Outcome of local excision for locally invasive rectal carcinomas with special reference to histological features at the invasive margin

BACKGROUND: Several researchers reported promising results that local excision with or without postoperative chemo-radiation therapy is an alternative approach for sphincter preservation in patients with locally invasive rectal carcinomas. However, indications and long-term results have not yet been determined. METHODS: Demographic and pathological characteristics of eight patients with locally invasive tumors undergoing initially local excision were reviewed with reference to histological features at the invasive margin. RESULTS: All the tumors were well differentiated adenocarcinomas. In all but two tumors, the invasion was limited within the proper muscle layer. Radiation therapy was given preoperatively in one patient and postoperatively in two patients. Additional bowel resection was not attempted in these three cases. Among the remaining five patients, two received additional bowel resection with lymph node dissection. No lymph node metastasis was observed in these two patients. During the average follow-up period of 55 months, three patients had regional lymph node metastases at 7, 36 and 72 months, respectively. Another patient had regional lymph node and distant metastases at 5 months. Three out of five patients with moderate to severe grade of dedifferentiated histology at the invasive margin (H-inv) had regional lymph node metastases. On the other hand, one out of three patients with mild H-inv had lymph node metastases. CONCLUSIONS: H-inv may be useful as a clinical predictor of lymph node metastasis. However, more experience is needed to confirm the usefulness of H-inv in selecting invasive rectal cancer patients in whom local excision is safe and appropriate.      

Prediction of invasive activities in hepatocellular carcinomas with special reference to alpha-fetoprotein and des-gamma-carboxyprothrombin

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the world's major malignancies, especially in Asian countries. To improve the prognosis of HCC, it is essential to predict its invasive behavior in both intra- and extra-hepatic modalities. For this purpose, we examined the predictive values of two tumor markers, alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP). METHODS: 194 HCC cases at the National Cancer Center Hospital were selected from the Pathology Records. Detailed information regarding the existence of extra-hepatic venous invasion (EHVI) at the portal vein and intra-hepatic multiple malignant tumors (IHMTs) were collected and combined with the preoperative AFP and DCP testing results. Furthermore, information about the viral infection status such as HBs antigen positive or HCV antibody positive or no viral hepatitis was obtained. The information was analyzed by the ROC (Receiver Operating Characteristic Curve) method. RESULTS: and Conclusions: In both the EHVI group and the IHMT group, all the combinations except the HCV-positive group of IHMT revealed a tendency for DCP to offer better diagnostic accuracies, although this was statistically significant only in the HBs-positive group of IHMT. This result indicates either (1). that in a strict sense, DCP is not necessarily better than AFP at predicting the invasive characteristics or (2). that DCP is better than AFP at reflecting the invasive characteristics of HCC although not statistically significant. In either situation, from a long-term viewpoint, it is advisable to find a new marker or to re-evaluate the existing markers in order to predict the invasive characteristics more accurately.     

Expression of Beta-1 integrin in human gastric carcinomas - correlation with histological type and tumor progression

The expression of beta1 integrin, a subunit of cell adhesion receptor molecules, in human gastric carcinomas was examined by Northern blotting, Western blotting and immunohistochemistry. All the five gastric carcinoma cell lines expressed beta1 integrin mRNA and protein. Among them, TMK-1 cells expressed abnormal beta1 integrin protein with lower molecular weight. In gastric carcinoma cases, all the tumor tissues as well as corresponding non-neoplastic gastric mucosa expressed beta1 integrin mRNA and protein at various levels. Poorly.differentiated adenocarcinomas, especially Borrmann's type-4 or scirrhous carcinomas where the tumor cells proliferate diffusely with productive fibrosis, expressed beta1 integrin at higher level when compared to well differentiated adenocarcinomas. The level of beta1 integrin expression increased as the tumor stage progressed. Deeply invasive carcinomas showed a tendency to express beta1 integrin at higher level. These findings suggest that beta1 integrin might be an important determinant of development of scirrhous carcinoma and implicated in the invasive growth and the progression of gastric carcinomas.     

Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.     

Antitumor activity of cisplatin and carboplatin against human tumor xenografts serially transplanted into nude mice--with special reference to gastric carcinomas

Experimental chemotherapy with cisplatin and carboplatin was performed against nine human tumor xenografts serially transplanted into nude mice. Tumors used for the experiment were seven gastric (St-4, St-15, St-40, H-111, SC-2-JCK, SC-6-JCK and Exp-4), one breast (MX-1) and one colon (Co-4) carcinomas. Cisplatin 9 mg/kg and carboplatin 100 mg/kg were administered intraperitoneally (ip). Carboplatin 25 mg/kg was also given ip 4 times every 4 days. The efficacy rates of cisplatin and carboplatin by bolus injection were 77.8% and 66.7% respectively with no statistically significant differences. However, carboplatin was found more effective when given by bolus. The antitumor spectra of both drugs were similar. From these results, these two platinum compounds seemed to be effective against human gastric carcinomas.     

