WEBVTT 00:00.000 --> 00:30.000 position:50% align:top line:0% *This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.* 00:02.440 --> 00:02.760 Thank you. 00:05.140 --> 00:05.460 Yeah, 00:05.840 --> 00:06.240 thank you. 00:06.240 --> 00:09.200 DR sessions and members of 00:09.210 --> 00:10.960 the symposium. 00:11.740 --> 00:13.990 When clinicians 00:13.990 --> 00:16.550 extrapolate from the characteristics 00:16.560 --> 00:19.430 of a disease presented in patients, 00:19.440 --> 00:19.800 you know, 00:19.800 --> 00:22.580 seen by them to a larger universe. 00:22.650 --> 00:25.150 Their their vision may be clouded by 00:25.150 --> 00:26.460 ethnocentrism. 00:26.840 --> 00:29.200 The tendency to regard ones 00:29.200 --> 00:32.110 experience as the standard of reference 00:32.640 --> 00:35.400 epidemiology may provide a 00:35.400 --> 00:37.960 corrective for ethnocentrism 00:38.340 --> 00:40.970 and we will try to sketch some of 00:40.970 --> 00:43.840 the epidemiological highlights of 00:43.850 --> 00:46.260 colon cancer in the hope that 00:46.740 --> 00:49.160 will provide a perspective in which 00:49.840 --> 00:52.440 the clinicians can place their 00:52.440 --> 00:54.040 own contributions 00:54.940 --> 00:57.550 based on patient observation. 00:58.040 --> 00:58.840 For this purpose, 00:58.840 --> 01:01.430 we will draw on information assembled 01:01.440 --> 01:04.080 from international comparisons, 01:04.090 --> 01:05.310 time trends, 01:05.310 --> 01:07.600 migrant populations and the 01:07.610 --> 01:09.880 precursor lesions of polyps, 01:09.890 --> 01:12.400 uh which have just been so 01:12.410 --> 01:15.350 uh ably discussed 01:16.140 --> 01:16.650 then, 01:17.540 --> 01:20.430 uh the probable reason for failure to make 01:20.440 --> 01:23.220 greater progress in the ideology of large 01:23.230 --> 01:25.700 bowel cancer is that virtually all the 01:25.700 --> 01:28.260 studies have been conducted in the high risk 01:28.260 --> 01:31.200 populations of north America and western 01:31.200 --> 01:31.660 europe. 01:32.040 --> 01:33.820 For a firmer grip on the 01:33.820 --> 01:36.510 epidemiology that might lead to 01:36.510 --> 01:38.420 ideological hypotheses. 01:38.840 --> 01:41.180 one Ought to begin with 01:41.180 --> 01:42.880 international comparisons. 01:43.340 --> 01:46.000 The initial evidence for striking inter 01:46.000 --> 01:48.370 population variations and risk 01:48.380 --> 01:50.670 came from comparative studies of 01:50.680 --> 01:51.770 mortality. 01:51.780 --> 01:54.380 These have been uh elaborated more 01:54.380 --> 01:57.080 recently by incidents data from 01:57.080 --> 01:59.590 tumor registries made possible by 01:59.600 --> 02:01.900 extension of the network of tumor 02:01.900 --> 02:03.990 registries to cover some 02:03.990 --> 02:06.510 populations and eastern 02:06.510 --> 02:09.280 europe asia africa 02:09.280 --> 02:10.760 and south America. 02:11.340 --> 02:14.210 Uh some of the results first 02:14.210 --> 02:14.960 slide please. 02:17.340 --> 02:19.850 And I guess if you can Yeah, 02:20.440 --> 02:21.600 that's fine. 02:21.850 --> 02:24.250 This is a selected 02:24.840 --> 02:26.980 uh group of comparisons of 02:26.990 --> 02:28.060 populations. 02:28.440 --> 02:31.110 The purpose is to show the 02:31.120 --> 02:33.730 magnitude of range of differences 02:33.730 --> 02:36.720 between high and low risk populations 02:36.720 --> 02:39.670 on the order of six or seven fold. 02:39.680 --> 02:42.150 This particular comparison is 02:42.640 --> 02:45.050 for colon cancer incidents, 02:45.050 --> 02:47.570 that is a sigmoid. 02:47.570 --> 02:48.260 And above. 02:49.200 --> 02:50.760 The next slide 02:51.880 --> 02:53.250 gives the 02:54.540 --> 02:56.160 that was for males. 02:56.540 --> 02:59.450 They results for females 02:59.840 --> 03:02.560 show the same range 03:02.560 --> 03:04.860 of inter population difference. 03:05.640 --> 03:06.360 The 03:08.270 --> 03:10.930 results no 03:10.930 --> 03:13.860 fall into roughly three 03:13.860 --> 03:16.350 groups that is high risk 03:16.350 --> 03:17.910 represented by Connecticut, 03:17.920 --> 03:18.860 new Zealand. 