (n1+), compared with 40 percent in those who had distant node metastases along the major vessels (n2+) (P <0.001). Twelve of 38 n2+ patients had only one distant node metastasis with no local node involvement (skip metastasis). They had lower 5DFS than the n1+ patients who had three or more positive local nodes (35 percent vs. 57 percent). We conclude that the location, rather than the number, of nodal metastases has a higher impact on prognosis in colorectal cancer patients.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Does methodic long-term follow-up affect survival after curative resection of colorectal carcinoma?

Records of 487 patients in long-term follow-up after R₀ resection of colorectal carcinomas between January 1, 1980 and December 31, 1989 were analyzed. Every patient underwent regular examinations according to a defined schedule after curative resection of colorectal carcinoma. The date of evaluation was June 31, 1991. During a median observation time of 48 months (range, 15–132 months), tumor recurrence was observed in 149 patients (30.6 percent), with 56.4 percent of these suffering from tumor-associated symptoms. As the primary manifestation of tumor recurrence, only distant metastases (DM) were found in 76 patients (51 percent), only local recurrence (LR) in 46 patients (30.9 percent), and both DM and LR in 27 patients (18.1 percent). Patients with rectal carcinoma developed LR more frequently (P <0.05) (19.5 percent) than patients with colon carcinoma (11.8 percent). The probability of developing distant metastases was not different (P <0.05) for colon or rectal carcinoma but depended on primary tumor stage (P <0.05). Only 36 patients (24.2 percent) with recurrence could undergo further curative resection. Fifty patients (33.5 percent) were given palliative therapy, and 63 patients (42.3 percent) were given no oncologic treatment. Only 9 of the 36 patients (6 percent of all recurrence patients) undergoing R₀ resection were free of tumor for more than two years. In no case was a third R₀ resection possible. The survival time of these patients was increased significantly after R₀ resection of tumor recurrence (P =0.03). Our study suggests that only a very few patients may live longer as a result of regular follow-up programs after curative resection for colorectal carcinoma.     

Endosonography of pararectal lymph nodes

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz×cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz×cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.Supported by a grant from the Deutsche Forschungsgemeinschaft Hi 385/1-1     

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.     

Does concurrent splenectomy at colorectal cancer resection influence survival?

Twenty-one patients had a concurrent splenectomy with resection of colorectal cancer between 1970 and 1988. These were matched individually with disease control patients based on age, sex, site of tumor, Dukes stage, tumor differentiation, and date of the operation. Significantly more patients in the splenectomy group (n=11) developed postoperative infective complications than in the control group (n=4) (McNemar test: P =0.03). Five-year overall actuarial survival was 45 percent in the former group and 59 percent in the latter (log rank test: chi-squared=1.07;P =0.24). Similarly, five-year disease-free survival in 17 patients with Dukes B and C cancers who had curative resections did not differ between the groups (log rank test: chi-squared=0.08;P > 0.25). These results suggest that splenectomy with resection of colorectal cancer increases the risk of postoperative sepsis and does not influence long-term survival. The infrequency of concurrent splenectomy at resection of colorectal cancer may not overcome Type II error.     

DNA index as a significant indicator of lymph node metastasis and local recurrence of rectal cancer

To confirm the prognostic significance of the DNA index (DI) in cases of rectal cancer, the nuclear DNA content of tumor cells was examined in 184 cases of rectal cancer treated with curative surgery, and the incidence of lymph node metastasis and recurrence of the cancer was analyzed. The incidence of lymph node metastasis was 43.9 percent in cases with aneuploidy (DI above 1.5), being statistically different from the 18.0 percent incidence in cases with diploidy (P <0.001). Although the extent of lymph node metastasis was limited to adjacent lymph nodes in cases with diploidy, distant lymph node metastases were frequent in cases with aneuploidy, especially in those with a DI above 1.5. Furthermore, the incidence of recurrence of cancer, and especially of local recurrence, was significantly higher (P <0.001) in cases with aneuploidy (DI above 1.5) than in cases with diploidy and aneuploidy (DI below 1.4). These findings indicate the significant value of the DNA index for the prediction of lymph node metastasis and local recurrence in patients with rectal cancer.     

