Diagnosis of depressed‐type early gastric cancer using small‐caliber endoscopy with flexible spectral imaging color enhancement

Background and Aim: Small‐caliber endoscopy has lower resolution than normal‐caliber endoscopy, limiting its use in routine outpatient practice. Flexible spectral imaging color enhancement (FICE) strengthens the color contrast of depressed‐type early gastric cancer without magnification. The aim of the present study was to evaluate the detection of depressed‐type early gastric cancer using small‐caliber endoscopy with the FICE system. Methods: Eighty‐two patients diagnosed with depressed‐type early gastric cancer by standard endoscopy and biopsy were evaluated by small‐caliber endoscopy. FICE images and conventional images were compared. Color differences in all 82 lesions were measured between malignant lesions and the surrounding mucosa using the Commission Internationale de L'Eclairage (CIE) 1976 color space. Results: Most cancers were readily detected as reddish lesions on FICE images. Lines of demarcation between the malignant lesion and the surrounding mucosa were easily identified with FICE images, as such cancers could be clearly distinguished from the surrounding atrophic mucosa. Greater median color differences between malignant lesions and the surrounding mucosa were present in FICE images compared with conventional images, resulting in images with better contrast (27.2 vs 18.7, P < 0.0001). Conclusions: Small‐caliber endoscopy with the FICE system provides better color contrast of depressed‐type early gastric cancers than conventional small‐caliber endoscopy, and the FICE system may facilitate the diagnosis of this type of cancer as a new endoscopic modality.     

Present Status of Early Colorectal Cancer in Japan

We examined and clinicopathologically analyzed 422 patients with early colorectal cancer that we encountered, and discussed the problems typical of early colorectal cancers in Japan. In Japan we define early colorectal cancer as consisting of intramucosal cancer and cancer with submucosal invasion. Because histopathologists subjectively diagnose patients with intramucosal cancer, their diagnoses for the same specimen often differ from each other. The only way to avoid such confusion caused by diagnostic differences and to reach a consensus on the diagnosis of intramucosal cancer is to make a diagnosis of intramucosal cancer only in those patients who clearly show the structural atypia and/or the cellular atypia, that are typical of cancer. No one will deny the importance of the depressed type early cancer, the number of cases of which have recently been increasing in Japan. However, it is also important to assert that endoscopically-discovered depressed neoplastic lesions are not always cancer. In the depressed neoplastic lesions discovered in our patients, the number of adenoma was almost three times that of cancer. Forty percent of the patients with depressed type early cancer also had an adenoma component. Therefore, at this moment we cannot conclude that early cancer with a depression is de-novo-genetic colorectal cancer. Eighty percent of early colorectal cancers are discovered to be the protruded type of early cancer. Twenty-six percent of early cancers with submucosal invasion, including early cancers with massively submucosal invasion, are 6 to 10 mm in diameter and 76% of these are protruded early cancers. These facts indicate that colorectal tumors, protruded or depressed, which are more than 6 to 10 mm in diameter should be endoscopically removed to prevent them from becoming advanced cancers.     

Clinicopathologic Characteristics of Interval Gastric Cancer in Korea

Background/AimsInterval gastric cancer (IGC) is defined as cancer that is diagnosed between the time of screening and postscreening esophagogastroduodenoscopy (EGD). Unfortunately, little is known about the characteristics of IGC in Korea, a country with a high incidence of gastric cancer. The aim of this study was to evaluate the clinicopathologic characteristics of IGCs in Korea.MethodsFrom January 2006 to July 2011, a total of 81,762 subjects underwent screening EGD at Yonsei University Health Promotion Center, Seoul, Korea. We defined missed cancer as cancer diagnosed within 1 year of screening EGD and latent cancer as cancer diagnosed more than 1 year after EGD.ResultsA total of 16 IGC patients (17 lesions; three missed cancers and 14 latent cancers) were identified, with a mean age of 60.68 years and a mean interval time of 19.64 months. IGCs tended to be undifferentiated (12/17, 70.6%), located in the lower body of the stomach (12/17, 70.6%) and exhibited flat/depressed endoscopic morphology (11/17, 64.7%). The patients with missed cancer were generally younger than the patients with latent cancer (51.3 years vs 62.8 years, p=0.037), and the patients with undifferentiated cancer were significantly younger than those with differentiated cancer (57.0 years vs 68.8 years, p=0.008).ConclusionsIGCs tended to be undifferentiated, located in the lower body of the stomach, and exhibited flat/depressed endoscopic morphology.     