03:19.240 --> 03:22.210 Then we have a medium 03:22.220 --> 03:24.400 intermediate risks in most of western 03:24.400 --> 03:25.280 europe, 03:25.290 --> 03:27.940 United Kingdom Norway and 03:27.940 --> 03:30.880 then lower risks 03:30.880 --> 03:32.960 in eastern europe 03:33.740 --> 03:36.320 Finland at 03:36.330 --> 03:38.760 japan and south America. 03:39.440 --> 03:41.710 The comparable data 03:41.720 --> 03:44.630 on carcinoma direct. 03:44.630 --> 03:46.160 Um The next slide 03:47.540 --> 03:50.270 for males chose 03:50.270 --> 03:52.800 the the same type 03:52.800 --> 03:55.600 of of variation 03:55.600 --> 03:58.300 although a little narrower range. 03:58.620 --> 04:01.060 And the next slide on females 04:01.440 --> 04:03.150 rectum females 04:03.640 --> 04:06.640 substantially the same 04:06.770 --> 04:09.480 picture the same. 04:09.800 --> 04:12.340 This similar 04:12.340 --> 04:14.770 ordering for colon and 04:14.770 --> 04:17.320 rectum can be shown in the next 04:17.320 --> 04:17.960 slide. 04:19.740 --> 04:22.700 Uhh this slide We have one 04:22.700 --> 04:25.160 axis incidents rights for rectum. 04:25.940 --> 04:28.710 The other axis giving the incidence 04:28.710 --> 04:29.750 rates for colon. 04:30.540 --> 04:31.260 Uh 04:33.140 --> 04:33.950 the 04:36.340 --> 04:39.320 uh rights 04:39.320 --> 04:40.460 for 04:42.340 --> 04:43.860 for males, 04:44.740 --> 04:47.160 we can look up the 04:48.040 --> 04:50.460 and for females. 04:54.940 --> 04:55.410 No, 04:55.410 --> 04:58.230 the uh the white the yellow dot 04:58.230 --> 05:01.230 is the uh the females and the red 05:01.230 --> 05:02.720 triangle as a team. 05:02.730 --> 05:05.680 And you can see that uh fairly 05:05.690 --> 05:07.660 regular ordering. 05:08.540 --> 05:09.760 Now some of the 05:11.930 --> 05:14.850 enter registry variation in 05:15.440 --> 05:17.490 column rectum ratios. 05:17.490 --> 05:20.260 We can bring this point out better in the next slide. 05:22.140 --> 05:23.660 This gives the 05:25.440 --> 05:28.350 directly ratios of the colon 05:28.350 --> 05:30.800 cancer incidence to the rectum 05:30.800 --> 05:31.560 incidents. 05:32.440 --> 05:35.040 Uhh and for 05:35.040 --> 05:37.580 virtually all of the the 05:37.590 --> 05:38.760 populations, 05:39.190 --> 05:41.450 this ratio does exceed 05:41.940 --> 05:42.810 unity. 05:42.980 --> 05:45.260 There are certain differences which 05:46.140 --> 05:49.020 you can see for females ratio 05:49.020 --> 05:51.160 generally being higher for 05:52.040 --> 05:53.080 that sex. 05:54.040 --> 05:56.950 Uh part of this variation that you 05:56.950 --> 05:59.910 see in this slide might be uh due to 05:59.910 --> 06:02.810 different practices and assignment of tumors 06:02.810 --> 06:05.050 close to the sigmoid fletcher. 06:05.540 --> 06:08.070 But classification artifacts seem 06:08.070 --> 06:10.500 unlikely to be the sole 06:10.510 --> 06:11.970 explanations. 06:11.980 --> 06:14.590 And this set of results raises the 06:14.590 --> 06:17.390 possibility of population differences 06:17.400 --> 06:20.370 in anatomical localization of uh 06:20.380 --> 06:21.460 bowel tumours. 06:21.840 --> 06:24.450 The localization of tumors within the 06:24.450 --> 06:27.300 colon has been reported to very in 06:27.300 --> 06:28.460 the literature, 06:28.840 --> 06:30.670 High risk populations, 06:30.680 --> 06:31.590 high risk. 06:31.660 --> 06:33.930 Most of the tumors appear to be on 06:33.930 --> 06:35.620 the left side. 06:35.620 --> 06:37.790 A typical result being the 06:37.800 --> 06:40.600 63% of such 06:40.600 --> 06:43.150 a colon tumors in England. 06:43.160 --> 06:45.770 While in uh low risk 06:45.780 --> 06:46.730 uh countries, 06:46.730 --> 06:49.420 the tumors seem to be concentrated on the 06:49.430 --> 06:50.390 right side. 06:50.400 --> 06:52.570 Uh typical result being uh 06:52.580 --> 06:55.150 65% right sided uh 06:55.540 --> 06:57.660 localizations in Cali 06:57.800 --> 06:58.660 Colombia. 