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Jpn J Clin Oncol

Elevated serum interleukin-6 levels in patients with pancreatic cancer.

Year 1998
Okada S. Okusaka T. Ishii H. Kyogoku A. Yoshimori M. Kajimura N. Yamaguchi K. Kakizoe T.
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis and they eventually become so emaciated that death primarily occurs from cancer cachexia. Cancer cachexia may be mediated by certain cytokines such as interleukin-6. In this study, we measured serum interleukin-6 levels in 55 patients with histologically proven pancreatic cancer and investigated their relationships to the clinical status of pancreatic cancer. A control population of 20 normal healthy adults and 25 chronic pancreatitis patients with comparable gender and age distribution characteristics was also studied. Serum interleukin-6 levels were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Thirty pancreatic cancer patients (54.5%) had detectable levels, although interleukin-6 levels were detectable in only one healthy control and in two chronic pancreatitis patients. The specificity of serum interleukin-6 in this population was 93.3%, resulting in high diagnostic accuracy (72.0%). Among the pancreatic cancer patients, the detection rates of serum interleukin-6 levels increased significantly with the disease extent (p < 0.01). Moreover, a significant difference was also found in the detection rates between the 30 pancreatic cancer patients with body weight loss (76.7%) and the remaining 25 patients without weight loss (28.0%, p < 0.01). These results may provide new insight into both diagnosis and treatment of pancreatic cancer, because the diagnostic accuracy of serum interleukin-6 was high and because anti-interleukin-6 therapeutics could improve symptoms in pancreatic cancer patients with high interleukin-6 levels.

Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced colorectal cancer: Taiwan experience.

Year 1998
Wang WS. Chen PM. Chiou TJ. Liu JH. Lin JK. Lin TC. Chen WS. Jiang JK. Yen CC. Fan FS. Hsieh RK.
Department of Medicine, Veterans General Hospital-Taipei, Taiwan.
Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.

Cancer incidence in Japan, 1985-89: re-estimation based on data from eight population-based cancer registries. The Research Group for Population-based Cancer Registration in Japan.

Year 1998

No information.
The Research Group for Population-based Cancer Registration in Japan has been conducting a cooperative study to estimate cancer incidence in Japan since 1975. Estimated incidence data calculated annually were accumulated in 1996 for 18 years. The Group has separately provided another re-calculated incidence estimate series which were prepared for 1975-79, 1980-84 and 1985-89. The former two results, each of five years were previously published elsewhere. These recalculated estimate series made more reliable observations of time trends in incidence feasible by using the same eligible registries' data throughout each 5-year period. This report presents results of the latter 5 years between 1985 and 1989; age-specific, crude and age-standardized incidence rates, as well as the number of incidence according to site and gender, under the cooperation of eight eligible population-based cancer registries in Japan: Miyagi, Yamagata, Kanagawa, Fukui, Osaka, Tottori, Hiroshima City and Nagasaki City. Incidence in Japan was estimated at 187,200 and 150,700 for all cancer sites among males and among females, respectively, in 1985 and 216,700 and 166,900, respectively, in 1989. The leading site was the stomach among both males and females from 1985 to 1989. Among males the second leading site was the lung, followed by the liver, colon and rectum. Among females, it was the breast, followed by the colon, uterus and lung in 1989. The proportion of the cases registered by a death certificate only for all sites was 14.0-15.7 and 13.7-15.3% and the ratio of incidence to mortality was 1.69-1.73 and 1.95-2.01 among males and females, respectively, during the period.

CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues.

Year 1998
Matsuda S. Yamane T. Hamaji M.
Institute of Clinical Research, Kure National Hospital, Hiroshima, Japan.
Intraepithelial T lymphocytes have been reported as being functional in the growth of epithelial cells and also in the discrimination of aberrant cells, whereas their function against colon adenocarcinoma cells is obscure. The phenotype of colon intraepithelial T lymphocytes has been found in patients with inflammatory bowel diseases but not in patients with colon adenocarcinoma. In this study, we investigated cell surface markers of tumor-infiltrating T lymphocytes of adenocarcinoma of the colon and rectum at various grades of differentiation and intraepithelial T lymphocytes of adjacent normal colon by enzyme immunostaining. Among intraepithelial T lymphocytes of the normal colon, CD8-and TCRgammadelta-positive T lymphocytes were predominant as described. In contrast, tumor-infiltrating T lymphocytes of well-moderately differentiated adenocarcinoma of the colon and rectum were predominantly CD4- and TCRalphabeta-positive. The decrease of TCRgammadelta-positive T lymphocytes and the increase of CD4 and TCRalphabeta-positive T lymphocytes in adenocarcinoma tissues of the colon and rectum suggests that an alteration of the local immune system participates in the formation of adenoma and/or adenocarcinoma of the colon and rectum, resulting in infiltration of CD4-positive T lymphocytes that have certain activity against transformed cells.