The role of myofibroblasts at the tumor border of invasive colorectal adenocarcinomas

BACKGROUND: In order to elucidate the significance of myofibroblasts in invasive growth of colorectal adenocarcinomas, we examined the number of myofibroblasts at the tumor border of colorectal adenocarcinomas. METHOD: A total of 91 invasive colorectal adenocarcinomas were examined immunohistochemically using anti-alpha-smooth muscle actin (ASMA) and high-molecular-weight caldesmon (h-CD) antibodies; 25 carcinomas confined to the submucosa (sm carcinomas), 40 carcinomas confined to the muscularis propria (mp carcinomas) and 26 carcinomas invading the subserosa or adventitia (ss carcinomas). We considered ASMA-positive and h-CD-negative stromal cells as myofibroblasts. RESULTS: Twenty-seven (67%) of the 40 mp carcinomas and 25 (96%) of the 26 ss carcinomas had a small number of myofibroblasts at the tumor border facing the muscularis propria. CONCLUSIONS: Although direct evidence is lacking, there is a possibility that the further immediately vertical and radial invasion of carcinoma cells into the subserosa or adventitia is associated with a smaller number of myofibroblasts at the tumor border facing the muscularis propria in mp carcinomas, resulting in a low incidence of mp and a high incidence of ss carcinomas in the colorectum.      

Present diagnostic status of scirrhous type gastric cancer--with special reference to the endoscopic diagnosis

First, we presented an actual diagnostic situation in nowadays for gastric cancer of Borrmann 4, which is virtually the same as scirrhous gastric cancer. Among 12 patients treated by the author, all of whom were discovered late, only 3 underwent surgery. In fact, with inoperable cases in Borrmann 4, even those endoscopically found to show insufficient stretching of the gastric wall, thickening and tortuosity of folds, uneven gastric mucosa, redness and white coating, there may be negative in gastric biopsy. However, the significance of an endoscopic examination for diagnosis of scirrhous cancer is in obtaining proof of the carcinoma (especially when still operable) by gastric biopsy. Thus, one must strive not to overlook slight redness, white coating which means small erosions, but to go over gastric biopsy again and again. Next, with carcinoma presenting a leather bottle (linitis plastica type) of the stomach itself, the II c portion of the stomach consisted of fundic glands (undifferentiated carcinoma) shall become the primary focus supporting Nakamura's theory. One case of diffuse invasive cancer, mistakenly diagnosed as a II c case, and two cases of regional type, one similar to II c and the other a Borrmann 2 carcinoma of advanced carcinoma showing strongly fibrous scirrhous tendency toward infiltration, were jointly monitored.     

Early gastric carcinoma with special reference to macroscopic classification

During a period beginning in 1946 and ending in October of 1978, 1000 cases of solitary early gastric carcinoma were operated on at the Cancer Institute Hospital, Tokyo, Japan. The clinical characteristics and the macroscopic and chronological changes were studied in these cases. Early gastric carcinoma comprised one third of all resected gastric carcinoma. If early gastric carcinoma was divided into two groups, the depressed and the elevated, the former was more common. By location, the depressed type lesions were more frequently seen in the middle third of the stomach and the elevated type lesions in the lower third. By age, distribution of the elevated type lesions showed a peak with a mode at the age of 60 to 69 years and of the depressed type, a plateau with a mode at the age of 50 to 59 years. The relative incidence of the elevated type of gastric carcinoma to the depressed type was one to four. In depth of invasion, the mucosa and the submucosa were equally involved. Lymph node metastases were encountered in 12.7% of early gastric carcinoma cases. The incidence of positive nodes in mucosal carcinoma was 3.4% and that of submucosal lesions was 21.7%. Of the elevated type carcinoma, 20.9% of the cases had positive nodes. The 5-year survival rate of the patients with surgery for cure was 93.8% in contrast to 56.5% of those with palliative resection.     

