1 00:00:06,773 --> 00:00:09,209 WELCOME TO TODAY'S CC GRAND 2 00:00:09,209 --> 00:00:16,721 ROUNDS AT THE CENTER. 3 00:00:16,721 --> 00:00:22,293 AS YOU CAN SEE FROM THE SCREEN, 4 00:00:22,293 --> 00:00:27,165 THE ACTIVITY CODE IS 50,546, 5 00:00:27,165 --> 00:00:31,369 PLEASE TEXT THIS PHONE NUMBER TO 6 00:00:31,369 --> 00:00:32,103 RECEIVE CREDIT FOR THIS 7 00:00:32,103 --> 00:00:32,604 PRESENTATION. 8 00:00:32,604 --> 00:00:36,774 AND ALSO LIKE TO PROVIDE YOU 9 00:00:36,774 --> 00:00:37,542 FEEDBACK ON TODAY'S LECTURE. 10 00:00:37,542 --> 00:00:40,278 YOU WILL SEE THE QR CODE TO DO 11 00:00:40,278 --> 00:00:40,545 THAT. 12 00:00:40,545 --> 00:00:42,413 FOR THOSE OF YOU WHO CAME IN 13 00:00:42,413 --> 00:00:44,148 PERSON, THERE IS ACTUALLY A 14 00:00:44,148 --> 00:00:47,185 PAPER WHERE YOU CAN SCAN IT AS 15 00:00:47,185 --> 00:00:50,321 YOU EXIT AND FOR THOSE APPLYING 16 00:00:50,321 --> 00:00:52,790 FOR CME, YOU WILL RECEIVE THAT 17 00:00:52,790 --> 00:00:54,459 VIA E-MAIL AND THAT IS WHAT WE 18 00:00:54,459 --> 00:00:56,794 WILL USE TO PROVIDE FEEDBACK FOR 19 00:00:56,794 --> 00:00:58,029 THIS PRESENTATION, ALSO ALLOWS 20 00:00:58,029 --> 00:01:00,198 YOU TO SUBMIT PROPOSALS FOR 21 00:01:00,198 --> 00:01:07,171 CASES THAT WOULD MAKE GREAT 22 00:01:07,171 --> 00:01:08,406 TOPICS FOR NEXT BAND FROM 23 00:01:08,406 --> 00:01:09,941 ROUNDS. 24 00:01:09,941 --> 00:01:13,878 FOR THE SPEAKERS, SCROLL DOWN ON 25 00:01:13,878 --> 00:01:17,515 YOUR SCREEN AND CLICK ON THE 26 00:01:17,515 --> 00:01:19,017 LIVE FEEDBACK BUTTON FOR YOUR 27 00:01:19,017 --> 00:01:21,553 QUESTIONS FOR THE SPEAKERS AND 28 00:01:21,553 --> 00:01:23,054 WE WILL DO THAT TOGETHER WITH 29 00:01:23,054 --> 00:01:25,189 THE QUESTIONS THAT COME FROM THE 30 00:01:25,189 --> 00:01:28,126 AUDIENCE HERE. 31 00:01:28,126 --> 00:01:32,330 SO TODAY'S CPC CASE IS A 32 00:01:32,330 --> 00:01:34,365 PHENOMENAL CASE HOW HERE AT THE 33 00:01:34,365 --> 00:01:36,768 CLINICAL CENTER, THE IMPACTFUL 34 00:01:36,768 --> 00:01:38,536 CLINICAL RESEARCH THAT HAS MAJOR 35 00:01:38,536 --> 00:01:41,339 IMPLICATIONS IN THE HEALTH OF 36 00:01:41,339 --> 00:01:44,409 PATIENTS AND PLUS ACCOMPANIED BY 37 00:01:44,409 --> 00:01:45,577 IMPORTANT FUNDAMENTAL RESEARCH 38 00:01:45,577 --> 00:01:47,278 ASSOCIATED WITH THIS SO THE 39 00:01:47,278 --> 00:01:51,149 PRESENTERS FOR TODAY'S TALK ARE 40 00:01:51,149 --> 00:01:54,986 JEREMY DAVIS, SURGICAL ON COIN 41 00:01:54,986 --> 00:02:00,124 PROGRAM AT NCI, Dr. KO RMAN AT 42 00:02:00,124 --> 00:02:04,762 IDK, Dr. KIM, A STAFF PATH 43 00:02:04,762 --> 00:02:12,403 GIFT AND RESEARCH PHYSICIANS AND 44 00:02:12,403 --> 00:02:16,207 GRACE-ANN FASAYE, COUNSELOR AT 45 00:02:16,207 --> 00:02:17,408 THE GENETICS BRANCH AT THE 46 00:02:17,408 --> 00:02:20,445 CENTERS FOR RESEARCH AT NCI. 47 00:02:20,445 --> 00:02:24,649 WITH NO FURTHER ADIEU, WE WILL 48 00:02:24,649 --> 00:02:26,117 BEGIN OUR TALK TODAY. 49 00:02:26,117 --> 00:02:33,491 LET'S GET IT GOING. 50 00:02:33,491 --> 00:02:34,592 >> OKAY, Dr. HELLER IS HERE SO 51 00:02:34,592 --> 00:02:35,693 WE CAN START. 52 00:02:35,693 --> 00:02:35,960 [LAUGHTER] 53 00:02:35,960 --> 00:02:38,529 >> I AM GOING TO START OFF TODAY 54 00:02:38,529 --> 00:02:38,963 WITH A DEFINITION. 55 00:02:38,963 --> 00:02:41,599 THAT IS JUST TO GET EVERYBODY ON 56 00:02:41,599 --> 00:02:42,333 THE SAME PAGE. 57 00:02:42,333 --> 00:02:45,603 SO WE'RE GOING TO TALK TODAY 58 00:02:45,603 --> 00:02:50,575 ABOUT GASTRIC CANCER BUT 59 00:02:50,575 --> 00:02:51,743 SPECIFICALLY ADENOCARCINOMA 60 00:02:51,743 --> 00:02:57,348 WHICH ACCOUNTS FOR 95 PERCENT OF 61 00:02:57,348 --> 00:02:58,116 ALL GASTRIC CANCERS ON THE 62 00:02:58,116 --> 00:02:59,083 LINING OF THE STOMACH. 