06:59.440 --> 06:59.990 In fact, 07:00.000 --> 07:02.800 when we array the registries in ascending 07:02.800 --> 07:05.520 order of overall cancer incidence, 07:05.940 --> 07:08.750 there is a concentration of tumors 07:09.210 --> 07:12.150 in the sigmoid segment 07:12.840 --> 07:15.390 uh in those registries with the 07:15.390 --> 07:17.110 highest overall incidents, 07:17.120 --> 07:19.480 uh I don't have a slide to show this, 07:19.480 --> 07:21.560 but the data from Connecticut 07:21.940 --> 07:23.950 show this concentration. 07:24.340 --> 07:27.260 And if we took really low risk populations such 07:27.260 --> 07:29.560 as the Bombay and Cali, 07:30.040 --> 07:33.040 we would have very 07:33.040 --> 07:35.260 little concentration in this 07:36.570 --> 07:37.860 part of the, 07:38.540 --> 07:39.350 of the colon. 07:40.240 --> 07:42.610 Uh The next 07:42.620 --> 07:43.250 figure, 07:44.240 --> 07:47.060 uhh describes the sex 07:47.060 --> 07:49.460 ratios for colon cancer incidents. 07:50.130 --> 07:52.920 The point to be made here is that in high 07:52.920 --> 07:54.510 risk populations, 07:54.510 --> 07:57.450 the male female ratio tends to 07:57.450 --> 07:58.760 be close to unity. 07:59.060 --> 08:01.560 There's an obvious exception here. 08:02.040 --> 08:03.580 The Hawaiian japanese, 08:03.580 --> 08:05.660 which we will discuss a little later. 08:06.340 --> 08:08.670 While in the lower risk populations, 08:08.670 --> 08:10.890 there is a tendency for female 08:10.900 --> 08:12.020 predominance. 08:12.640 --> 08:15.460 The picture for rectum is quite 08:15.470 --> 08:16.420 different. 08:16.430 --> 08:19.320 Higher rates for males prevail at all levels 08:19.320 --> 08:19.820 of risk. 08:19.830 --> 08:20.760 Next slide, 08:23.240 --> 08:25.860 you can see the there's only 08:25.870 --> 08:27.310 one exception 08:29.840 --> 08:30.560 for rectum. 08:31.740 --> 08:34.550 Uh The sex 08:34.550 --> 08:35.070 ratios, 08:35.070 --> 08:35.620 however, 08:35.620 --> 08:38.290 based on summary age adjusted rates 08:38.300 --> 08:41.180 obscure some rather interesting sex 08:41.180 --> 08:42.880 age interactions. 08:42.890 --> 08:45.620 Uh When we look at the populations at 08:45.630 --> 08:48.050 two extremes of uh colon 08:48.050 --> 08:50.420 cancer risk, 08:50.430 --> 08:52.780 we see some different sex 08:52.780 --> 08:55.250 behavior in the 08:55.740 --> 08:57.060 age specific rates. 08:57.060 --> 08:57.750 Next slide 09:01.640 --> 09:04.600 Connecticut and colleague Connecticut being 09:04.600 --> 09:06.350 a high risk population. 09:06.840 --> 09:08.360 We can see that the 09:08.940 --> 09:11.630 rates for the two 09:11.630 --> 09:14.240 sexes are very close 09:14.240 --> 09:17.170 together and with a slight 09:17.180 --> 09:20.170 male predominance at the older age is 09:20.740 --> 09:23.460 in Cali on the other hand, 09:23.840 --> 09:26.390 we can see Quite a definite 09:26.400 --> 09:28.990 female predominance after age 09:29.000 --> 09:30.250 65. 09:32.630 --> 09:35.240 The pattern of 09:35.250 --> 09:38.000 uh of uh just depicted 09:38.000 --> 09:40.770 for Cali and other low risk 09:40.770 --> 09:43.120 communities at corresponds 09:43.130 --> 09:46.050 closely to that observed for the subset 09:46.440 --> 09:49.340 Of seeking a sending tumors 09:49.340 --> 09:51.200 in higher risk 09:51.210 --> 09:54.070 populations uh for both the female 09:54.070 --> 09:56.770 predominance after age 65 has 09:56.770 --> 09:58.510 established this next slide, 09:58.520 --> 09:59.060 please. 10:01.940 --> 10:04.800 We had the result for colleagues and 10:04.800 --> 10:06.290 in Norway, 10:06.290 --> 10:08.750 which is one of the intermediate risk there 10:09.140 --> 10:11.330 for sake um and ascending. 10:11.460 --> 10:12.750 We do get this 10:13.440 --> 10:16.150 crossover with higher female 10:16.150 --> 10:18.520 risks and the older age 10:18.520 --> 10:19.160 range. 10:20.340 --> 10:22.740 The in 10:22.750 --> 10:24.650 contrast the 10:26.240 --> 10:29.080 we get a similarity in contours of the age 10:29.080 --> 10:31.750 specific rates for colon and 10:31.760 --> 10:33.250 rectum cancers. 