Predicting lymph node metastases in rectal cancer

For properly selected rectal cancers, local excision is a sphincter-saving alternative to abdominoperineal resection. If histologic assessment of a locally excised tumor reveals ominous features, further treatment with radical resection or irradiation may be necessary to treat potential lymph node metastases. PURPOSE: We wished to determine which features, if any, were predictors of nodal metastases. METHODS: Nine histologic and morphologic features of 62 radically excised rectal cancers were reviewed to determine which factors, if any, were associated with nodal disease. RESULTS: Using a chi-squared analysis, we found worsening differentiation (P=0.0001), increasing depth of penetration (P=0.026), a microtubular configuration of 20 percent or more (P=0.023), and the presence of venous (P=0.001) or perineural invasion (P=0.002) to significantly influence nodal disease. Lymphatic invasion was witnessed too infrequently to determine significance but, when present, was associated with nodal metastases in every case. Exophytic tumor morphology, mitotic count, and tumor size were not significant predictors. An analysis of variables determined that, of all factors or combination of factors examined, Broder's classification was the strongest predictor of nodal disease. CONCLUSIONS: If a rectal cancer is accessible and of small size to facilitate local excision, an in-depth histologic assessment is needed to determine if nodal metastases are likely on a statistical basis.This work was supported by the Bowman Research Fund.     

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.     

Relationship of apical lymph node involvement to survival in resected colon carcinoma

In a prospective study of 197 patients with resected colon carcinoma treated between 1974 and 1985, we explored the relationships between pathologic parameters, and the effect of the latter on survival, to identify the parameter whose systematic measurement would improve the predictive capacity of pathologic staging. Prognostic characteristics were studied by univariate analysis. The results showed significant relationships between the location and number of lymph nodes involved, blood vessel invasion, depth of tumor penetration, and metastases. The five-year survival rates were 45 percent and 17 percent (P < 0.001) for patients without and with apical lymph node involvement, respectively, and 44 percent and 6 percent (P <0.05) for those with four or less nodes involved and more than four involved, respectively. Among the patients treated by incomplete resection, the respective survival rates of those resected for metastases and of those resected for apical lymph node involvement did not differ significantly. We conclude that the involvement of apical lymph nodes has a significant effect on prognosis and suggest systematic pathologic examination of these nodes to allow simpler and more reproducible selection of patients for treatment by incomplete resection who are at high risk of disease-related death.     

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.     

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.     

Role of carcinoembryonic antigen and liver function tests in the detection of recurrent colorectal carcinoma

The optimal laboratory evaluation for the early detection of liver metastases from colorectal cancer is controversial. This investigation was undertaken to compare the efficacy of liver function tests (LFTs) with that of carcinoembryonic antigen (CEA) levels for the early detection of liver metastases. Patients who developed liver metastases after potentially curative resections of adenocarcinoma of the colorectum between 1974 and 1988 were reviewed. The following laboratory tests were serially evaluated during the follow-up period: CEA., alkaline phosphatase (AP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and lactic dehydrogenase (LDH). These values were retrospectively assessed from the time of documented liver metastases to identify which lab value (s) were elevated initially. Ninety-two patients were available for study. Average time for the occurrence of liver metastases was 20 months (range, 3–72 months). The incidence of elevation of individual tests at the time of suspicion of liver metastasis was: CEA, 94.6 percent (P <0.25, chisquared); AP, 18.5 percent; SGOT, 12.0 percent; SGPT, 5.4 percent; and LDH, 29.3 percent. When comparing CEA with a battery of LFTs at the time of suspicion of liver metastasis, CEA was elevated with normal LFTs in 64.1 percent (P <0.05, chi-squared), the most frequent occurrence. At least one LFT was elevated with a normal CEA in only 2.2 percent; CEA and at least one LFT were increased in 30.4 percent; and both tests were normal in only 3.3 percent. These results indicate that, of the individual laboratory tests performed, CEA elevation heralds liver metastases significantly more frequently. LDH is the liver function test most frequently elevated when liver metastases are first suspected. When CEA is directly compared with a battery of LFTs, CEA is statistically significantly more frequently elevated. In fact, suspicion of liver metastases would have been delayed by the omission of LFTs in only 2.2 percent of patients. Therefore, we conclude that LFTs should be deleted from the follow-up of colorectal cancer patients, decreasing costs without significantly decreasing accuracy.     

Escherichia coli heat-stable enterotoxin receptors

PURPOSE: Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro,suggesting their use as a marker for colorectal tumors in vivo.The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. METHODS: Surgical specimens were obtained as follows: from normal colon; from primary adenocarcinomas from all anatomic divisions of the colon and rectum; from gallbladder, kidney, liver, lung, lymph node, ovary, peritoneum, stomach; and from colon carcinomas metastatic to liver, lung, lymph node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. RESULTS: ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation of guanylyl cyclase was detected in any extraintestinal tissues examined. CONCLUSIONS: Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not by extraintestinal tissues in humans. Expression of ST receptors does not vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase. These studies support the suggestion that ST receptors represent a specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.Supported, in part, by grants from the National Science Foundation (IBN-9205717), the National Institutes of Health (1 R55 DK43805), the Elsa U. Pardee Foundation, and Targeted Diagnostics and Therapeutics, Inc. Stephen L. Carrithers was the recipient of a National Institutes of Health Postdoctoral Fellowship (1 F32 CA63764-01).Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Primary signet-ring cell carcinoma of the colon and rectum