63 00:02:59,083 --> 00:03:03,321 WE WILL TALK ABOUT DIFFUSE TYPE 64 00:03:03,321 --> 00:03:06,257 CANCERS, A POORLY COHESIVE 65 00:03:06,257 --> 00:03:16,801 CANCER THAT HAS SIGNANT RING 66 00:03:16,801 --> 00:03:20,972 CELLS WHICH ARE A PORTION OF 67 00:03:20,972 --> 00:03:25,143 CELLS BUT NOT ONLY IN THE 68 00:03:25,143 --> 00:03:30,581 STOMACH, SIGNET AND THEN CDH1 69 00:03:30,581 --> 00:03:32,183 EDITING CODES WE SEE IN PROTEINS 70 00:03:32,183 --> 00:03:35,553 AND WE WILL TALK A LOT ABOUT 71 00:03:35,553 --> 00:03:38,322 CDH1 TODAY AND I KNOW WE'LL 72 00:03:38,322 --> 00:03:39,991 START WITH THE CASE 73 00:03:39,991 --> 00:03:41,125 PRESENTATION. 74 00:03:41,125 --> 00:03:43,261 THIS IS AN 11-YEAR-OLD BOY WITH 75 00:03:43,261 --> 00:03:46,564 A DIAGNOSIS OF ADHD AND AUTISM 76 00:03:46,564 --> 00:03:48,399 SPECTRUM STORED. 77 00:03:48,399 --> 00:03:50,301 HE HAD A GENETIC WORKUP FOR 78 00:03:50,301 --> 00:03:53,337 THESE CONDITIONS AND IT LED TO 79 00:03:53,337 --> 00:03:58,009 AN INCIDENTAL FINDING OF A 80 00:03:58,009 --> 00:03:59,844 GERMLINE CDH1 PATHOGENIC VARIANT 81 00:03:59,844 --> 00:04:01,612 AND GRACE-ANN WILL TALK ABOUT 82 00:04:01,612 --> 00:04:03,781 THAT A LITTLE LATER WHEN SHE 83 00:04:03,781 --> 00:04:06,084 TALKS ABOUT THE GENETICS. 84 00:04:06,084 --> 00:04:08,820 RELEVANT HISTORY, HE WAS BORN 85 00:04:08,820 --> 00:04:13,858 PREMATURELY, SPENT A MONTH ON A 86 00:04:13,858 --> 00:04:18,863 VENT LATER, SPEECH DELAY, AUTISM 87 00:04:18,863 --> 00:04:22,233 SPECTRUM DISORDER AND ADHD. 88 00:04:22,233 --> 00:04:24,936 HE IS IN THE 6TH GRADE, LIVES AT 89 00:04:24,936 --> 00:04:27,205 HOME WITH HIS PARENTS AND 90 00:04:27,205 --> 00:04:29,941 SIBLINGS, GOES TO OT AND HAS 91 00:04:29,941 --> 00:04:33,311 THERAPY BUT OTHERWISE LOOKS TO 92 00:04:33,311 --> 00:04:35,646 BE A REGULAR 6TH GRADE KID. 93 00:04:35,646 --> 00:04:40,918 SO HE NOW HAS THIS DIAGNOSIS OF 94 00:04:40,918 --> 00:04:43,588 A GERMLINE PATHOGENIC VARIANT IN 95 00:04:43,588 --> 00:04:44,355 THE CDH1 GENE. 96 00:04:44,355 --> 00:04:46,424 THE PARENTS KNOW THIS BUT 97 00:04:46,424 --> 00:04:47,225 WEREN'T PLANNING ON DOING 98 00:04:47,225 --> 00:04:50,094 ANYTHING AT THE MOMENT BUT HE 99 00:04:50,094 --> 00:04:51,462 DEVELOPED THIS NONSPECIFIC 100 00:04:51,462 --> 00:04:54,065 ABDOMINAL PAIN, NOT EATING MUCH 101 00:04:54,065 --> 00:04:55,466 AND THE MOM WAS CONCERNED AND 102 00:04:55,466 --> 00:04:58,936 TOOK HIM TO THE PEDIATRICIAN AND 103 00:04:58,936 --> 00:05:03,374 KNOWING HE HAD THIS GERMLINE 104 00:05:03,374 --> 00:05:04,108 VARIANT, THEY PERFORMED AN 105 00:05:04,108 --> 00:05:06,043 ENDOSCOPY IN JANUARY OF LAST 106 00:05:06,043 --> 00:05:07,779 YEAR. 107 00:05:07,779 --> 00:05:10,548 THEY TOOK MULTIPLE BIOPSIES BUT 108 00:05:10,548 --> 00:05:14,485 ONE OF THEM CALLED GASTRIC 109 00:05:14,485 --> 00:05:15,820 CARCINOMA, DIFFUSE TYPE AND 110 00:05:15,820 --> 00:05:18,089 Dr. KIM WILL SHOW THE 111 00:05:18,089 --> 00:05:18,890 PATHOLOGY LATER. 112 00:05:18,890 --> 00:05:21,325 HE WAS IN ANOTHER STATE AND WAS 113 00:05:21,325 --> 00:05:22,960 WORKED UP AT A CHILDREN'S 114 00:05:22,960 --> 00:05:24,729 HOSPITAL AND AS YOU WOULD DO 115 00:05:24,729 --> 00:05:26,998 WITH A GASTRIC CANCER, THEY GOT 116 00:05:26,998 --> 00:05:31,269 A PET SCAN TO LOOK FOR EVIDENCE 117 00:05:31,269 --> 00:05:34,672 OF METASTATIC DISEASE WHICH WAS 118 00:05:34,672 --> 00:05:36,307 NEGATIVE. 119 00:05:36,307 --> 00:05:37,241 IN GASTRIC CANCER, WE PUT A 120 00:05:37,241 --> 00:05:40,945 CAMERA IN THE BELLY, LOOK AROUND 121 00:05:40,945 --> 00:05:46,884 AND MAKE SURE THERE IS NO OCCULT 122 00:05:46,884 --> 00:05:49,587 OF GASTRIC CANCER IN THE 123 00:05:49,587 --> 00:05:52,256 PERINEUM AND THEN HE HAD A PORT 124 00:05:52,256 --> 00:05:53,457 PLACED AND STARTED ON 125 00:05:53,457 --> 00:05:53,858 CHEMOTHERAPY. 126 00:05:53,858 --> 00:05:56,561 I WON'T GO INTO THE DETAILS BUT 127 00:05:56,561 --> 00:05:58,663 THE STANDARD TREATMENT FOR 128 00:05:58,663 --> 00:06:01,566 GASTRIC CANCER IN THE UNITED 129 00:06:01,566 --> 00:06:03,167 STATES IS PREOPERATIVE 130 00:06:03,167 --> 00:06:06,304 CHEMOTHERAPY, SURGERY AND 131 00:06:06,304 --> 00:06:08,406 POSTOPERATIVE CHEMOTHERAPY. 