Width of serosal invasion and prognosis in advanced human gastric cancer with special reference to the mode of tumor invasion

We studied the influence of the width of serosal invasion on the prognosis, in relation to the mode of invasion, in 142 patients who had curative resection for gastric carcinoma that invaded beyond the muscularis propria. The mode of invasion was classified into infiltrative and expanding types. Average diameter of tumor at the serosal or subserosal layer for the infiltrative type was 4.2 +/- 3.2 cm, a value significantly greater than that of 2.5 +/- 2.0 cm for the expanding type (P less than 0.01). The 5-year survival rate of patients with the infiltrative type carcinoma was significantly lower (36.8%) than that with the expanding type carcinoma (50.0%) (P less than 0.05). In the infiltrative type, the survival time of patients with a serosal invasion exceeding 2 cm was significantly shorter than when the serosal invasion was less than 2 cm (P less than 0.05). In the expanding type, however, the prognosis was good until the width of serosal invasion extended to 4 cm or greater. The difference in survival according to the width of serosal invasion did not always depend on the incidence of positive lymph nodes in both types of carcinomas. Therefore, influence of the width of serosal invasion on the prognosis for advanced gastric carcinomas differs between infiltrative and expanding types.     

Minute gastric carcinoma of differentiated type with special reference to the significance of intestinal metaplasia, proliferative zone, and p53 protein during tumor development

BACKGROUND: The differentiated type of minute gastric carcinoma (MGC), measuring less than 5 mm in greatest dimension, has been considered to represent the incipient phase of gastric carcinoma. To determine the clinicopathologic features of MGCs, the authors examined tissues from MGCs with a view to clarifying their histopathologic diversity. The immunohistochemistry of these tissues was determined using monoclonal antibody against p53 and Ki-67, and their mucin-histochemical types were determined with reference to the presence of intestinal metaplasia (IM) within their surrounding mucosa. METHODS: One hundred three specimens were obtained from 93 patients with MGCs. Each lesion was evaluated both macroscopically and histologically, and the degree of IM was assessed. All sections were examined mucin-histochemically with Con A, GOS, and HID-AB, and stained with commercially available monoclonal antibodies, PAb 1801 and Ki-67. Additional nonminute carcinomas present within the same stomachs were used as controls. RESULTS: Macroscopically, most lesions were depressed. IM was noted in the surrounding mucosa of 85 MGCs (82.5%). Immunohistochemically, 25 MGCs (24.2%) showed p53 overexpression, although the rate of p53 overexpression was increased to 34.6% in other nonminute carcinomas from the same stomachs. Twenty-four MGCs were associated with a proliferative zone, demonstrated by Ki-67 positive cells. Statistically significant differences in the rate of p53 overexpression were observed between MGCs with a proliferative zone and those without. Mucin phenotypes of MGCs tended to imitate their own surrounding mucosa. CONCLUSIONS: The MGCs, which represent the incipient phase of early gastric carcinoma, have various histologic, immunohistochemical, and mucin-histochemical features. It would seem that p53 expression is more closely related to the progression of MGCs than to their carcinogenesis.     

Multiple gastric cancers in the aged with special reference to intramucosal cancers

A histopathologic study was made on 512 specimens of gastric cancer that were surgically obtained from aged patients (mean age 73 years) in the Tokyo Metropolitan Geriatric Hospital. Of the 512 cases studied, 408 were gastric cancer of the glandular type (80%) and 104 were of the nonglandular type (20%). There were 75 cases of gastric cancer consisting of multiple independent cancer lesions and 71 of these were histologically diagnosed as multiple (2-5) gastric cancers composed of glandular type only. Of these 71 cases, 21 cases were multiple intramucosal cancers. These 21 cases of multiple intramucosal cancers were compared with 49 cases of single intramucosal cancers of glandular type in terms of the maximum diameter of each lesion and the location within the stomach. The results suggest that, in aged patients, there is a great possibility that collision of multiple cancer lesions may result in a single intramucosal gastric cancer measuring over 3 cm in diameter.     

Differential surface structures of invasive and non-invasive Ehrlich ascites tumor cell lines with special reference to the effect of hydrocortisone treatment.