10:33.260 --> 10:35.720 Using the rectal sigmoid lectures the 10:35.730 --> 10:38.600 dividing line Uh 10:38.610 --> 10:41.300 in very high risk populations where the 10:41.310 --> 10:44.120 male rights after 65 are clearly 10:44.120 --> 10:44.480 higher. 10:44.480 --> 10:45.000 In both. 10:45.000 --> 10:45.660 Next slide 10:48.240 --> 10:50.730 we have this male 10:50.730 --> 10:51.960 predominance, 10:52.340 --> 10:55.060 but it's a more marked 10:55.440 --> 10:56.960 for your rectum. 10:58.740 --> 11:01.340 From these and related observations, 11:01.340 --> 11:04.070 we make injector that the entity colon 11:04.070 --> 11:07.050 cancer may have at least two separate components seek 11:07.050 --> 11:09.820 him ascending and as using as a 11:09.820 --> 11:12.410 label and sigmoid rectum. 11:12.420 --> 11:15.040 It appears to be the latter which accounts for the 11:15.040 --> 11:17.570 enhanced risks observed in the north 11:17.570 --> 11:19.150 America and western europe. 11:19.940 --> 11:21.810 If environmental factors are 11:21.810 --> 11:22.960 responsible, 11:23.340 --> 11:25.960 the intensity of exposures and resultant 11:25.960 --> 11:28.260 incidents may have been changing over time 11:28.740 --> 11:31.390 Connecticut is one of the registries in which we 11:31.390 --> 11:33.700 have information on this point. 11:33.980 --> 11:34.840 Next slide, 11:34.850 --> 11:35.360 please. 11:36.940 --> 11:39.570 Uhh in 11:40.240 --> 11:43.150 in Connecticut for the sigmoid, 11:44.540 --> 11:46.660 I'm looking at the two 11:47.340 --> 11:50.320 time period Ends of the 15 Year Time 11:50.330 --> 11:50.660 Period. 11:51.130 --> 11:54.120 The male predominance appears to 11:54.130 --> 11:56.560 be a little more firmly established. 11:57.540 --> 11:59.060 Uhh next slide 12:01.440 --> 12:03.710 These for transfers and 12:03.710 --> 12:06.470 descending in the later time 12:06.480 --> 12:07.010 period. 12:07.020 --> 12:09.900 This friend to male dominance 12:09.930 --> 12:11.450 seems to be going on. 12:11.970 --> 12:13.160 Next slide 12:15.140 --> 12:17.150 for Sikkim and descending. 12:17.540 --> 12:20.230 Males have not become dominant yet. 12:20.240 --> 12:22.550 But you can see that the gap is 12:22.560 --> 12:23.450 narrowing. 12:24.440 --> 12:26.560 So uh 12:27.440 --> 12:30.410 one might speculate if if we can turn 12:30.410 --> 12:33.310 the incidents in the United 12:33.310 --> 12:35.430 States as an 12:35.430 --> 12:36.360 epidemic. 12:37.040 --> 12:39.960 one can speculate if this 12:39.960 --> 12:42.800 epidemic will reach a climax with 12:42.800 --> 12:44.920 the presence of a male 12:44.920 --> 12:47.360 predominance in the 12:47.840 --> 12:50.450 lesions in the Sikh um and 12:50.840 --> 12:52.660 a sending no colon. 12:53.740 --> 12:56.560 Uh In addition to these inter population 12:56.560 --> 12:57.420 comparisons, 12:57.420 --> 12:59.810 it's useful to discuss 13:00.340 --> 13:02.390 changes which have appeared in 13:02.390 --> 13:05.140 certain migrant populations 13:05.940 --> 13:08.620 when the colon cancer 13:08.620 --> 13:10.900 experience of the Hawaiian japanese is 13:10.900 --> 13:13.860 contrasted with that for 13:13.860 --> 13:16.260 japan and US white, 13:16.270 --> 13:18.920 a displacement and risks as can be observed. 13:18.920 --> 13:19.560 Next slide, 13:23.240 --> 13:25.830 it's this is the baseline for 13:25.830 --> 13:26.750 japan. 13:27.330 --> 13:29.120 The line for US whites, 13:29.120 --> 13:30.660 the host populations. 13:31.240 --> 13:34.200 And you can see the uh 13:34.210 --> 13:37.080 positioning of the mortality rates 13:37.080 --> 13:39.850 for the the migrants 13:39.860 --> 13:41.220 generation themselves, 13:41.220 --> 13:44.200 the esa and their native born descendants among 13:44.200 --> 13:47.070 males has been pushed up towards the 13:47.070 --> 13:47.270 U. 13:47.270 --> 13:47.540 S. 13:47.540 --> 13:47.750 Right? 