132 00:06:08,406 --> 00:06:18,316 AND THE POST STANCE IS 5-OP 133 00:06:18,316 --> 00:06:19,817 CHEMOTHERAPY, USUALLY TWO 134 00:06:19,817 --> 00:06:22,386 CYCLES, SURGERY AND THEN TWO 135 00:06:22,386 --> 00:06:23,621 CYCLES -- MAYBE I AM WRONG, IT 136 00:06:23,621 --> 00:06:26,724 IS FOUR CYCLES AND TWO CYCLES. 137 00:06:26,724 --> 00:06:32,797 SHOULD HAVE GOTTEN THAT ONE 138 00:06:32,797 --> 00:06:35,099 RIGHT, HUH? 139 00:06:35,099 --> 00:06:38,302 HIS MOTHER WANTED A SECOND 140 00:06:38,302 --> 00:06:41,105 OPINION AFTER THE FIRST ROUND OF 141 00:06:41,105 --> 00:06:42,440 CHEMOTHERAPY AND I WILL PAUSE 142 00:06:42,440 --> 00:06:44,141 THERE A BIT WHILE WE SET UP THE 143 00:06:44,141 --> 00:06:45,776 REST OF THE DISCUSSION. 144 00:06:45,776 --> 00:06:47,979 HE WAS DIAGNOSED WITH GASTRIC 145 00:06:47,979 --> 00:06:52,383 CANCER AND TALKING ABOUT ADEN 146 00:06:52,383 --> 00:06:53,451 OCARCINOMA. 147 00:06:53,451 --> 00:06:56,187 WORLDWIDE IT IS VERY COMMON BUT 148 00:06:56,187 --> 00:06:58,756 ONLY 35,000 CASES IN THE UNITED 149 00:06:58,756 --> 00:07:00,391 STATES, ACCOUNTS FOR ONLY 150 00:07:00,391 --> 00:07:01,692 1 PERCENT OF THE NEW CANCER 151 00:07:01,692 --> 00:07:03,828 CASES IN THE U.S. 152 00:07:03,828 --> 00:07:09,333 BUT FIVE-YEAR SURVIVAL IS POOR. 153 00:07:09,333 --> 00:07:10,601 35PERCENT, FIVE-YEAR SURVIVAL SO 154 00:07:10,601 --> 00:07:13,738 NOT A GOOD CANCER IF THERE EVER 155 00:07:13,738 --> 00:07:16,073 WAS ONE. 156 00:07:16,073 --> 00:07:18,242 AN INDIVIDUAL'S LIFETIME RISK OF 157 00:07:18,242 --> 00:07:20,177 DEVELOPING GASTRIC CANCER IS 158 00:07:20,177 --> 00:07:23,748 ABOUT .8 PERCENT AND THIS IS 159 00:07:23,748 --> 00:07:25,383 SEAR DATA I PULLED DOWN 160 00:07:25,383 --> 00:07:25,683 YESTERDAY. 161 00:07:25,683 --> 00:07:28,319 YOU CAN SEE THE MEDIAN AGE IS 162 00:07:28,319 --> 00:07:28,519 68. 163 00:07:28,519 --> 00:07:30,154 VERY FEW PATIENTS UNDER THE AGE 164 00:07:30,154 --> 00:07:32,123 OF 45 ARE DIAGNOSED WITH STOMACH 165 00:07:32,123 --> 00:07:34,692 CANCER SO IT IS LIKE A LOT OF 166 00:07:34,692 --> 00:07:37,795 CANCERS, A DISEASE OF AGING OR 167 00:07:37,795 --> 00:07:39,363 OF THE AGED. 168 00:07:39,363 --> 00:07:41,899 THE DIFFUSE TYPE GASTRIC CANCER, 169 00:07:41,899 --> 00:07:46,938 THERE IS INTESTINAL TYPE AND 170 00:07:46,938 --> 00:07:49,573 DIFFUSE TYPE AND THIS GOES BACK 171 00:07:49,573 --> 00:07:53,878 TO THE 1960S BUT IS TRUE TODAY. 172 00:07:53,878 --> 00:07:55,146 DIFFUSE TYPE DOESN'T FORM 173 00:07:55,146 --> 00:07:56,347 MASSES, IT IS ILL FILL TRADED 174 00:07:56,347 --> 00:07:58,249 AND YOU WILL SEE THE PICTURES IN 175 00:07:58,249 --> 00:07:59,951 A LITTLE BIT. 176 00:07:59,951 --> 00:08:02,787 BUT WHAT IS INTERESTING IS THIS 177 00:08:02,787 --> 00:08:04,822 IS INCREASING IN YOUNGER AND 178 00:08:04,822 --> 00:08:06,791 FEMALE GROUPS SO THAT RED LINE 179 00:08:06,791 --> 00:08:08,092 IS THE CIRCLE THAT REPRESENTS 180 00:08:08,092 --> 00:08:10,027 YOUNG WOMEN AND THAT NUMBER IS 181 00:08:10,027 --> 00:08:11,495 GOING UPWARD. 182 00:08:11,495 --> 00:08:14,632 SO WHY DO WE STUDY DIFFUSE 183 00:08:14,632 --> 00:08:15,232 CANCER? 184 00:08:15,232 --> 00:08:17,201 BECAUSE IT IS DIAGNOSED LATE IN 185 00:08:17,201 --> 00:08:19,971 THE UNITED STATES AND MOST 186 00:08:19,971 --> 00:08:21,639 PEOPLE ARE DIAGNOSED -- SORRY, 187 00:08:21,639 --> 00:08:25,109 THIS IS SURVIVAL -- WHEN CANCER 188 00:08:25,109 --> 00:08:25,876 IS DIAGNOSED LATE. 189 00:08:25,876 --> 00:08:29,280 SO IF WE DIAGNOSE IT EARLY, 190 00:08:29,280 --> 00:08:30,748 SURVIVAL IS ABOUT 75 PERCENT. 191 00:08:30,748 --> 00:08:35,419 WE DIAGNOSE IT WITH REGIONAL OR 192 00:08:35,419 --> 00:08:37,455 DISTANT SPREAD, SURVIVAL DROPS 193 00:08:37,455 --> 00:08:37,788 PRECIPITOUSLY. 194 00:08:37,788 --> 00:08:44,762 THERE ARE NO STRATEGIES THERE, 195 00:08:44,762 --> 00:08:46,163 NO PRECURSIVE LESIONS, AND 196 00:08:46,163 --> 00:08:48,432 THERAPIES ARE LARGELY 197 00:08:48,432 --> 00:08:48,966 INEFFECTIVE. 198 00:08:48,966 --> 00:08:51,669 AND WHAT IS TRUE TODAY IS 199 00:08:51,669 --> 00:08:54,338 1-3 PERCENT OF GASTRIC CANCERS 200 00:08:54,338 --> 00:08:56,040 ARE CONSIDERED INHERITABLE. 