Clinicopathological and Endoscopic Studies on Gastric Cancer Located; the Cardia

Abstract: In this study the definition of cardiac cancer (histologically adenocarcinoma) was taken to be a cancerous lesion, the size of which is less than 4 cm and the center of which is located within 2 cm from the esophagocardiac junction. 42 patients (0.8%) fit the above definition of cardiac cancer out of 4,958 patients with solitary gastric cancer operated on at the National Cancer Center Hospital daring the period between 1962 and 1988. The clinicopathological and endoscopic findings of these 42 patients were compared with those of 132 patients with gastric cancer located in the upper third of the stomach other than in the cardia (cancer in the other C-area). In the group with cardiac cancer, the male patients (M/F ratio: 3.7), the elderly patients (mean age: 61.3 years), a differentiated type of adenocarcinoma (90%), lesions located at the lesser curvature (62%) and the elevated type of lesion were found to predominate. The incidence of early cancer (60%) and the incidence of small lesions less than 2 cm (32%) in diameter were lower than in the patients with cancers in the other C-area. In the group with cardiac cancer, however, the incidence of such types of early cancer as the depressed lesion, a small lesion less than 2 cm in diameter and lesions difficult to diagnose endoscopically, have been increasing. In recent years, cardicac cancers have been found not only on the lesser curvature, but also in different areas of the cardia. These results suggest an improvement in endoscopic diagnosis for cardiac cancer. To make early detection more precise, it will be indispensable not to overlook even faint or indistinct mucosal abnormalities at the area adjacent to the esophagocardiac junction.     

Characteristics of early colorectal carcinoma with lymph node metastatic disease

BACKGROUND/AIMS: Endoscopic resection may safely and effectively remove early colorectal cancers. However, additional surgical treatment is needed in cases with metastatic lymph nodes for curative treatment. The purpose of this study was to investigate the correlation between lymph node metastasis and various pathological parameters in early colorectal cancers. METHODOLOGY: The clinicopathological records of 3,557 colorectal adenocarcinoma patients who underwent surgical resection at the Samsung Medical Center from August 1995 to June 2005 were reviewed. One hundred forty seven tissue samples with early colorectal cancer were used in this study. Various parameters were studied including gender, location, macroscopic appearance, differentiation, lymphatic tumor emboli, and the depth of tumor invasion. RESULTS: Twenty five patients (17.0%) had lymph node metastasis. Male gender, left colon, macroscopically depressed lesions, moderately or poorly differentiated carcinoma, depth of tumor invasion (Sm2 or Sm3), and presence of lymphatic tumor emboli were the risk factors for lymph node metastasis. CONCLUSIONS: Early colorectal cancers with male gender, location in the left colon, macroscopically depressed lesion, moderate or poor differentiation, depth in Sm2 or Sm3, and the presence of lymphatic tumor emboli have higher risk of lymph node metastasis than those without. The early colorectal cancers with these risk factors should have surgical resection.     

Incidence of cancer in a cohort of patients with primary Sjogren's syndrome

OBJECTIVE: To compare the incidence of subsequent cancers in a cohort of patients with primary Sj?gren's syndrome (pSS) with that of the general population in the same region of England. METHODS: A retrospective analysis was carried out on 112 patients who had attended the out-patients department at University College Hospital, London, from 1979 onwards. Patients were followed up from diagnosis of pSS to diagnosis of first subsequent cancer, death, loss to follow-up or 31 December 2003 (the censoring date) to determine the person-years at risk for each individual. The expected numbers of subsequent cancers were calculated from sex-/age-/period-specific rates for the general population of southeast England, derived from registrations at the Thames Cancer Registry. Standardized incidence ratios (SIRs) were then calculated as the ratio of observed to expected numbers of cancers, along with 95% confidence intervals (CIs). Separate analyses were performed for all malignant cancers combined, lymphomas and non-lymphoid cancers. RESULTS: Among the 112 patients with pSS, 25 developed cancer (either before or after development of pSS), with lymphoma occurring in 11 cases. Nine patients had two cancers. There was a significantly elevated incidence of lymphomas in pSS patients compared with the general population (SIR 37.5, 95% CI 20.7-67.6). For non-lymphoid cancer, the observed increase in incidence was small and not statistically significant (SIR 1.5, 95% CI 0.9-2.6). CONCLUSION: This study confirms that there is an increased incidence of lymphoma in patients with pSS. An increase in the incidence of other cancers was not proven but the observation that some patients developed more than one cancer raises the possibility that there may be a subgroup of patients who are at greater risk of developing cancer.     

Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features

Flat-type colorectal tumors have are being detected with increasing frequency. It has become clear that these flat lesions contain two subtypes; flat-elevated and depressed lesions. However, their clinicopathological features and roles in colorectal carcinogenesis remain obscure. We classified colorectal adenomas and submucosal invasive cancers into three types: polypoid, flat-elevated, and depressed types. A clinicopathological study of 2505 colorectal tumors (2407 adenomas, 98 submucosal invasive cancers) was then performed. Furthermore, 64 tumors (25 adenomas with high-grade dysplasia, 39 submucosal invasive cancers) from which DNA was extracted were examined for K-ras gene mutation. The percentages of each configuration in the resected materials were 62.0%, 36.4%, and 1.6% of the polypoid, flat-elevated, and depressed types, respectively. The rate of submucosal invasive cancer in the depressed type was always high regardless of size. In the polypoid and flat-elevated types, lesions of larger size showed higher rates of invasion. Analysis of submucosal invasive cancers revealed no adenomatous components in any of the depressed-type lesions; in the polypoid and flat-elevated types the frequencies of cancer with adenomatous components were 83.6% and 77.8%, respectively. The flat-elevated type was more frequently located (77.8%) in the proximal colon than the other types (polypoid type 16.4%, depressed type 25.0%). The incidence of K-ras gene mutation was 47.2%, 18.2%, and 0% in the polypoid, flat-elevated, and depressed types, respectively. These findings suggest that the flat-elevated and depressed types are similar in that they are both morphologically flat and have infrequent incidences of K-ras gene mutation, but these two lesions differ in their pathological features. Especially, depressed type lesions have a tendency to invade the submucosal layer even when they are small. Therefore one should always be aware of this type of lesion during colonoscopic examination.     

Low prevalence of incidentally discovered and early-stage esophageal cancers in a 30-year autopsy study

Autopsy studies provide information that may guide future patient management. This study analyzed autopsy findings in patients with esophageal cancers, with emphasis on the prevalence of incidentally diagnosed esophageal cancer, histologic subtypes, early-stage lesions, and any associated pathology. Autopsies detected 346 patients (306 men; 40 women) with esophageal carcinomas during a 30-year period, constituting an overall prevalence of 3.4%. Out of these patients, 30 (8.7%) were incidentally discovered at autopsy. Squamous cell cancers were found in 336 (97.1%) patients, small cell cancers in nine (2.7%), and adenocarcinomas in one (0.3%). Stage distributions were stage I in seven patients (2%), stage II in 49 (14%), stage III in 121 (35%), and stage IV in 169 (49%). Isolated dysplasia or carcinoma-in-situ were not found. Comparing with symptomatic patients, patients with incidental cancers were older, had higher frequency of small cell carcinomas, and lower T-stage. The prevalence of incidentally diagnosed esophageal carcinomas and early-stage carcinomas were low. Unusual histologic subtypes may be found.     

Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial

BACKGROUND: Interval colorectal cancer (CRC) occasionally is detected in patients who have recently undergone colonoscopy. Systematic evaluation of CRC detected after colonoscopy could identify ways to improve the quality and the outcome of colonoscopy. METHODS: This study examined cancer diagnoses in the course of the dietary Polyp Prevention Trial, a randomized study of a dietary intervention on recurrence of adenomatous polyps. An algorithm was developed to classify each cancer into one of 4 etiologies: (1) incomplete removal (cancer at the site of previous adenoma), (2) failed biopsy detection (cancer in an area of suspected neoplasia with negative biopsy specimens), (3) missed cancer (large, advanced stage cancer found at a short interval after colonoscopy), or (4) new cancer (small, early stage cancer after a longer time interval). RESULTS: Of 2079 patients, 13 had cancer detected over 5810 person years of observation (PYO) (2.2 cases/1000 PYO); 7/13 or 53.8% of patients had either a potentially "avoidable" cancer or one detectable at an earlier time interval because of incomplete removal (4/13) or missed cancer (3/13). CONCLUSIONS: Interval cancer occurs despite colonoscopy. Improved quality of colonoscopy may have reduced cancer prevalence or resulted in earlier cancer detection in over 50% of prevalent cancers in the dietary Polyp Prevention Trial.     

Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?

BACKGROUND: There is a difference in the location of colorectal mucosal lesions and invasive cancers. AIMS: To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. METHODS: The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. RESULTS: (a) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (b) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. CONCLUSION: There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.     