13:48.140 --> 13:50.400 This tendency is 13:50.830 --> 13:53.360 less marked for the females 13:53.930 --> 13:56.080 and it is this 13:56.090 --> 13:57.680 phenomenon I believe, 13:57.680 --> 14:00.050 which produces this unusual 14:00.440 --> 14:03.400 sex ratio for the Hawaiian japanese, 14:03.400 --> 14:06.190 which occurred in an earlier slide where there 14:06.190 --> 14:09.060 was a excess of 14:09.940 --> 14:12.910 risk of colon cancer among 14:12.910 --> 14:15.250 the male population. 14:15.840 --> 14:18.820 There's uh suggests that there is 14:18.820 --> 14:21.070 a greater male volatility and 14:21.070 --> 14:23.930 biological uh response to 14:23.940 --> 14:25.950 changed conditions 14:27.240 --> 14:28.350 in the 14:32.240 --> 14:35.150 a latent period between exposure 14:36.540 --> 14:38.940 and development of neo plas. 14:38.940 --> 14:41.640 Ums one of course tries to look 14:41.650 --> 14:44.560 for precursor lesions and to use 14:44.560 --> 14:47.460 such information and attempt to transform 14:47.460 --> 14:49.860 the epidemiology of colon cancer 14:50.240 --> 14:52.620 into the epidemiology of a 14:52.630 --> 14:53.810 precursor lesion. 14:53.820 --> 14:56.590 The Early landmark in this direction 14:56.590 --> 14:59.560 was a paper by Helwig in the 1940s, 14:59.940 --> 15:02.810 which looked at adenomas polyps 15:02.810 --> 15:05.170 as a candidate precursor. 15:05.640 --> 15:08.580 His line of attack was too search for 15:08.580 --> 15:11.500 congruence is in the anatomical distribution 15:11.510 --> 15:13.550 of cancers and polyps. 15:14.440 --> 15:16.960 Uh time doesn't allow to 15:16.970 --> 15:19.530 consider the findings of 15:19.540 --> 15:20.240 people, 15:20.250 --> 15:20.500 you know, 15:20.500 --> 15:22.990 following Hellwig and the different 15:23.000 --> 15:25.750 interpretations of these uh findings. 15:26.140 --> 15:26.770 It started, 15:26.770 --> 15:29.460 I'm going to make a general observation 15:30.140 --> 15:31.160 as I say, 15:31.160 --> 15:33.950 that they were unable to resolve the 15:34.340 --> 15:36.670 the polyps cancer congruence 15:36.680 --> 15:39.350 problem and related issues with 15:39.360 --> 15:41.970 observations solely from 15:41.980 --> 15:43.890 high risk populations. 15:43.900 --> 15:46.250 Uh This is probably not surprising 15:46.640 --> 15:49.620 since when you have little background variation in 15:49.620 --> 15:52.370 the distribution and biologic behaviors of 15:52.370 --> 15:52.970 lesions, 15:53.030 --> 15:55.550 it becomes very difficult to 15:55.560 --> 15:58.180 detect patterns and relationships. 15:58.740 --> 16:01.630 A single population might have 16:01.630 --> 16:04.580 permitted test of a very simple palla 16:04.590 --> 16:06.750 cancer models such as the 16:07.240 --> 16:09.490 constant probability of transition 16:09.490 --> 16:11.810 independent of anatomical 16:11.810 --> 16:12.830 localization. 16:12.830 --> 16:15.440 But when you have more complicated 16:15.440 --> 16:16.220 models, 16:16.230 --> 16:16.570 uh, 16:16.570 --> 16:19.430 I think that you need greater 16:19.440 --> 16:22.290 background variation and experience 16:23.140 --> 16:24.450 for this reason, 16:24.460 --> 16:25.860 studies of 16:26.240 --> 16:29.180 precursor lesions needed to 16:29.180 --> 16:31.700 be carrying out carried out in populations 16:31.700 --> 16:34.450 with widely different colon cancer 16:34.460 --> 16:35.220 incidents. 16:35.230 --> 16:35.720 Uh, 16:35.730 --> 16:38.490 since hell Wigs data were on record. 16:38.500 --> 16:41.260 Uh Professor Korea and 16:41.270 --> 16:43.660 Colombia and I decided that 16:44.140 --> 16:47.070 uh work of this type should be 16:47.070 --> 16:50.030 done in a low risk population represented 16:50.030 --> 16:52.870 in Cali Colombia and Korea has 16:52.880 --> 16:55.070 published on the study of 16:55.440 --> 16:57.560 Of 1500 16:57.840 --> 16:59.810 bottle specimens from 16:59.820 --> 17:01.650 necropsies there. 17:02.240 --> 17:04.850 The results that I'm going to give 17:05.340 --> 17:08.300 are are 17:08.300 --> 17:11.290 still in the infancy 17:11.290 --> 17:13.440 and they have to be treated as 17:13.450 --> 17:16.450 exploratory and illustrative and certainly 17:16.450 --> 17:18.560 not as uh as definitive. 