201 00:08:56,040 --> 00:08:58,042 THESE NUMBERS AREN'T PERFECT BUT 202 00:08:58,042 --> 00:09:00,044 WE THINK THEY ARE ABOUT RIGHT. 203 00:09:00,044 --> 00:09:03,247 Dr. KIM IS GOING TO TALK ABOUT 204 00:09:03,247 --> 00:09:05,416 PATHOLOGY BUT I WANT TO REMIND 205 00:09:05,416 --> 00:09:06,283 EVERYONE FROM WHAT THEY HAVE 206 00:09:06,283 --> 00:09:09,453 SEEN IN THE PAST, THIS IS THE 207 00:09:09,453 --> 00:09:10,755 STOMACH, THE LUMEN IS ON THE TOP 208 00:09:10,755 --> 00:09:10,955 SIDE. 209 00:09:10,955 --> 00:09:14,892 WHEN WE TALK ABOUT MUCOSA, WE'RE 210 00:09:14,892 --> 00:09:17,728 TALKING ABOUT THE HE WILL TEAL 211 00:09:17,728 --> 00:09:23,601 Y'ALL LAYER AND LAMINA PROPRIA. 212 00:09:23,601 --> 00:09:27,071 ANY CANCER IN THIS STAGE IS 21A, 213 00:09:27,071 --> 00:09:31,008 WHAT WE WILL TALK ABOUT TODAY, 214 00:09:31,008 --> 00:09:35,946 THEN WE HAVE THE MUCOSA AND 215 00:09:35,946 --> 00:09:36,280 SUBMUCOSA. 216 00:09:36,280 --> 00:09:40,518 ANY CANCERS IN THIS AREA ARE 217 00:09:40,518 --> 00:09:42,620 T1B. 218 00:09:42,620 --> 00:09:45,189 THEN YOU HAVE THE THICKER LAYER, 219 00:09:45,189 --> 00:09:48,159 THE OUTSIDE OF THE STOMACH SO AS 220 00:09:48,159 --> 00:09:49,994 YOU PROGRESS THROUGH THE WALLS 221 00:09:49,994 --> 00:09:52,329 OR LAYERS OF THE STOMACH, 222 00:09:52,329 --> 00:09:53,798 CANCERS BECOME HIGHER IN THE 223 00:09:53,798 --> 00:09:56,767 TUMOR STAGE. 224 00:09:56,767 --> 00:10:02,206 AND THEN LASTLY, CDH1 APPROACH, 225 00:10:02,206 --> 00:10:06,977 THIS IS EPITHELIAL AND A CALCIUM 226 00:10:06,977 --> 00:10:08,112 DEPENDENT PROTEIN AND THAT IS 227 00:10:08,112 --> 00:10:15,252 HOW IT GOT ITS NAMES. 228 00:10:15,252 --> 00:10:17,321 IT DEMONSTRATES WITH CELL CAN I 229 00:10:17,321 --> 00:10:22,293 GOALING AND THE LAYER IN BLUE 230 00:10:22,293 --> 00:10:25,930 CONNECTS TO THE ALPHABETA INSIDE 231 00:10:25,930 --> 00:10:31,735 THE CELL AND THEN THE 232 00:10:31,735 --> 00:10:32,169 CYTOSKELETON. 233 00:10:32,169 --> 00:10:35,439 SO THE LOSS HERE IS KNOWN TO 234 00:10:35,439 --> 00:10:41,745 DISRUPT ARCHITECTURE, SELF 235 00:10:41,745 --> 00:10:42,413 POLARITY AND ADHESION. 236 00:10:42,413 --> 00:10:45,416 AND WHAT WE WILL TALK ABOUT 237 00:10:45,416 --> 00:10:48,119 TODAY IS LOSS OF FUNCTION 238 00:10:48,119 --> 00:10:51,288 MUTATIONS THAT ARE CONSIDERED 239 00:10:51,288 --> 00:10:54,291 PATHOGENIC MEANING THEY WILL 240 00:10:54,291 --> 00:10:55,759 LEAD TO DISEASE. 241 00:10:55,759 --> 00:10:57,661 SO THE DIFFUSE TYPE OF CANCER WE 242 00:10:57,661 --> 00:11:04,935 WILL TALK ABOUT IS AN AUTOD 243 00:11:04,935 --> 00:11:06,770 OMINANT SET OF CANCERS, WE WILL 244 00:11:06,770 --> 00:11:10,474 FOCUS ON GAS STRICK CANCER TODAY 245 00:11:10,474 --> 00:11:12,109 AND GERMLINE CDH1, LOSS OF 246 00:11:12,109 --> 00:11:14,712 FUNCTION VARIANTS ARE THE MOST 247 00:11:14,712 --> 00:11:15,079 COMMON CAUSE. 248 00:11:15,079 --> 00:11:22,386 OTHER VAR AGAINST ASSOCIATED 249 00:11:22,386 --> 00:11:27,391 CONTAIN PT1, NOT TALKING ABOUT 250 00:11:27,391 --> 00:11:29,059 THAT. 251 00:11:29,059 --> 00:11:30,661 ONLY ONE IN 10,000 BIRTHS BUT 252 00:11:30,661 --> 00:11:34,798 THE TAKEAWAY IS IF YOU HAVE A 253 00:11:34,798 --> 00:11:37,201 PATHOGENIC GERMLINE OF CDH1, THE 254 00:11:37,201 --> 00:11:39,537 REMOVAL OF THE ENTIRE STOMACH TO 255 00:11:39,537 --> 00:11:41,906 PREVENT STOMACH CANCER IS 256 00:11:41,906 --> 00:11:43,874 RECOMMENDED AT THE AGE OF 20 TO 257 00:11:43,874 --> 00:11:47,077 30 YEARS AND IF FOR SOME REASON 258 00:11:47,077 --> 00:11:48,712 THE PATIENT DECLINES SURGERY OR 259 00:11:48,712 --> 00:11:51,682 IS UNFIT FOR SURGERY, THEN 260 00:11:51,682 --> 00:11:56,187 SURVEILLANCE WITH UPPER 261 00:11:56,187 --> 00:12:01,892 ENDOSCOPY IS RECOMMENDED AND 262 00:12:01,892 --> 00:12:05,563 THEN WOMEN WILL LIKELY DEVELOP 263 00:12:05,563 --> 00:12:07,031 LOBULAR BREAST CANCER. 264 00:12:07,031 --> 00:12:10,534 SO THOSE ARE THE TREATMENTS FOR 265 00:12:10,534 --> 00:12:14,371 THOSE WITH CDH1 GERMLINE. 