Usefulness of magnetic resonance imaging with dynamic contrast enhancement and fat suppression in detecting a pancreatic tumor.

Year 1998
Murakami K. Nawano S. Moriyama N. Onuma Y.
Department of Radiology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
The purpose of this study was to compare the value of dynamic magnetic resonance imaging (MRI) and fat suppression in detecting a pancreatic tumor. The subjects were 19 patients with invasive ductal adenocarcinoma and six patients with islet cell tumor where diagnosis was established pathologically. Breath-hold gradient echo images, breath-hold gradient echo images with fat suppression and breath-hold gradient echo images with dynamic enhancement at 1.5 T were obtained for all patients. The efficacies of these three imaging techniques were compared by calculating the contrast-to-noise ratio, as indicative of conspicuousness between a tumor-affected and a normal pancreas. As for adenocarcinoma, our results indicated that the usefulness in detecting the tumor was high, decreasing in the order dynamic contrast images > fat suppression images > plain images, and that the difference between any two of these three types of image was statistically significant. On the other hand, these imaging techniques showed no statistically significant difference in detecting islet cell tumors. In conclusion, dynamic MRI is the best method for detecting pancreatic adenocarcinoma. As the fat suppression technique has the advantage of being non-invasive, this method is suitable for screening studies of pancreatic adenocarcinoma. However, no advantage was recognized in using the fat suppression technique for detecting an islet cell tumor in comparison with plain MRI.

The outcome of surgical treatment for gastric carcinoma in the elderly.

Year 1998
Katai H. Sasako M. Sano T. Maruyama K.
Department of Surgical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Surgeons are increasingly being faced with the problem of treating elderly gastric carcinoma patients. The purpose of this study was to elucidate the feasibility of surgical treatment for these patients. Among 4740 gastric carcinoma patients treated from 1971 to 1990, 112 (2.4%) were aged 80 or over. The results of treatment in this elderly group were compared retrospectively with those in 2664 younger gastric carcinoma patients (aged 50-69, control group, 56.2%). The TNM stage distribution and the curative resection rates (75.9 vs 81.4%) were similar between the groups. Reduced nodal dissection was more common in the elderly group. The elderly had a higher incidence of preoperative risk factors (76.8 vs 53.1%) and 90-day mortality (10.7 vs 3.9%). However, the postoperative complication rates were similar between the groups. The 90-day mortality rates in the elderly group were higher in the subgroups undergoing total gastrectomy or D2 dissection. In the patients without pre-existing morbidity, the 30-day mortality, 90-day mortality and postoperative complications were similar between the groups. The 5-year survival rate after curative resection of the elderly group was significantly lower than that of the control group (44.4 vs 74.0%). This difference lost significance when non-cancer death was excluded (62.5 vs 79.9%). We believe that, although gastrectomy can be carried out safely in elderly patients, extended surgery should be limited to those without preoperative morbidity.

Complications after surgery for gastric cancer in patients aged 80 years and over.

Year 1998
Roviello F. Marrelli D. De Stefano A. Messano A. Pinto E. Carli A.
Istituto Policattedra di Scienze Chirurgiche, Second Department of Surgery, University of Siena, Italy.
Recent studies have shown a considerable increase in the number of aged patients with gastric cancer. In this retrospective study, we report our 18-year experience with 110 patients aged 80 years and over affected with this neoplasm. Postoperative morbidity and mortality rates and risk factors affecting their incidence were examined by univariate and multivariate analysis. Operability and resectability rates were 70.9% and 47.3% respectively. Of the resective procedures, 41 (78.8%) were subtotal gastrectomies. In five cases (9.6%), we performed combined resections. Twenty-five patients (32.1%) experienced postoperative complications; overall mortality rate was 12.8% (10 patients). In resective procedures, morbidity and mortality were 26.9% and 3.8% respectively, which are very low rates compared to other Western reports. Statistical analysis identified the number of preexisting medical illnesses as an independent predictor of morbidity and mortality. Crude five-year survival rate of curatively resected cases was 43%. Although multiple medical illnesses involved much higher operative mortality, neither the presence of postoperative complications nor the number of preexisting medical illnesses significantly influenced five-year survival rate of curatively resected patients. With careful evaluation and selection of patients, correct treatment of concomitant diseases and adequate peri- and postoperative care, gastric surgery provides good immediate and long-term results even in very old patients. Subtotal gastrectomy with limited lymphadenectomy should be the preferred procedure; total gastrectomy, combined resections and extended lymphadenectomy should be performed only when necessary, in patients with fewer than two illnesses. Surgery should be avoided in patients with highly advanced disease, if multiple medical illnesses are present.