The purpose of this study is to investigate the relation between the fine structure of the tumor cell surface and the tumor malignancy by scanning electron microscopy. Practically, comparison was made between the invasive Ehrlich ascites clone 1 tumor and the non-invasive Ehrlich ascites clone 3 tumor, and also between the 4th postinoculation day and the 6th postinoculation day as regards the growth of microvilli on the cell surface. On the 4th postinoculation day, an invasive clone 1 tumor cell was indistinguishable from a non-invasive clone tumor cell because of their common paucity of microvilli development. On the 6th postinoculation day, the former was associated with exuberant growth of microvilli, and was clearly distinguished from the latter in which the density of microvilli stayed low as before. The appearance of dense microvilli growth in the invasive clone 1 tumor cells chronologically coincided with the stage of fatal bleeding into the abdominal cavity. Hydrocortisone with a dose of 1 mg/mouse, when given subcutaneously to a tumor-bearing mouse on the 4th postinoculation day, stimulated the development of microvilli in both clone 1 and clone 3 tumors. The enhancing effect of the hormone on this process was detectable 2 hours after hormone injection. It was indicated that the dense growth of microvilli in the clone 1 tumor facilitated its tumor invasion into visceral organs, and that the enhancing effect of hydrocortisone on microvilli development was to be related to the promotion of malignant transformation. The possible implications of glucocorticoid in mammocarcinogenesis are discussed from the point of view of comparative endocrinology.     

A histopathological study of gastric cancer with liver metastasis, with special reference to poorly differentiated adenocarcinoma of the medullary type

Thirty-nine gastric cancer patients with liver metastasis on laparotomy were histologically analyzed. Poorly differentiated adenocarcinoma of the medullary type was the most common histologic type followed by papillary adenocarcinoma. Analysis of 32 gastric cancer patients who manifested liver metastasis after the operation showed that papillary adenocarcinoma and poorly differentiated adenocarcinoma of the medullary type were frequent. We conclude that poorly differentiated adenocarcinoma of the medullary type is the most common histologic type of gastric carcinoma metastasizing to the liver.     

Correlation of numerical and structural status of chromosome 16 with histological type and grade of non-invasive and invasive breast carcinomas.

Loss of heterozygosity on chromosome arm 16q frequently occurs in human breast carcinomas regardless of the histological grade or type. To reveal whether the status of chromosome 16 corresponds to the histology of breast carcinomas, we examined the signal number of 16cen, 16q breakpoints and 1;16 fusions in the interphase nuclei of 185 breast carcinomas using fluorescence in situ hybridization to detect the loci D16Z2 (16cen), D16Z3 (16q11), D16S154 (16q24) and D1Z1 (1q12). A 16q loss associated with a proximal or distal breakage was identified as a discrepancy between the modal signal counts of the D16Z2, D16Z3 and D16S154 loci in each tumor. Clonal 16cen aneusomy, proximal breakages, distal breakages and 1;16 fusion were detected in 62%, 35%, 34% and 38% of the carcinomas respectively. Each of these alterations correlated with the histology of both non-invasive and invasive carcinomas; 16cen aneusomy was more frequent in carcinomas of high histologic grade, proximal breakage was more frequent in invasive ductal carcinomas (IDCs) of the strand or solid types and in grade-2 and -3 carcinomas, and distal breakage was more frequent in tubular/cribriform type IDCs and grade-1 carcinomas. 1;16 fusion correlated with the tubular/cribriform type of non-invasive or invasive carcinomas and invasive lobular carcinomas. Proximal breakage correlated with 16cen aneusomy, whereas the distal breakage correlated with 16cen disomy. These structural and numerical chromosome alterations appeared to occur in association with each other, and their specific combinations appeared to be involved in the establishment of morphological variety among breast carcinomas. Int. J. Cancer (Pred. Oncol.) 84:381-387, 1999.     

Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

Background  Angiogenesis plays an important role in tumor growth and metastasis. Thymidine phosphorylase (TP), as well as vascular endothelial growth factor (VEGF), is known to be an angiogenic factor. The aim of this study was to clarify whether TP regulates angiogenesis and to determine the clinicopathological role of TP expression in gallbladder cancer. Methods  Thirty-seven patients with gallbladder cancer who underwent curative surgical resection were included in this study, and we evaluated results in 21 of these patients in whom TP gene expression could be measured. Intratumoral TP gene expression was evaluated using the Danenberg tumor profile method. TP gene expression was classified into two groups according to median values: high and low. Tissue TP expression was classified into two groups (positive and negative) by a pathologist. Clinicopathological variables were compared between groups with high and low TP gene expression (TP high and TP low groups). Results  No correlation was observed between TP gene expression (high and low groups) and any clinicopathological variables except survival rate. However, the survival rate was significantly lower in the TP high group (P < 0.05). TP gene expression was associated with tissue TP expression evaluated by immunohistochemical staining (P < 0.05). In addition, tumor microvessel density was significantly higher in the TP high group (P < 0.05). Conclusion  Expression of the TP gene in gallbladder carcinoma is associated with angiogenesis and may be a new independent prognostic parameter.