266 00:12:14,371 --> 00:12:23,380 SO Dr. KORMAN WILL TALK ABOUT 267 00:12:23,380 --> 00:12:27,451 THE PATHOGENIC SCREENING AND 268 00:12:27,451 --> 00:12:28,852 THEN Dr. KIM AND GRACE-ANN 269 00:12:28,852 --> 00:12:29,954 WILL TALK ABOUT THE REST. 270 00:12:29,954 --> 00:12:32,189 >> THANK YOU SO MUCH FOR 271 00:12:32,189 --> 00:12:36,160 ALLOWING ME TO TALK ABOUT THIS 272 00:12:36,160 --> 00:12:36,660 VERY DIFFICULT SYNDROME. 273 00:12:36,660 --> 00:12:41,332 I WILL TALK ABOUT THE CHALLENGES 274 00:12:41,332 --> 00:12:42,032 OF ENDOSCOPIC SCREENING AND 275 00:12:42,032 --> 00:12:42,967 SURVEILLANCE. 276 00:12:42,967 --> 00:12:46,704 FIRST WE WILL BEGIN WITH AN 277 00:12:46,704 --> 00:12:48,038 ANATOMY LESSON. 278 00:12:48,038 --> 00:12:55,112 THE STOMACH IS A BAG UNDER THE 279 00:12:55,112 --> 00:12:57,715 ESOPHAGUS FROM AND LEADING TO 280 00:12:57,715 --> 00:13:02,987 THE FINGER THEY ARE AND 281 00:13:02,987 --> 00:13:04,388 DUODENUM. 282 00:13:04,388 --> 00:13:14,932 IT IS FUNDED BY THE PYLORIA, THE 283 00:13:16,867 --> 00:13:17,935 CARDIA, THE OPENINGS, THE 284 00:13:17,935 --> 00:13:20,104 GREATER CURVATURE AND LESSER 285 00:13:20,104 --> 00:13:23,173 CURVATURE AND THEN AN ANT TEAR 286 00:13:23,173 --> 00:13:26,076 WALL AND POSTERIOR WALL. 287 00:13:26,076 --> 00:13:28,479 THE IMAGING TECHNOLOGY WE USE IS 288 00:13:28,479 --> 00:13:35,786 AN UPPER [ ENDOSCOPE, FORWARD 289 00:13:35,786 --> 00:13:39,023 VIEWING, HAS THE VIEW OF 200MM, 290 00:13:39,023 --> 00:13:42,593 THE DIAMETER IS ABOUT 9.2MM. 291 00:13:42,593 --> 00:13:45,496 IT HAS A LIGHT SOURCE, A LENS 292 00:13:45,496 --> 00:13:47,865 WHICH PRODUCES A HIGH DEFINITION 293 00:13:47,865 --> 00:13:48,198 IMAGE. 294 00:13:48,198 --> 00:13:50,567 IT HAS A CHANNEL THROUGH WHICH 295 00:13:50,567 --> 00:13:54,371 WE CAN PUT DEVICES AND IT HAS A 296 00:13:54,371 --> 00:13:58,042 WORKING LENGTH OF ABOUT 10000MM. 297 00:13:58,042 --> 00:14:00,978 THESE PROCEDURES ARE DONE UNDER 298 00:14:00,978 --> 00:14:03,580 ANESTHESIA IN THE UNITED STATES. 299 00:14:03,580 --> 00:14:04,882 FOR GASTRIC CANCER SCREENING 300 00:14:04,882 --> 00:14:08,552 WHICH WAS DONE IN JAPAN AND 301 00:14:08,552 --> 00:14:12,890 ASSOCIATED WITH H.PYLORI, THAT 302 00:14:12,890 --> 00:14:16,260 WAS DONE WITH JUST THERAPY. 303 00:14:16,260 --> 00:14:18,395 THE XENON LIGHT SOURCE PRODUCES 304 00:14:18,395 --> 00:14:21,131 A WHITE LIGHT BUT YOU CAN -- WE 305 00:14:21,131 --> 00:14:23,567 CAN VARY THIS LIGHT BY PUTTING A 306 00:14:23,567 --> 00:14:26,303 FILTER IN WHICH PRODUCES A 307 00:14:26,303 --> 00:14:28,372 DIFFERENT WAVE LENGTH SPECTRUM 308 00:14:28,372 --> 00:14:32,609 CALLED NARROW BAND IMAGING OR 309 00:14:32,609 --> 00:14:33,143 NBI. 310 00:14:33,143 --> 00:14:34,812 THE CHALLENGE THAT WE HAVE IS 311 00:14:34,812 --> 00:14:38,182 BECAUSE OF THE PECULIAR BIOLOGY 312 00:14:38,182 --> 00:14:40,784 OF GASTRIC CANCER DUE TO CDH1. 313 00:14:40,784 --> 00:14:43,420 ON THE LEFT YOU CAN SEE A 314 00:14:43,420 --> 00:14:47,291 CARTOON OF THE AREAS WHERE THE 315 00:14:47,291 --> 00:14:49,493 SIGNET RING CELLS DEVELOP AND 316 00:14:49,493 --> 00:14:50,928 ESSENTIALLY THEY DEVELOP UNDER 317 00:14:50,928 --> 00:14:52,296 THE SURFACE. 318 00:14:52,296 --> 00:14:56,667 SO THE SURFACE MUCOSA APPEARS 319 00:14:56,667 --> 00:14:58,535 SOMEWHAT NORMAL EVEN THOUGH 320 00:14:58,535 --> 00:15:02,806 UNDERNEATH THE SURFACE, ALL 321 00:15:02,806 --> 00:15:03,907 THESE SIGNET RING CELLS ARE 322 00:15:03,907 --> 00:15:05,576 PRESENT AND YOU CAN SEE THIS IS 323 00:15:05,576 --> 00:15:07,945 WHAT IT LOOKS LIKE AND THE PALE 324 00:15:07,945 --> 00:15:08,545 AREAS HERE. 325 00:15:08,545 --> 00:15:10,781 THE REASON I RAISE THE ISSUE OF 326 00:15:10,781 --> 00:15:13,717 PALE AREAS IS THAT THEY ARE 327 00:15:13,717 --> 00:15:17,654 IDENTIFIED DURING VISUAL 328 00:15:17,654 --> 00:15:20,124 INSPECTION IN ENDOSCOPY AND 329 00:15:20,124 --> 00:15:22,359 SEVERAL DOCTORS DATING BACK TO 330 00:15:22,359 --> 00:15:23,961 2005 HAVE SUGGESTED THESE PALE 331 00:15:23,961 --> 00:15:28,465 AREAS HAVE A HIGH PROBABILITY OF 332 00:15:28,465 --> 00:15:29,733 HAVING GASTRIC CANCER. 