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer.

Year 1998
Inomata M. Ochiai A. Sugihara K. Moriya Y. Yamaguchi N. Adachi Y. Kitano S. Hirohashi S.
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.

Navoban (tropisetron, ICS 205-930) and dexamethasone combination in the prevention of vomiting for patients receiving preconditioning high-dose chemotherapy before marrow transplantation.

Year 1998
Yen CC. Hsieh RK. Chiou TJ. Liu JH. Fang FS. Wang WS. Tung SL. Tzeng CH. Chen PM.
Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taiwan.
The anti-emetic efficacy of a combination of tropisetron and dexamethasone was studied in 33 patients who underwent bone marrow transplantation. Another 50 patients receiving conventional anti-emetic therapies in bone marrow transplantation served as control. On the first and second days of preconditioning chemotherapy, 51% and 36% respectively of patients in the tropisetron and dexamethasone group did not experience vomiting, compared with only 12% and 10% of control group patients (P < 0.001). The mean number of episodes of vomiting in the tropisetron and dexamethasone group was also significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in the two groups was not significantly different during days 3-6. Analysis of patients receiving busulfan and cyclophosphamide as the preconditioning regimen still showed better anti-emetic control in the tropisetron and dexamethasone group than in the control group on the first two days of treatment (total control rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given tropisetron and dexamethasone combination more frequently suffered from dizziness and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms were the most frequent adverse effects seen after using conventional anti-emetic combination. The combination of tropisetron and dexamethasone was thus superior to conventional anti-emetic combinations in preventing vomiting during preconditioning period of bone marrow transplantation. The adverse effects of this combination were minimal and well tolerated by patients.

A case of malignant peritoneal mesothelioma showed complete remission with chemotherapy.

Year 1998
Ito H. Imada T. Kondo J. Amano T. Maehara T. Rino Y. Takahashi M. Shiozawa M. Hatori S. Suzuki Y.
First Department of Surgery, Yokohama City University, School of Medicine, Kanagawa, Japan.
A 71-year-old woman presented with an abdominal mass and ascites and was subsequently admitted to our hospital in June 1995. Further examination revealed that the mass was malignant and, as a result, surgery was indicated. However, the mass demonstrated widespread peritoneal dissemination, which therefore could not be resected, and pathological findings suggested a malignant peritoneal mesothelioma. The patient showed a remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur (UFT) in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to the CT. Hence chemotherapy was judged to have resulted in complete remission. Such a marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma such as the present case. Eight months later, the tumor recurred in the pleura. Another regimen of chemotherapy with cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure in January 1997 due to the mesothelioma. This is a case report of complete remission of malignant peritoneal mesothelioma by combined chemotherapy.

Anastomotic recurrence after curative resection of a transverse colon carcinoma: a case report.

Year 1998
Miyake H. Moriya Y. Maruyama K. Yokota T. Shimoda T.
Department of Surgery, National Cancer Center Hospital, Tokyo, Japan.
We report a case of anastomotic recurrence after curative surgery for transverse colon cancer in a 53-year-old man. The recurrence was first detected as a submucosal tumor 1.3 cm in diameter, located on the suture line, during an annual follow-up barium enema and colonoscopy. A repeat examination 3 months later showed the lesion to be a typical colon cancer, 2.5 cm in size, with a large ulcerated area. Right hemicolectomy was performed with curative intent. Anastomotic recurrence is much rarer after colonic resection than after anterior resection. This was the first time that we had detected a recurrent lesion as a submucosal tumor during annual follow-up examination.