17:19.240 --> 17:20.500 However, 17:20.820 --> 17:23.780 when we compare these results with 17:23.780 --> 17:24.960 those from Helwig, 17:25.540 --> 17:28.390 from results more recently obtained 17:28.390 --> 17:30.900 in New Orleans by Professor 17:30.900 --> 17:33.560 Strong and his group and 17:34.010 --> 17:36.670 results from 17:37.340 --> 17:40.200 the japanese migrants in Hawaii 17:40.200 --> 17:42.680 and from populations in 17:42.680 --> 17:43.720 japan. 17:43.940 --> 17:46.920 Certain uhh 17:46.930 --> 17:49.670 patterns emerge next slide. 17:51.240 --> 17:53.970 Uh This compares the 17:53.980 --> 17:56.550 distribution of aveeno 17:56.550 --> 17:59.350 metis and hyper plastic polyps in the 17:59.350 --> 18:01.530 autopsy specimens in 18:01.910 --> 18:04.910 college Korea when he did the 18:04.910 --> 18:05.890 work because 18:07.140 --> 18:09.960 uh concentrated 18:09.960 --> 18:12.050 on adenomas polyps, 18:12.060 --> 18:14.910 he felt that uh this 18:14.910 --> 18:17.330 distribution would turn out to be 18:17.340 --> 18:20.080 quite different than in the United States is 18:20.080 --> 18:23.040 reported by Helwig and indeed it is uh 18:23.050 --> 18:25.770 you uhh first one 18:25.770 --> 18:28.580 explanation these location of 18:28.580 --> 18:31.230 these lesions are plotted with 18:31.230 --> 18:34.060 respect to distance from the anus. 18:34.640 --> 18:37.110 And uh but they on this 18:37.110 --> 18:39.640 particular scale uh they're plotted in 18:39.640 --> 18:41.580 terms of relative distance. 18:41.590 --> 18:44.410 Uh that is converting the total length 18:44.410 --> 18:47.140 of the of the ball 18:47.150 --> 18:49.960 from the illegal cycle valve to the 18:50.560 --> 18:53.050 To the and this is 100%. 18:53.440 --> 18:56.100 So that most of the of 18:56.100 --> 18:58.900 the tumors up to the sigmoid 18:58.900 --> 19:01.520 fletcher would be in this the 19:01.530 --> 19:03.860 1st 10 19:04.640 --> 19:07.230 From 10 to 90% on this 19:07.680 --> 19:08.770 note. 19:09.140 --> 19:12.090 For then there is a similar 19:12.100 --> 19:14.850 distribution for hyper plastic 19:14.860 --> 19:15.360 polyps. 19:15.360 --> 19:18.200 There is a concentration in 19:18.200 --> 19:20.770 the in the 19:20.780 --> 19:23.700 rectum as one would expect. 19:23.710 --> 19:26.480 But there are some surprising features about 19:26.490 --> 19:28.560 this which I'll return to 19:29.540 --> 19:31.390 when we compare 19:31.630 --> 19:34.480 Cali with Hellwig and with new 19:34.480 --> 19:37.360 Orleans in the 19:37.740 --> 19:40.340 the high risk colon population than the U. 19:40.340 --> 19:40.650 S. 19:40.650 --> 19:42.960 Have a higher prevalence of 19:42.960 --> 19:45.600 adenomas polyps at all ages in both 19:45.600 --> 19:46.260 sexes. 19:46.640 --> 19:47.790 And this difference is 19:48.050 --> 19:50.580 accentuated particularly for 19:50.580 --> 19:53.410 females when you limit the contrast 19:53.420 --> 19:55.460 to multiple at anomalies. 19:55.840 --> 19:58.420 That is multiplicity is is not a 19:58.420 --> 20:00.960 feature in a uh this low 20:00.960 --> 20:03.850 risk uh population in new 20:03.850 --> 20:04.400 Orleans. 20:04.400 --> 20:07.340 The adenomas were also larger and they 20:07.340 --> 20:09.750 had a much higher 20:09.760 --> 20:12.720 proportion of adenomas 20:12.720 --> 20:14.460 with a tapia's 20:15.540 --> 20:18.500 also a much higher proportion of 20:18.500 --> 20:19.860 the new Orleans. 20:19.860 --> 20:22.840 Adenomas were concentrated in 20:22.840 --> 20:25.070 the in the 20:25.070 --> 20:27.430 sigmoid recto 20:27.440 --> 20:29.770 sigmoid area. 20:30.640 --> 20:32.260 Uh This uh 20:32.740 --> 20:35.090 is replicated now in 20:35.090 --> 20:38.000 the observations on the japanese 20:38.010 --> 20:38.590 migrants. 20:38.590 --> 20:40.890 That is the Hawaiian japanese. 20:40.890 --> 20:43.460 Haven't adenomas polyp distribution 20:43.840 --> 20:45.820 closely resembling that. 20:45.820 --> 20:48.340 And all these features exhibited by 20:48.350 --> 20:50.670 blacks and whites in New Orleans. 