several reports have shown the process from early to advanced gastric cancer , and macroscopic morphological progression has been observed by retrospective image analysis . however , a prospective follow - up of gradual morphological changes is markedly rare because the conditions allowing such a follow - up are limited . in general , gastric cancer remains in the mucosa for a long time and once it infiltrates to the submucosal layer the growth speed is accelerated and the tumor develops to advanced cancer . we here report the progression process in a case followed up over time from early to advanced gastric cancer and discuss the growth and development pattern . an 89-year - old male complaining of epigastric pain underwent upper gastrointestinal endoscopy . a shallow depressed lesion with redness was observed at the anterior wall of the upper gastric body , and iic - type early gastric cancer was diagnosed . there was no abnormality in laboratory data . due to severe heart complications ( pacemaker implanted ) , surgical resection of gastric cancer was not feasible . the asa physical status classification system gave category 3 . due to his old age and complications , he and his family hoped for a periodic follow - up without intensive treatment . endoscopy was carried out every 6  months to 1  year as a follow - up . no abnormality other than mild anemia . in 1999 , at 89  years old , he complained of mild epigastric pain at the clinic visit , but there was no physical finding . abdominal ultrasonography and abdominal computed tomography revealed liver cysts but no swollen lymph nodes . due to severe heart disease , it was decided that he was unable to undergo surgery , and he had been followed up periodically since then . laboratory data showed no abnormality . in 1999 , ca19 - 9 and cea showed normal values of 3.2 and 9.19 , respectively , but ca19 - 9 was slightly elevated since 2005 and it was 376.3 in 2007 . he was confirmed dead due to heart failure in december 2007 at 97  years old . between 1999 and 2002 , a shallow depressed lesion 2  cm in size was confirmed at the anterior wall of the upper gastric body . the lesion was a little smaller than 20  mm in size ( fig . a slightly depressed lesion with redness was found at the upper body of the stomach . e the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . g ulcer and elevation around the lesion became marked endoscopic findings of gastric cancer natural course . a slightly depressed lesion with redness was found at the upper body of the stomach . e the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . g ulcer and elevation around the lesion became marked furthermore , 3  years later , endoscopy showed irregularity on the depressed surface with elevated boundaries , which suggested submucosal invasion ( fig . despite the elevated boundaries , the size of the tumor remained constant and a little larger than 20  mm . in 2005 , the ulcer became deeper and the boundaries were even higher . the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . the size increased to 40  mm . in 2007 , the ulcer area and elevated boundaries enlarged even more . a biopsy specimen showed well to moderately differentiated adenocarcinoma in 2002 ( fig .  2a , b).fig . b high - power view of biopsy specimen a biopsy specimen revealed well to moderately differentiated adenocarcinoma . b high - power view of biopsy specimen images exhibiting early cancer were observed between 1999 and 2002 and thereafter the ulcer was deeper with heightened boundaries , which suggested the tendency of deeper invasion . eventually , no metastasis was found by imaging examinations but an increase in ca19 - 9 suggested lymph node metastasis . an 89-year - old male complaining of epigastric pain underwent upper gastrointestinal endoscopy . a shallow depressed lesion with redness was observed at the anterior wall of the upper gastric body , and iic - type early gastric cancer was diagnosed . there was no abnormality in laboratory data . due to severe heart complications ( pacemaker implanted ) , surgical resection of gastric cancer was not feasible . the asa physical status classification system gave category 3 . due to his old age and complications , he and his family hoped for a periodic follow - up without intensive treatment . endoscopy was carried out every 6  months to 1  year as a follow - up . in 1999 , at 89  years old , he complained of mild epigastric pain at the clinic visit , but there was no physical finding . abdominal ultrasonography and abdominal computed tomography revealed liver cysts but no swollen lymph nodes . due to severe heart disease , it was decided that he was unable to undergo surgery , and he had been followed up periodically since then . laboratory data showed no abnormality . in 1999 , ca19 - 9 and cea showed normal values of 3.2 and 9.19 , respectively , but ca19 - 9 was slightly elevated since 2005 and it was 376.3 in 2007 . he was confirmed dead due to heart failure in december 2007 at 97  years old . between 1999 and 2002 , a shallow depressed lesion 2  cm in size was confirmed at the anterior wall of the upper gastric body . the lesion was a little smaller than 20  mm in size ( fig . a slightly depressed lesion with redness was found at the upper body of the stomach . e the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . g ulcer and elevation around the lesion became marked endoscopic findings of gastric cancer natural course . a slightly depressed lesion with redness was found at the upper body of the stomach . e the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . g ulcer and elevation around the lesion became marked furthermore , 3  years later , endoscopy showed irregularity on the depressed surface with elevated boundaries , which suggested submucosal invasion ( fig . despite the elevated boundaries , the size of the tumor remained constant and a little larger than 20  mm . in 2005 , the ulcer became deeper and the boundaries were even higher . the lesion slightly enlarged to 25  mm . in 2006 , the size of the lesion and the ulcer area enlarged . the size increased to 40  mm . in 2007 , the ulcer area and elevated boundaries enlarged even more . a biopsy specimen showed well to moderately differentiated adenocarcinoma in 2002 ( fig .  2a , b).fig . b high - power view of biopsy specimen a biopsy specimen revealed well to moderately differentiated adenocarcinoma . b high - power view of biopsy specimen images exhibiting early cancer were observed between 1999 and 2002 and thereafter the ulcer was deeper with heightened boundaries , which suggested the tendency of deeper invasion . eventually , no metastasis was found by imaging examinations but an increase in ca19 - 9 suggested lymph node metastasis . there have been a number of retrospective studies on morphological changes from early to advanced gastric cancer . when the lesion becomes larger , the proportion of the lesion with deeper invasion increases . considering this , the growth speed of small early gastric cancer is slow and once it exceeds 4  cm in size and infiltrates to the proper muscle layer , it typically enlarges rapidly in a short period of time . nakamura et al .   