Predicting histologic findings from endoscopic appearance of early gastric cancer.

In 156 cases of depressed early gastric cancer in the antrum or corpus, the differences between differentiated and undifferentiated carcinoma were studied by comparing the histological diagnosis of the resected specimens and their endoscopic appearance. We reached the following conclusions: (a) Younger patients more often had undifferentiated carcinoma (mean age: 59.8 years) than differentiated carcinoma (mean age: 77.2 years). (b) One hundred and twenty-five of 156 cases were limited to the mucosa and 29 cases were limited to the submucosa. (c) Undifferentiated gastric cancers more often invaded beyond the mucosa even when the tumor was small than did differentiated tumors. (d) Many differentiated tumors showed a smooth depressed surface, erythema at the edge of the cancer, and tapering of the gastric rugae. (e) In undifferentiated lesions the depressed tumor surface had a varied appearance, with various sized granules and nodules, as well as fading of the mucosal color and fusion of the rugae. It is important at endoscopy to consider not only whether a lesion is benign or a malignant, but also to consider its histological type. In particular, it is vital to detect small, undifferentiated gastric cancers as early as possible.     

Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Epstein–Barr virus‐associated gastric cancer (EBV‐GC) accounts for approximately 8% of gastric cancers. However, little is known regarding intramucosal EBV‐GC. The present study aimed to evaluate endoscopic and clinicopathological characteristics of intramucosal EBV‐GC. Pathological data of 172 patients with 173 intramucosal gastric cancers who received gastrectomy with lymph node dissection were obtained for review. EBV‐encoded small RNA in situ hybridization (EBER‐ISH) was carried out using a tissue microarray block. Eight intramucosal early gastric cancers (4.6%) were EBER‐ISH positive in which no cases had any lymph node metastasis. Macroscopic types were either depressed or flat, dominant histology was mixed type of moderate and poorly differentiated adenocarcinoma. In detail, histological features of “lace pattern” or “lymphocyte infiltration into the stroma or cancer nests” were observed.     

Evaluation of lateral lymph node dissection with preoperative chemo-radiotherapy for the treatment of advanced middle to lower rectal cancers

Background and aims This study examined rectal cancers with lateral lymph node (LN) metastases and whether lateral lymph node dissection (LLD) with or without preoperative chemo-radiotherapy (XRT) benefits patients with rectal cancer.Patients and methods A total of 452 consecutive cases of curatively resected pT2, pT3, and pT4 middle to lower rectal cancers were retrospectively analyzed. Of these, 265 patients underwent curative LLD and 155 XRT. Data were evaluated with respect to the cumulative percentage of survival.Results Lateral LN metastases were identified in 7.7% of patients. Of the pT3/pT4 extraperitoneal cancer patients 13.5/18.8% had lateral LN metastases. In the treatment of middle rectal cancers and pT2 extraperitoneal cancers LLD either with or without XRT did not improve survival rate. For the treatment of pT3/pT4 extraperitoneal tumors prior to the introduction of total mesorectal excision (TME) in 1994 LLD plus XRT yielded significantly better survival and local control than conventional surgery without LLD or XRT, although LLD alone did not improve either survival or local recurrence rates. Since 1995 TME with or without subsequent LLD has yielded favorable results for the treatment of extraperitoneal tumors.Conclusion For the treatment of middle rectal cancers and pT2 extraperitoneal cancers LLD either with or without XRT does not improve survival rate. For pT3/pT4 extraperitoneal tumors, which are associated with a high incidence of lateral node metastasis, combining treatment modalities such as TME followed by LLD or XRT followed by TME may be considered.This work was partially supported by a grant-in-aid for scientific research from the Japanese Ministry of Education (no. 11671149)An invited commentary on this paper is available at     

Early gastric stump cancer following distal gastrectomy

Background—Gastric stump cancer(GSC) is usually diagnosed at an advanced stage, and consequently theprognosis is poor.
Aims—To investigate theclinicopathological characteristics of GSC at an early stage to assistin its identification, and thereby improve its prognosis.
Methods—Forty three patients withresected early GSC were compared with 156 patients with resectedprimary early cancer in the upper third of the stomach.
Results—Sixty five per cent (28/43)of the early GSC patients showed the elevated type endoscopically,although the frequency of the depressed type in GSC has tended toincrease in the past five years. This occurred in less than 26%(40/156) of the primary early cancers. Half of the early GSCs werelocated on the lesser curvature (47%), and revealed differentiatedadenocarcinoma (81%) histologically. The male:female ratio of earlyGSC cases was about 6:1, which was much higher than that in patientswith primary early cancer. The five year survival rates of patientswith early GSCs and early primary cancers were 84% and 95%,respectively. GSC had a favourable prognosis, if it was detected at anearly stage.
Conclusion—To detect early GSC, ourresults suggest that special attention should be given to elevated aswell as depressed lesions on the lesser curvature of the stomach,particularly in men, during endoscopic examinations.