20:51.340 --> 20:54.020 The observations from 20:54.020 --> 20:56.060 Japan taken in Miyagi 20:56.070 --> 20:58.690 prefecture have a 20:58.700 --> 21:01.590 polyp distribution for adenomas which 21:01.600 --> 21:04.490 resembles that of the low risk 21:04.490 --> 21:05.690 college population. 21:05.690 --> 21:08.690 That is uh we now have uh to 21:08.690 --> 21:11.260 a high low risk contrast which show 21:11.260 --> 21:13.350 essentially the same results. 21:14.240 --> 21:17.220 Now when Korea did the work on 21:17.220 --> 21:19.730 hyper plastic polyps in Colombia, 21:19.730 --> 21:22.680 I think that he was doing it primarily for 21:22.680 --> 21:25.520 sake of completeness recording the observations and 21:25.530 --> 21:27.360 uh those plus you know, 21:27.360 --> 21:28.700 juvenile polyps. 21:29.440 --> 21:31.570 He like other pathologists. 21:32.340 --> 21:34.860 I didn't think that 21:35.640 --> 21:38.040 uh there was going to be any no 21:38.040 --> 21:40.570 relationship uh demonstrated 21:40.580 --> 21:43.160 with with the tumors and 21:43.170 --> 21:45.170 the location of the 21:45.840 --> 21:47.900 these hyper plastic pileups. 21:47.900 --> 21:50.640 Got uh 21:50.650 --> 21:53.400 And I think the 21:53.400 --> 21:55.810 feeling was based on on 21:55.810 --> 21:58.460 the Marfa logic evidence, 21:59.040 --> 22:00.180 but big, 22:00.190 --> 22:01.370 big surprise. 22:01.840 --> 22:04.460 It turns out that in the 22:05.240 --> 22:07.830 in the Hawaiian japanese and the 22:07.830 --> 22:09.360 native japanese, 22:09.940 --> 22:12.410 that uh there is a great 22:12.420 --> 22:14.800 difference in the distribution 22:14.810 --> 22:17.290 of hyper plastic polyps, 22:17.290 --> 22:19.860 that that is while hyper plastic polyps 22:19.860 --> 22:22.450 are certainly concentrated in the 22:23.020 --> 22:25.850 in the area between the flexion er 22:25.850 --> 22:27.240 and the anus. 22:27.760 --> 22:30.170 There's just a much 22:30.170 --> 22:33.150 greater frequency of such polyps 22:33.150 --> 22:35.800 in the Hawaiian japanese 22:35.810 --> 22:38.230 popular as opposed to 22:38.230 --> 22:38.910 japan. 22:38.910 --> 22:41.730 And this same finding is 22:42.190 --> 22:45.050 emerging from the 22:45.060 --> 22:47.760 comparisons in new Orleans with 22:47.760 --> 22:49.450 the colleagues. 22:49.940 --> 22:52.680 So new Orleans with 22:52.680 --> 22:54.270 the colleagues, 22:54.840 --> 22:57.260 so that while the 22:57.260 --> 22:59.940 pathologists have been slow 22:59.940 --> 23:00.770 to, 23:01.540 --> 23:04.240 I have not have thought that there 23:04.240 --> 23:07.200 was anything in the morphological studies that 23:07.200 --> 23:09.590 would really uh yield 23:09.600 --> 23:11.640 suggestive leads these 23:11.640 --> 23:14.500 epidemiologic comparisons now point to 23:14.510 --> 23:16.350 great differences in these 23:16.840 --> 23:19.740 parents of these hyper plastic. 23:20.440 --> 23:22.850 Just how this will 23:23.170 --> 23:26.170 relate in the long run to the 23:26.640 --> 23:28.560 distribution of 23:29.040 --> 23:31.580 of all right 23:31.590 --> 23:33.960 of of rectal 23:33.970 --> 23:36.310 cancers remains to be seen. 23:36.590 --> 23:39.450 My feeling is that uh 23:40.040 --> 23:42.640 that these type of observations are 23:42.640 --> 23:45.410 likely to uh stimulate uh 23:45.420 --> 23:47.080 work in the area of, 23:47.090 --> 23:47.350 you know, 23:47.350 --> 23:49.890 cell kinetics which uh your doctor 23:49.890 --> 23:52.600 lukin will be discussing 23:52.610 --> 23:55.360 this afternoon and that 23:55.940 --> 23:58.830 uh this 23:58.830 --> 24:01.530 will be one 24:01.530 --> 24:04.530 area in which the say the colon 24:04.530 --> 24:07.260 cancer task force and the colon cancer, 24:07.740 --> 24:08.290 you know, 24:08.290 --> 24:10.730 segment of the cancer institute will be 24:10.980 --> 24:13.770 spending much more time on 24:14.640 --> 24:17.460 so to uhh 24:17.650 --> 24:20.580 summarized uh 24:20.590 --> 24:23.310 we have might have proposed 24:23.320 --> 24:25.960 the following as a working model 24:26.640 --> 24:29.330 in low risk populations where the disease 24:29.330 --> 24:31.940 is endemic Colon cancers are 24:31.940 --> 24:33.380 concentrated in the Sikh, 24:33.380 --> 24:35.980 um and ascending colon female cases 24:35.980 --> 24:38.910 are preponderant and most of 24:38.910 --> 24:41.730 the rise to the maximum incidence level 24:41.730 --> 24:44.060 occurs by age 50 55. 