Experimental chemical carcinogenesis in the stomach and colon.

Year 1998
Sugimura T. Terada M.
National Cancer Center, Tokyo, Japan.
Experimental chemical carcinogenesis in the digestive tract is reviewed, mainly on the basis of information obtained in the laboratories of the National Cancer Center Research Institute. It is generally accepted that cancer is the outcome of DNA damage, resulting in mutation, loss, amplification and recombination of genes. Gastric cancer is no exception. It was shown very early that cancer of the glandular stomach can be produced in rats by administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a widely used mutagen. However, this depends on the genotype. Whereas the ACI rat is susceptible to MNNG, the Buffalo rat is resistant and this is a dominantly inherited trait. Genes responsible for the sensitivity to gastric cancer induction are at present under investigation by linkage analysis of rat genome markers. With regard to cancer in humans, our finding that cooked proteinaceous foods can give rise to a series of heterocyclic amines (HCAs) is of major significance. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most abundant, causes colon cancers in male rats, whereas in females it induces breast cancers. The colon cancers induced by PhIP feature a deletion of G as represented by 5-GGGA-3-->5-GGA-3 in the Apc gene, resulting in a truncated Apc molecule. Microsatellite mutations have also been found in PhIP-induced colon tumors, as in human hereditary non-polyposis colorectal cancer cases. Similarly to the case of gastric cancer production by MNNG, there is a genetic component and F344 rats are more susceptible to PhIP colon carcinogenesis than the ACI/N strain and the gene responsible is being sought. Since carcinogenesis proceeds with accumulation of genetic alteration, often involving genomic instability, exposure to any kind of carcinogenic substances, either xeno- or autobiotics, needs to be reduced as far as possible, taking account of inconvenience at the individual and socio-economical levels.

Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration.

Year 1998
Ikeda K. Terashima M. Kawamura H. Takiyama I. Koeda K. Takagane A. Sato N. Ishida K. Iwaya T. Maesawa C. Yoshinari H. Saito K.
Department of Surgery 1, Iwate Medical University, Morioka, Japan.
BACKGROUND: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. METHODS: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2, days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (Cmax) of total and free Pt were investigated. RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01 microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.

Frequent expression of the vascular endothelial growth factor in human non-small-cell lung cancers.

Year 1998
Takahama M. Tsutsumi M. Tsujiuchi T. Kido A. Okajima E. Nezu K. Tojo T. Kushibe K. Kitamura S. Konishi Y.
Department of Oncological Pathology, Nara Medical University, Japan.
BACKGROUND: Angiogenesis is an essential factor for progression and metastases in solid tumors. It has been reported that several angiogenic factors play a role in the regulation of angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important molecules in angiogenesis. We investigated expressions of VEGF in a series of lung carcinomas with regard to clinicopathological factors. METHOD: VEGF expression was investigated by use of immunohistochemical studies and Northern blot analysis, using 155 primary and 26 metastatic lung carcinomas for the immunohistochemical studies and 10 primary and two metastatic lung carcinomas for the Northern blot analysis. All lesions were resected at surgery. RESULTS: The frequencies for positive VEGF expression were 64 of 74 (86.5%) adenocarcinomas, 38 of 67 (56.7%) squamous cell carcinomas, four of four (100%) large cell carcinomas, two of three (66.7%) adenosquamous carcinomas and one of five (20%) small-cell carcinomas, the degree of positivity generally being greater in well differentiated tumors. The majority of metastatic foci from adenocarcinomas and squamous cell carcinomas at other sites were also positive (76.5 and 66.7%, respectively). VEGF expression did not correlate with clinicopathological factors such as tumor size or pathological stage, but pathological stage I adenocarcinoma cases positive for VEGF demonstrated a shorter disease-free period when followed up for 48 months than those cases expressing VEGF negatively. CONCLUSIONS: The results indicated that VEGF expression was frequently detected in non-small-cell lung cancers and suggested that VEGF might relate to the disease-free period of the patients with early adenocarcinomas.

Identification and characterization of families with aggregation of lung cancer.