reported that it took 7  years on average to progress from m to sm cancer and 23  years from sm to advanced cancer . in the present case , it is unclear when an intramucosal lesion first appeared , but the lesion remained within the mucosal layer at least for 4  years from the first detection , and it was suggested that endoscopic mucosal resection was indicated at that time . the tumor invaded to sm and to mp , and it took 3  years to exhibit the appearance of advanced cancer , which was consistent with previous reports . tsukuma   reported that early gastric cancer showed a relatively long natural history in general and the median duration of those who remained in the early stage was estimated as 44  months . since 2005 when the tumor was confirmed to be advanced cancer , it had dramatically enlarged to a size twice that 1  year previously by endoscopy . as factors influencing the growth of early gastric cancer , age , morphological types , presence of ulcer , and histology have been reported . retrospective studies on gastric cancer revealed that iic - type gastric cancer was the most frequently observed early lesion , the period that iic lesions remained m cancer was long and ulceration was the cause of slow growth . since most colorectal cancers exhibit an elevated type and it is easier to analyze them by x - ray retrospectively , it is possible to calculate the growth speed . matsui et al .   reported the results of an x - ray study that showed small colorectal cancer developed according to certain exponential functions ( diameter  =  12.5    2 or volume  =  1    10  2 ) , where t is the time in months . according to this equation , the doubling time of early colorectal cancer was calculated as 26  months . in general , tumor doubling time  =  ( days    log2)/[3    log ( tumor diameter at this time / tumor diameter at former time ) ] . according to this calculation , the doubling time of this tumor was 298  days . on the other hand , it is known that fibrosis arising from repeated ulceration and scarring in a malignant cycle inhibits the growth of gastric cancer , and sm cancer grows faster than m cancer . judging from the size , the tumor remained 2025  mm in size for 34  years , and then enlarged threefold in 3  years . in the present case , although the tumor had been early gastric cancer 8  years before , it grew to advanced cancer in 8  years . endoscopic findings suggest that the tumor was m cancer in 1999 when it was first detected . in 2003 , it showed a change and resembled a submucosal tumor ( smt ) , which indicated sm infiltration . then , the smt - like elevation was recognized as elevated boundaries and it was diagnosed as advanced cancer in 2005 . endoscopic findings showed that the tumor showed the morphology of early gastric cancer for about 5  years , and then developed to advanced cancer . lymph node metastasis seemed to be from 2005 , as ca19 - 9 was gradually increased from that time . reported that peripheral venous ca19 - 9 levels were significantly higher in patients with positive lymph node staining with immunohistochemical study than in those without it . since early gastric cancer remained at the early stage for about 8  years , m cancer detected 7  years previously could have been treated by endoscopic resection . recently endoscopic treatment has been widely employed for early gastric cancer , in particular small gastric cancer , while the necessity of the treatment is discussed . in japan , an aging society , the detection rate of early gastric cancer in the elderly is high . in the elderly , although the necessity of treatment is often discussed , conclusions have not been reached , because estimation of life expectancy is difficult . considering the natural history of gastric cancer , the period of gastric cancer which remains in the mucosa is long . considering the growth curve of the intramucosal lesion , it is necessary to deal appropriately with each case , such as a cut end - positive case , and it is suggested that follow - up is a reasonable option . endoscopic treatment should have been possible until 1999 , but it was impossible in 2003 . however , no appetite loss due to bleeding from the lesion or stenosis was observed and the macroscopic appearance revealed early gastric cancer for as long as about 5  years . even after advanced cancer was diagnosed , vertical development , rather than horizontal expansion , was mainly observed . periodic annual follow - ups allowed observations of macroscopic time - course changes in invasion of the gastric cancer to deeper layers . time - course changes in invasion to deeper layers were expressed as the height of elevated boundaries . although there are a number of reports on the natural history of gastric cancer , they are mostly retrospective reports and the change is estimated based on the endoscopic pictures at the first detection and several years previously . this is a rare and valuable case report that periodically followed up growth and morphology of gastric cancer for 8  years and showed the growth pattern of gastric cancer in detail .
we experienced a case of gastric cancer that was prospectively followed up for 8  years . with severe heart disease , the patient did not wish surgery or anticancer drug treatment . 
 after informed consent was obtained , he was followed up for 8  years . 
 he received upper gastrointestinal endoscopy every year , which revealed iic early gastric cancer , and biopsy showed well differentiated adenocarcinoma . 
 a flat and mildly depressed lesion with redness was observed on endoscopy , exhibiting typical morphology of iic - type early gastric cancer . 
 the appearance of iic m cancer was observed macroscopically from 2000 to 2003 . 
 four years later , surface irregularity with ulceration appeared . 
 then , the whole lesion was elevated , which suggested submucosal invasion , and the tumor exhibited the morphology of iia  +  iic or type 3 . 
 the ulcer became deeper and elevated boundaries were formed . 
 horizontal expansion of the flat lesion was mild , while invasion to deeper layers was predominant . eventually , he died of heart failure . 
 estimated m cancer was observed for about 3  years , followed by invasion to deeper layers . taken together , this is a valuable case that followed up the manner of invasion to deeper layers over time from early to advanced gastric cancer .