PURPOSE: Colorectal signet-ring cell carcinoma (SRCC) is uncommon; discordant data have been previously reported about clinicopathologic features. Thirty-four cases of primary colorectal SRCC were retrospectively reviewed to clarify controversies. METHODS: Primary colorectal SRCC was diagnosed when the following criteria were satisfied: 1) the tumor was primary; 2) histologic material was adequate; 3) signet-ring cell represented more than 50 percent of the cancer. RESULTS: We identified 34 cases (1.1 percent) of 2,995 consecutive large bowel cancers collected at the Institute of Anatomic Pathology of Florence between 1985 and 1993. Patients ranged in age from 31 to 89 (mean, 63.5; median, 65) years; 19 were male, and 15 were female (male:female=1.31). Fifteen tumors were located in the proximal colon, 11 in the rectum, and 8 in the distal colon. The gross shape was infiltrative in 24 cases and exophytic in 10; only 6 cases (17.6 percent) showed features of linitis plastica. Most cancers (61.8 percent) were Stage C, 29.4 percent were Stage B, and distant metastases were present in only three cases (8.8 percent). No Stage A case was found. Prognosis was extremely poor, and overall five-year survival rate was 9.1 percent. Survival was influenced significantly by tumor stage (P <0.01). CONCLUSIONS: Comparison of our data with the literature showed many differences that could be related to different applied diagnostic criteria. We underlined the importance of histology as reproducible criterion for diagnosis of primary colorectal SRCC.     

Colorectal adenocarcinoma: Quality of the assessment of lymph node metastases

PURPOSE: We have studied 193 cases of colorectal adenocarcinoma from a population-based register to determine the minimum number of lymph nodes to be examined to provide an accurate assessment of the presence of nodal metastases. METHODS: The mean total number of lymph nodes identified per surgical specimen was 11 ±6.8 (range, 1–36) using traditional dissection. One hundred eighteen specimens (61 percent) were classified as Dukes B. Seventy-five (39 percent) had lymph node metastases (Dukes C) with a mean of 3.3±4.7 positive lymph nodes per specimen. With binomial distribution we calculate the probability to find at least one positive node in a sample size n with a determined proportion of positive nodes. RESULTS: The error probability in the ganglionar assessment by traditional dissection was 0.05 with 6 examined lymph nodes and 0.01 with 10 examined nodes. CONCLUSION: We must provide the pathologist with a minimum of six examined lymph nodes per surgical specimen for an optimal Dukes B assessment.Read at the XIX National Congress of The Spanish Society of Surgeons, Madrid, Spain, November 9 to 13, 1992.     

Resection of liver metastases from colorectal cancer

PURPOSE: This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS: From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS: Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P=0.01). CONCLUSIONS: Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure.     

Correlation between macroscopic morphologic features and malignant potential of colorectal sessile adenomas

PURPOSE AND METHODS: To clarify malignant potential of colorectal sessile adenomas, we investigated 46 colorectal sessile adenomas surgically resected from 44 patients. Lesions were divided into three types according to their macroscopic morphologic features: nodular-type (19 adenomas), villous-type (7), and creeping-type (20). Clinicopathologic features were investigated and compared among these three types. RESULTS: Frequency of focal carcinoma in the nodular-type, villous-type, and creeping-type adenoma was 37, 29, and 55 percent, respectively. Frequency of submucosal invasion in these three types were 11, 14, and 20 percent, respectively. Irrespective of the type, large lesions (>3 cm) tended to have a higher frequency of submucosal invasion than did smaller ones (60 vs. 20 percent; P =0.063). Large creeping-type adenomas (>3 cm) had a definitely higher frequency of submucosal invasion than smaller ones (36 vs. 0 percent; P <0.05). Lymphatic or vascular invasion of carcinoma was present only in the lesion with submucosal invasion: 5 percent in the nodulartype; 14 percent in the villous-type; 20 percent in the creeping-type. Lymph node metastasis was present only in the creeping-type lesion. CONCLUSIONS: The large creeping-type adenomas (>3 cm) have a definitely high frequency of submucosal invasive carcinoma. Endoscopic polypectomy or local resection may be adequate for most sessile adenomas. However, we recommend segmental resection of the colon with regional lymph node dissection for a creeping-type adenoma that is larger than 3 cm because of increased risk of submucosal carcinomatous invasion and lymph node involvement.Presented in part at the meeting of the Japan Society of Coloproctology in Yokkaich, Japan, November 26 to 27, 1994.     

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.