Year 1998
Tomizawa Y. Adachi J. Kohno T. Yamaguchi N. Saito R. Yokota J.
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
BACKGROUND: To clarify genetic factors involved in the susceptibility to lung cancer, it is essential to identify families with lung cancer clustering and to characterize the mode of clustering. Since somatic mutations of the p53, RB and p16 genes occur frequently in lung cancer and the replication error phenotype is seen in a subset of lung cancer, it is possible that germ-line mutations of the p53, RB, p16 and mismatch repair genes influence the susceptibility to lung cancer. METHODS: In this work, cases with familial clustering of lung cancer were selected from 1068 families with primary lung cancer cases in analogy with the criteria for hereditary non-polyposis colorectal cancer (HNPCC). Cases with Li-Fraumeni syndrome, familial retinoblastoma, familial melanoma and HNPCC were also searched among these 1068 families. RESULTS: There were only four families (0.4%) in which more than three relatives were affected by lung cancer. Two successive generations were affected in 36 families (3.4%). Patients with lung cancer before the age of 50 were present in 165 families (15.5%). However, no family conformed to all three criteria. There was only one family with Li-Fraumeni syndrome and no family with familial retinoblastoma, familial melanoma and HNPCC. CONCLUSION: Familial aggregation of lung cancer is rare and germ-line mutations of the p53, RB, p16 and mismatch repair genes may not contribute greatly to susceptibility to lung cancer.

Growth patterns and genetic changes of colorectal carcinoma.

Year 1998
Kaneko K. Fujii T. Kato S. Boku N. Oda Y. Koba I. Ohtsu A. Hosokawa K. Ono M. Shimoda T. Yoshida S.
Department of Medicine, National Cancer Center Hospital East, Chiba, Japan.
BACKGROUND: Recent Japanese studies have shown that histogenesis of small colorectal carcinomas can be divided into two groups: polypoid growth arising from polypoid neoplasia, and nonpolypoid growth arising from flat or depressed neoplasia. This classification should be verified with genetic as well as morphologic characteristics. SUBJECTS AND METHODS: In order to classify our subject into polypoid growth and nonpolypoid growth types both histologically and endoscopically, we selected 42 colorectal carcinomas < 2 cm in size (35 submucosal and seven more advanced). Clinicopathological findings, presence or absence of Ki-ras gene mutation and overexpression of p53 protein were compared between the two types. RESULTS: Histologically, the cases were divided into 27 of the polypoid growth type and 15 of the nonpolypoid growth type. None of the nonpolypoid growth cases contained adenomatous remnant, wheras this was found in 75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the nonpolypoid growth cases, although it appeared in 44% of the polypoid growth cases. Regarding the overexpression of p53 protein, no significant difference was observed between the two types. The histological and the colonoscopic polypoid growth-nonpolypoid growth classifications correlated well with each other (agreement rate 98%), except for one lesion, which was classified as polypoid growth type endoscopically but as nonpolypoid growth type histologically. CONCLUSIONS: The histologically defined polypoid growth-nonpolypoid growth classification may indicate a difference in pathway of colorectal carcinogenesis. Also, colonoscopic polypoid growth-nonpolypoid growth classification is available for preoperative estimation of the genetic characteristics of small carcinomas.

Characteristics in primary signet-ring cell carcinoma of the colorectum, from clinicopathological observations.

Year 1998
Sasaki S. Masaki T. Umetani N. Futakawa N. Ando H. Muto T.
First Department of Surgery, University of Tokyo, Japan. SASAKI-ISU@h.u-tokyo.ac.jp
BACKGROUND: The biological behavior of signet-ring cell carcinomas in colorectum tends to be worse than that of mucinous carcinomas. However, in previous studies, clinicopathological features of this disease have been somewhat ill-defined because various histological criteria of this disease were adopted. METHODS: We selected 11 cases of signet-ring cell carcinomas and 29 cases of mucinous carcinomas among 1595 consecutive colorectal carcinomas on defined criteria and compared clinicopathological and molecular biological features between these two types of carcinomas. RESULTS: Clinical staging of signet-ring cell carcinomas were far advanced and their prognosis tended to be worse than that of mucinous carcinomas. Furthermore, the incidence of K-ras mutations in signet-ring cell and mucinous carcinomas showed no difference between these two types of carcinomas. However, the incidence of K-ras mutation in these diseases was slightly lower than that in 30 ordinary colorectal carcinomas examined as a comparison. CONCLUSIONS: These results suggest that the carcinogenesis of signet-ring cell and mucinous carcinomas are different from that of ordinary colorectal carcinomas and that there may exist other genes related to malignancy of signet-ring cell carcinomas.

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