Keywords:gastric stump cancer; early gastric cancer; prognosis; endoscopy

     

Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer?

To determine the tumor size that constitutes early pancreatic cancer, we reviewed and analyzed the English-language and Japanese literature (a total of 25 publications) on small pancreatic cancers less than 2 cm in diameter and/or stage 1 cancers. Reports on in situ carcinoma and intraductal carcinoma of the pancreas were also evaluated. The results were: (1) A total of 302 cases of small pancreatic cancer less than 2 cm in diameter reported at separate institutions were pooled from 15 reports. The rates for patients in stage I and those with no lymph node metastasis averaged 41.7% and 57.9%, respectively. The 5-year postoperative cumulative survival rate (5Y-PCR) was less than 50% in almost all these reports. Similar data were shown in the 7 collective reviews. (2) Another 33 cases of small pancreatic cancer of 1 cm or less in diameter were collected from three reports. The rates for stage I tumor and 5Y-PCR at one institution with two reports were 100% and 100% and the rates in the other report were 85% and 78%, respectively. (3) Twelve cases of in situ carcinoma and intraductal carcinoma of the pancreas were collected from four reports. All of the patients were stage I and were alive with no evidence of tumor recurrence for periods ranging from 6 to 78 months. Small pancreatic cancer less than 1 cm in diameter is better viewed as an early pancreatic cancer, and in situ carcinoma and intraductal carcinoma of the pancreas with minimal invasion to the pancreatic parenchyma may be defined as early pancreatic cancer, regardless of size.     

Malignancies occurring during therapy with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and other hematologic malignancies

Success of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has given patients hope for a long disease-free-survival. A longer survival raises the question of late effects, including development of another malignancy. Records of 1445 patients with CML/myeloproliferative neoplasm or other hematologic malignancies treated with TKIs were reviewed to investigate frequency and characteristics of second malignancies (other than acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndrome). The number of second cancers was compared with the number expected from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 107 months (range, 13-362 months) after CML/myeloproliferative neoplasm diagnosis, 66 patients (4.6%) developed 80 second cancers, including skin (31%), prostate (15%), melanoma (13%), digestive system (10%), kidney (4%), thyroid (4%), breast (3%), chronic lymphocytic leukemia (3%), hepatobiliary (3%), and other cancers (14%). Excluding nonmelanoma skin cancers, 55 second cancers were seen in 51 (3.5%) of all patients treated. The risk of second cancer was lower than expected (observed-to-expected ratio, 0.6; 95% confidence interval, 0.44-0.81). Second cancers occur in a small percentage of patients receiving therapy with TKIs for hematologic malignancies, mostly CML. No evidence at the moment suggests that exposure to TKIs increases the risk of developing second cancers.     

Multiple primary cancers in patients with gastric cancer

BACKGROUND/AIMS: Some gastric cancer patients have multiple primary cancers (MPC). We evaluate the current status of MPC with gastric cancer. METHODOLOGY: 2,109 gastric cancer patients treated between 1987 and 2002 were analyzed. RESULTS: There were 99 MPC with gastric cancer (4.7%). Second cancer (77.8%) was discovered within 5 years before and after the onset of gastric cancer. 34.3% of patients were discovered within 1 year (synchronous tumor). In the 77 male patients, prostate cancer was the most common occurrence (19.5%), followed by cancers of the colon (18.2%) and liver (14.3%). In the 22 female patients, colon cancer was the most common (31.9%) followed by breast and cervix cancers (22.7%). These cancers were the most common diseases in Taiwan in the same period. Gastric cancer patients with MPC had less stromal reaction and better survival than those without. Patients with metachronous secondary tumors had more peritoneal dissemination and worse survival than those with synchronous primary cancer. CONCLUSIONS: Gastric cancer patients may develop second cancer(s), which is often a current prevalent malignancy. Knowledge of time to development and mode of organ association may allow clinicians to detect potentially curable subsequent cancer(s).     