333 00:15:29,733 --> 00:15:32,202 SO USING HIGH DEFINITION WHITE 334 00:15:32,202 --> 00:15:34,938 LIGHT ON THE LEFT, NARROW BAND 335 00:15:34,938 --> 00:15:37,908 IMAGING ON THE RIGHT, THE IDEA 336 00:15:37,908 --> 00:15:40,577 IS TO IDENTIFY THESE PALE AREAS 337 00:15:40,577 --> 00:15:45,015 AS A METHOD FOR DETECTING EARLY 338 00:15:45,015 --> 00:15:47,484 GASTRIC CANCER. 339 00:15:47,484 --> 00:15:50,020 NOW, WE HAVE A SAMPLING 340 00:15:50,020 --> 00:15:50,521 PROTOCOL. 341 00:15:50,521 --> 00:15:53,323 THIS IS THE CAMBRIDGE PROTOCOL 342 00:15:53,323 --> 00:15:55,759 DEVELOPED IN CAMBRIDGE AND IT 343 00:15:55,759 --> 00:15:58,762 INVOLVES OBTAINING A TOTAL OF 30 344 00:15:58,762 --> 00:16:00,898 BIOPSIES AND THIS IS THE 345 00:16:00,898 --> 00:16:01,265 DISTRIBUTION. 346 00:16:01,265 --> 00:16:02,399 THESE ARE MAPPED SO THAT THEY 347 00:16:02,399 --> 00:16:05,836 ARE FROM THE CARDIA, THE BODY, 348 00:16:05,836 --> 00:16:07,538 THE TRANSITIONAL ZONE WHICH IS 349 00:16:07,538 --> 00:16:11,141 BETWEEN THE BODY AND THE ANTRUM 350 00:16:11,141 --> 00:16:15,412 AND THEN THE ANTRUN AND 351 00:16:15,412 --> 00:16:15,879 PRE-PYLORUS REGION. 352 00:16:15,879 --> 00:16:18,348 THIS IS THE FIRST CASE, AN 353 00:16:18,348 --> 00:16:20,951 11-YEAR-OLD WHO HAD AN ENDOSCOPY 354 00:16:20,951 --> 00:16:21,785 HERE. 355 00:16:21,785 --> 00:16:23,720 THIS IS THE ANTRUM AND YOU WILL 356 00:16:23,720 --> 00:16:25,956 NOTICE THERE ARE NO 357 00:16:25,956 --> 00:16:26,557 ABNORMALITIES ON THE SURFACE. 358 00:16:26,557 --> 00:16:27,791 THIS IS THE BODY OF THE STOMACH. 359 00:16:27,791 --> 00:16:31,128 THIS IS THE CARDIA AND FUNDUS 360 00:16:31,128 --> 00:16:35,132 AND IF YOU LOOK THERE, THERE ARE 361 00:16:35,132 --> 00:16:37,201 SOME SUBTLE CHANGES BUT THERE 362 00:16:37,201 --> 00:16:40,571 AREN'T REALLY SIGNIFICANT 363 00:16:40,571 --> 00:16:41,071 MUCOSAL ABNORMALITIES. 364 00:16:41,071 --> 00:16:42,272 PLAY A LITTLE MORE OF THIS. 365 00:16:42,272 --> 00:16:44,208 YOU CAN SEE THE HEARTBEATING 366 00:16:44,208 --> 00:16:44,808 AGAINST IT. 367 00:16:44,808 --> 00:16:47,478 THIS IS NARROW BAND IMAGING 368 00:16:47,478 --> 00:16:53,183 WHICH EMPHASIZES MUCOSAL DETAIL. 369 00:16:53,183 --> 00:16:55,786 THIS IS WHAT THE BIOPSY LOOKS 370 00:16:55,786 --> 00:16:57,654 LIKE, THESE ARE RANDOM BIOPSIES 371 00:16:57,654 --> 00:16:59,623 DONE IN THE ANTRUM AND THE BODY 372 00:16:59,623 --> 00:17:01,925 OF THE STOMACH SO THIS PATIENT 373 00:17:01,925 --> 00:17:06,830 HAD A TOTAL OF 30BIOPSIES AND 374 00:17:06,830 --> 00:17:09,633 Dr. KIM WILL ADDRESS THE 375 00:17:09,633 --> 00:17:10,000 RESULTS. 376 00:17:10,000 --> 00:17:15,339 GO TO THE NEXT ONE. 377 00:17:15,339 --> 00:17:18,208 WE DEVELOPED UNDER Dr. THEO 378 00:17:18,208 --> 00:17:20,210 HELLER A DIFFERENT SAMPLING 379 00:17:20,210 --> 00:17:23,747 PROTOCOL WHICH WE CALLED THE 380 00:17:23,747 --> 00:17:24,882 BETHESDA PROTOCOL. 381 00:17:24,882 --> 00:17:26,884 THIS IS 88 BIOPSIES. 382 00:17:26,884 --> 00:17:28,852 THIS PROCEDURE TAKES 30 TO 45 383 00:17:28,852 --> 00:17:32,556 MINUTES AND A NORMAL UPPER 384 00:17:32,556 --> 00:17:33,991 ENDOSCOPY WOULD TAKE 10 TO 15 385 00:17:33,991 --> 00:17:36,059 MINUTES SPECIAL THESE ARE HIGHLY 386 00:17:36,059 --> 00:17:36,560 LOCALIZED. 387 00:17:36,560 --> 00:17:45,168 SO YOU CAN SEE THE 88 BIOPSIES, 388 00:17:45,168 --> 00:17:47,070 THE FUNDUS, AND SO WE HAVE A 389 00:17:47,070 --> 00:17:49,006 FAIRLY ACCURATE MAP OF THE 390 00:17:49,006 --> 00:17:50,274 DISTRIBUTION OF THESE 391 00:17:50,274 --> 00:17:50,741 ABNORMALITIES. 