24:44.940 --> 24:45.420 If, 24:45.430 --> 24:47.850 when a new ideological factor 24:48.640 --> 24:50.170 is introduced, 24:50.540 --> 24:52.850 A transition from an endemic to an 24:52.850 --> 24:55.780 epidemic phases first expressed as a 24:55.780 --> 24:58.670 rise in sigmoid cancers among older 24:58.670 --> 25:00.260 men over 55. 25:00.940 --> 25:03.440 A rise in female sigmoid cancer 25:03.450 --> 25:05.920 follows later and the time lag is 25:05.920 --> 25:08.380 reinforced by a tendency for these female 25:08.380 --> 25:11.160 cases to appear at somewhat older ages. 25:11.940 --> 25:14.560 As exposures to a 25:14.560 --> 25:17.140 suspect undefined ideological 25:17.150 --> 25:20.020 factor becomes more intense and prolonged. 25:20.030 --> 25:22.600 A later phase is characteristically 25:22.600 --> 25:25.170 arise and seek them and ascending colon 25:25.170 --> 25:27.790 cancers more marked for males and for 25:27.790 --> 25:30.270 females so that the female excess 25:30.640 --> 25:33.480 and seek um cancer prevailing under endemic 25:33.480 --> 25:36.210 conditions is as dis 25:36.210 --> 25:37.560 minister diminished. 25:38.840 --> 25:41.430 The present 25:41.430 --> 25:44.190 observations on the prevalence of polyps 25:44.190 --> 25:44.670 suggests. 25:44.670 --> 25:47.430 Some link with the level of colon cancer 25:47.430 --> 25:49.680 incidents in the given communities, 25:49.680 --> 25:52.380 not only with respect to magnitude of prevalence, 25:52.400 --> 25:55.220 but also with respect to distribution by 25:55.220 --> 25:55.730 age, 25:55.730 --> 25:56.120 sex, 25:56.120 --> 25:58.980 anatomical localization and 25:58.990 --> 26:00.180 multiplicity. 26:00.190 --> 26:03.020 I think these clues lead to 26:03.030 --> 26:05.660 uh some ideas on 26:05.670 --> 26:08.470 ideology which I think time 26:08.470 --> 26:10.880 will prevent uh me from 26:10.890 --> 26:13.460 discussing this 26:13.460 --> 26:14.060 morning, 26:14.840 --> 26:15.770 but 26:17.740 --> 26:20.350 there is the possibility I think 26:20.350 --> 26:23.310 of of of linking 26:23.310 --> 26:25.490 up studies of 26:25.490 --> 26:28.060 ideology and testing them with respect 26:28.540 --> 26:30.980 to this uh difference in 26:30.980 --> 26:33.960 anatomical distribution for both. 26:34.740 --> 26:35.460 Um 26:37.540 --> 26:40.120 polyps and cancers. 26:40.540 --> 26:43.290 one thing which is occurring 26:43.290 --> 26:45.440 and this japanese 26:45.440 --> 26:48.360 population which is very suitable for 26:48.940 --> 26:51.230 epidemiologic studies of 26:51.240 --> 26:53.310 dietary hypotheses. 26:53.860 --> 26:56.820 And I won't go into it any further than 26:56.820 --> 26:57.610 to say this, 26:57.610 --> 27:00.520 that the associations with 27:00.530 --> 27:03.110 uh some of the differences between the case and 27:03.110 --> 27:05.850 control series appear to be 27:05.860 --> 27:08.740 much more marked for those cancers 27:08.740 --> 27:11.480 which are uh 27:11.490 --> 27:13.240 in the rectal sigmoid, 27:13.240 --> 27:13.440 you know, 27:13.440 --> 27:16.220 fletcher and above that is such associations 27:16.220 --> 27:19.130 for tumors in the in the lower rectum 27:19.130 --> 27:21.880 is uh is virtually 27:21.890 --> 27:24.810 absent so that we may be 27:24.810 --> 27:27.390 able to uh bring 27:27.390 --> 27:29.770 about a synthesis of uh 27:30.240 --> 27:32.930 of studies and the 27:32.940 --> 27:35.700 traditional epidemiology logic 27:35.710 --> 27:38.350 type represented by case control 27:38.740 --> 27:41.140 and prospective cohort 27:41.140 --> 27:43.710 studies with findings 27:44.340 --> 27:47.290 uhh made by uh no 27:47.290 --> 27:49.340 geographical a 27:49.350 --> 27:50.460 pathologist. 27:54.040 --> 27:54.360 Okay, 27:57.040 --> 27:57.270 okay.