A pilot study on the usefulness of a new test for mass screening of colorectal cancer in Japan

A new screening test (Shamsuddin and Elsayed, 1988) based on the enzymatic detection of the disaccharide Β-D-Gal(1→ 3)-D-GalNAc in the rectal mucus of patients with colorectal (CR) cancer and precancerous conditions such as inflammatory bowel disease (IBD) and polyp (precancerous lesions) was evaluated in 85 Japanese patients. Following a 15-minute reaction, a sensitivity of 80.0% (8/10) for CR cancer and 72.2% (8/11) for precancerous lesions was obtained. The overall specificity for combined CR cancers and precancerous lesions was 62.2% (28/45). Correlation with abnormal mucin production in the tissues of CR cancer and precancerous lesions was studied by high-iron diamine-Alcian blue and/or periodic acid-Schiff-Alcian blue (pH= 1.0). The agreement of the results with this test was 77.8% (7/9) for CR cancers and 75.0% (6/8) for precancerous conditions. Because of the simplicity of this test, low cost, stability of the sample and reagents and accuracy for CR cancer and precancerous lesions, the test may have potential use for mass screening of cancer and high risk individuals, particularly CR cancer in Japan. This paper was presented at the 48th annual meeting of the Japanese Cancer Association, Nagoya, October 23 to 25, 1989.     

Incidence of apoptosis increases with age in colorectal cancer

The incidence of cancer increases with advancing age, but the biological behavior of cancer is known to be less aggressive in elderly people. Thus, the proliferative activity and extent of apoptosis of cancer cells were assessed in samples from 163 cases of colorectal cancer focusing on the age of patients, using Ki-67 labeling index (LI) and apoptotic index (AI) by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling method and staining for activated caspase-3.

The Ki-67 LI of colorectal cancer ranged from 2.33 to 80.4% (mean 32.2%), while the AI ranged from 0.00 to 14.8% (mean 3.57%). Concerning the aging effect, linear and positive correlations were found for the Ki-67 LI of cancer with age (p<0.05) and the AI of cancer with age (p<0.05). However, in normal colorectal mucosa, aging of patients revealed a significant correlation only with the AI but not with the Ki-67 LI. The AI in earlier stages of cancers (stages 0 and 1) revealed a significant difference between younger cases (age<65) and more elderly cases (age≥65) (p<0.05), however, the Ki-67 LI did not exhibit a significant difference. Therefore, an increased frequency of apoptosis in colorectal cancer tissues, especially in the earlier stages, may possibly explain the slower growth of colorectal cancers in the elderly. Next, the expressions of several regulatory molecules for the proliferation/apoptosis of tumor cells were determined. The results demonstrated a tendency for stronger and more frequent expressions of c-myc, Bak and Bax despite a rather weaker expression of Bcl-2 in cancer tissues from the elderly compared with those from the younger patients. The potential roles of these regulatory molecules on age-change in the proliferation/apoptosis of colorectal cancers are discussed.     

Pathological characteristics of early to advanced gallbladder carcinoma and extrahepatic cholangiocarcinoma

Biliary tract cancer (cancer of gallbladder and extrahepatic bile duct) is the most common malignancy of the biliary tract, and is considered to be a high‐grade malignancy. In this study, we reviewed 293 gallbladder cancers and 102 bile duct cancers for clarifying growth and invasion of the extrahepatic bile duct cancer. Only 10.5% (9/86) of the early gallbladder cancers showed lymphatic invasion, but neither venous invasion nor lymph node metastasis was noted in the early cancers. 70.6% (207/293) of the gallbladder cases were pT2‐3 cancers, and frequently showed lymphatic/venous/perineural invasion and/or lymph node metastasis. 12.7% (13/102) of the extrahepatic bile duct cancers were pTis or pT1 cancers, which were categorized as early cancers. Only 15.4% (2/13) of the early cancer showed vascular/perineural invasion and/or lymph node metastasis. The majority (87.3%) of the extrahepatic bile duct cases was pT2‐3 cancers, and frequently showed vascular/perineural invasion and/or lymph node metastasis. We also examined intramural invasion patterns; i.e. intramural invasion patterns were defined as infiltrative growth (IG) type, and destructive growth (DG) type. The overall survival rate of the gallbladder cancer patients with the DG type was significantly lower than that of the patients with the IG type, associated with frequent lymphatic/venous invasion and/or lymph node metastasis. Therefore, pathological characteristics are important for clinical manifestation of the gallbladder/extrahepatic bile duct cancers.