392 00:17:50,741 --> 00:17:52,442 THIS IS THE SECOND CASE WHICH 393 00:17:52,442 --> 00:17:55,612 YOU WILL HEAR ABOUT OF A 394 00:17:55,612 --> 00:17:58,549 34-YEAR-OLD FEMALE WHO WAS UNDER 395 00:17:58,549 --> 00:18:01,418 SURVEILLANCE AND SHE HAD BOTH 396 00:18:01,418 --> 00:18:03,420 TARGETED BIOPSIES AND BY 397 00:18:03,420 --> 00:18:05,422 TARGETED, AN ABNORMALITY THAT WE 398 00:18:05,422 --> 00:18:08,292 SEE AND THEN RANDOM BIOPSIES AND 399 00:18:08,292 --> 00:18:09,259 BOTH TARGETED AND RANDOM WERE 400 00:18:09,259 --> 00:18:12,396 POSITIVE AND YOU CAN SEE HERE 401 00:18:12,396 --> 00:18:15,999 PALE AREAS BUT THERE ARE A LOT 402 00:18:15,999 --> 00:18:16,867 OF PALE AREAS. 403 00:18:16,867 --> 00:18:20,137 THIS IS THE ANTRUM, MULTIPLE 404 00:18:20,137 --> 00:18:23,540 PALE AREAS, THIS IS THE BODY, 405 00:18:23,540 --> 00:18:27,911 YOU CAN SEE SOME NODULARITY, 406 00:18:27,911 --> 00:18:30,814 MORE PALE AREAS, THIS IS NARROW 407 00:18:30,814 --> 00:18:32,849 BAND IMAGING AND PARTICULARLY 408 00:18:32,849 --> 00:18:35,586 WE'RE DRAWN TO THIS AREA, MORE 409 00:18:35,586 --> 00:18:42,593 PALE AREAS AND WE BIOPSY THIS 410 00:18:42,593 --> 00:18:43,594 AREA. 411 00:18:43,594 --> 00:18:46,763 YOU CAN BE SYMPATHETIC TO THE 412 00:18:46,763 --> 00:18:49,433 PATHO LOGIST WHO HAD TO LOOK AT 413 00:18:49,433 --> 00:18:50,233 88 SPECIMENS. 414 00:18:50,233 --> 00:18:53,070 THESE ARE THE RESULTS PUBLISHED 415 00:18:53,070 --> 00:18:57,674 FROM THIS INSTITUTION BY THE 416 00:18:57,674 --> 00:18:59,176 GROUP ON THE 270 PATIENTS WHO 417 00:18:59,176 --> 00:19:06,049 HAVE BEEN SCREENED SINCE 2017 TO 418 00:19:06,049 --> 00:19:07,150 12/21 IN LANCET ONCOLOGY. 419 00:19:07,150 --> 00:19:10,287 YOU CAN SEE ABOUT 90 PERCENT OF 420 00:19:10,287 --> 00:19:13,790 THE CASES WERE BETHESDA. 421 00:19:13,790 --> 00:19:16,793 THERE WERE 467 PROCEDURES, ABOUT 422 00:19:16,793 --> 00:19:18,495 9 PERCENT WERE CAMBRIDGE. 423 00:19:18,495 --> 00:19:22,499 THE DETECTION RATE IS 424 00:19:22,499 --> 00:19:26,503 34 PERCENT, THAT IS 157 AND 157 425 00:19:26,503 --> 00:19:29,106 OF 467 RANDOM BIOPSIES WERE 426 00:19:29,106 --> 00:19:29,673 POSITIVE. 427 00:19:29,673 --> 00:19:30,540 TARGETED ALONE, LESS THAN 428 00:19:30,540 --> 00:19:30,907 1 PERCENT. 429 00:19:30,907 --> 00:19:34,878 SO WE WERE NOT VERY GOOD AT 430 00:19:34,878 --> 00:19:36,079 IDENTIFYING AN ABNORMALITY THAT 431 00:19:36,079 --> 00:19:38,415 HAD CANCER IN IT AND THAT 432 00:19:38,415 --> 00:19:41,385 NUMBER, IF YOU HAD BOTH TARGETED 433 00:19:41,385 --> 00:19:46,289 AND RANDOM POSITIVES, THAT WAS 434 00:19:46,289 --> 00:19:47,124 ALSO VERY SKEWED. 435 00:19:47,124 --> 00:19:55,298 SO WE CAN DETECT ABOUT 436 00:19:55,298 --> 00:19:55,599 34 PERCENT. 437 00:19:55,599 --> 00:19:59,036 YES, SO I WILL CLARIFY THAT 438 00:19:59,036 --> 00:20:01,104 THESE WERE SIGNET RING CELL 439 00:20:01,104 --> 00:20:02,572 POSITIVE BIOPSIES AND AGAIN, 440 00:20:02,572 --> 00:20:04,474 Dr. KIM WILL SHOW YOU WHAT 441 00:20:04,474 --> 00:20:07,911 THAT LOOKS LIKE, BUT THESE 442 00:20:07,911 --> 00:20:12,382 BIOPSIES ARE INTENDED TO DETECT 443 00:20:12,382 --> 00:20:17,954 THE SUBMUCOSAL LEAGUES LESION OR 444 00:20:17,954 --> 00:20:20,190 THOSE THAT ARE MORE INVASIVE. 445 00:20:20,190 --> 00:20:24,661 YOU ALSO CAN SEE THESE 446 00:20:24,661 --> 00:20:28,031 SURVEILLANCE NUMBERS THAT ARE 447 00:20:28,031 --> 00:20:31,435 DECREASING OVER TIME AND THE 448 00:20:31,435 --> 00:20:36,073 SIGNET CELLS THAT WERE POSITIVE 449 00:20:36,073 --> 00:20:40,477 WERE 270 SO AGAIN WE WOULD 450 00:20:40,477 --> 00:20:44,381 IDENTIFY 35 TO 40 PERCENT AND IN 451 00:20:44,381 --> 00:20:46,783 TWO PATIENTS, THAT NUMBER IS 452 00:20:46,783 --> 00:20:50,787 PROBABLY NOT VERY COULD IT. 453 00:20:50,787 --> 00:20:52,155 ACCURATE. 454 00:20:52,155 --> 00:20:56,660 THIS IS NOW UPDATED AND THIS 455 00:20:56,660 --> 00:21:00,097 WORK IS CURRENTLY UNPUBLISHED, 456 00:21:00,097 --> 00:21:05,035 REEF RANDOM BIOPSIES OF SIGNET 457 00:21:05,035 --> 00:21:06,870 RING CELLS IN 28 PORTION OF THE 458 00:21:06,870 --> 00:21:07,571 CASES. 459 00:21:07,571 --> 00:21:13,477 WE ARE UP NOW TO 744 BIOPSIES. 460 00:21:13,477 --> 00:21:15,078 IN TARGETING WHERE WE THOUGHT 461 00:21:15,078 --> 00:21:18,048 THERE WAS AN ABNORMALITY, ONLY 462 00:21:18,048 --> 00:21:18,582 12 OF 744. 463 00:21:18,582 --> 00:21:20,083 IF THEY WERE RANDOM AND 464 00:21:20,083 --> 00:21:21,952 TARGETED, MEANING BOTH WERE 465 00:21:21,952 --> 00:21:23,754 POSITIVE, THAT WAS ABOUT 466 00:21:23,754 --> 00:21:26,389 3.6 PERCENT AND WE FOCUSED 467 00:21:26,389 --> 00:21:28,358 PARTICULARLY ON THE BIOPSYING OF 468 00:21:28,358 --> 00:21:30,127 PALE AREAS AND WHAT THE YIELD 469 00:21:30,127 --> 00:21:32,028 WAS AND IT WAS ACTUALLY NOT VERY 470 00:21:32,028 --> 00:21:32,796 GOOD. 471 00:21:32,796 --> 00:21:36,133 SO OF THE 149 PALE AREAS WE 472 00:21:36,133 --> 00:21:39,269 IDENTIFIED, ONLY 21 WERE 473 00:21:39,269 --> 00:21:41,138 ACTUALLY POSITIVE. 474 00:21:41,138 --> 00:21:42,939 NOW, HERE AGAIN, WE CONTINUE 475 00:21:42,939 --> 00:21:44,574 WITH SURVEILLANCE AND NOW WE'RE 476 00:21:44,574 --> 00:21:48,078 UP TO A MEDIAN OF ABOUT 46 477 00:21:48,078 --> 00:21:50,347 MONTHS OF PATIENTS WHO ARE BEING 478 00:21:50,347 --> 00:21:53,683 MONITORED AND YOU CAN SEE THAT 479 00:21:53,683 --> 00:21:57,154 THE DETECTION RATE FOR SIGNET 480 00:21:57,154 --> 00:22:00,390 RING CELLS WITH PATIENTS AT RISK 481 00:22:00,390 --> 00:22:03,860 DECLINING, IT REMAINS AT 482 00:22:03,860 --> 00:22:05,762 APPROXIMATELY 35 PERCENT. 483 00:22:05,762 --> 00:22:11,034 SO WHAT'S THE ROLE OF THE 484 00:22:11,034 --> 00:22:13,036 ENDOSCOPY IN GASTRIC CANCER 485 00:22:13,036 --> 00:22:15,672 DETECTION AND SURVEILLANCE? 486 00:22:15,672 --> 00:22:19,409 SO ENDOSCOPY MAY BE THE 487 00:22:19,409 --> 00:22:23,246 ALTERNATIVE TO REDUCING 488 00:22:23,246 --> 00:22:31,721 GASITRECTOMY AND TODAY IN THIS 489 00:22:31,721 --> 00:22:35,492 POPULATION, NO ADVANCED GASTRIC 490 00:22:35,492 --> 00:22:37,427 CANCERS WERE IDENTIFIED BUT THE 491 00:22:37,427 --> 00:22:44,901 RISK REMAINS UNKNOWN. 492 00:22:44,901 --> 00:22:46,837 THE ENDOSCOPIC SURVEILLANCE IS 493 00:22:46,837 --> 00:22:52,142 UNKNOWN, HAS NOT BEEN DEFINED, 494 00:22:52,142 --> 00:23:01,017 THE APPEARANCES OF 495 00:23:01,017 --> 00:23:03,019 ADVANCEDLESIONS ARE POORLY 496 00:23:03,019 --> 00:23:03,653 DEFINED. 497 00:23:03,653 --> 00:23:07,290 THE OPTIMAL EXAMINATION METHODS 498 00:23:07,290 --> 00:23:09,726 FOR ENDOSCOPIC EXAMINATION ARE 499 00:23:09,726 --> 00:23:12,028 NOT STANDARDIZED, WE HAVE RANDOM 500 00:23:12,028 --> 00:23:14,698 BIOPSIES VERSUS THE TARGETING, 501 00:23:14,698 --> 00:23:19,803 END THEY ARE OBSERVER VARIATION 502 00:23:19,803 --> 00:23:23,573 AND ENDOSCOPIC TECHNOLOGY OR 503 00:23:23,573 --> 00:23:24,674 MAGNIFICATION AND CONFOCAL 504 00:23:24,674 --> 00:23:25,308 IMAGING AS WELL. 505 00:23:25,308 --> 00:23:28,778 SO WITH THAT I WOULD LIKE TO 506 00:23:28,778 --> 00:23:31,047 TURN IT OVER TO THE DOCTOR WHO 507 00:23:31,047 --> 00:23:32,782 TREATED THESE CASES. 508 00:23:32,782 --> 00:23:33,049 THANK YOU. 509 00:23:33,049 --> 00:23:36,686 >> THANK YOU, Dr. KORMAN FOR 510 00:23:36,686 --> 00:23:37,487 THE INTRODUCTION. 511 00:23:37,487 --> 00:23:41,491 HI, MY NAME IS SUN A KIM FROM 512 00:23:41,491 --> 00:23:43,360 PATHOLOGY AND TODAY I WOULD LIKE 513 00:23:43,360 --> 00:23:48,932 TO PRESENT THE PATHOLOGY OF THE 514 00:23:48,932 --> 00:23:50,667 SIGNET GASTRIC CANCER MASS ON 515 00:23:50,667 --> 00:23:53,837 THIS BOY AND ALSO ANOTHER CASE, 516 00:23:53,837 --> 00:23:58,575 A 34-YEAR-OLD FEMALE WHO HAD A 517 00:23:58,575 --> 00:24:03,313 GASTRECTOMY AND I CAN SHOW THAT 518 00:24:03,313 --> 00:24:03,546 ALSO. 519 00:24:03,546 --> 00:24:08,184 ALL RIGHT, SO WE THINK THE 520 00:24:08,184 --> 00:24:11,655 GASTRIC BY CROPS SEE, WE HAVE 521 00:24:11,655 --> 00:24:13,556 THE SIG NET RING CELL IN THIS 522 00:24:13,556 --> 00:24:16,760 AREA, WE CAN SEE THIS IN THE 523 00:24:16,760 --> 00:24:26,870 LINING OF THE PROPIA FLOATING 524 00:24:26,870 --> 00:24:30,206 AWAY TOWARDS THE EPITHELIUM. 525 00:24:30,206 --> 00:24:33,643 AND THE CELLS ARE REPLACING AND 526 00:24:33,643 --> 00:24:35,378 DECREASING THE NUCLEI OF THE 527 00:24:35,378 --> 00:24:38,281 CELLS GIVING THE APPEARANCE OF 528 00:24:38,281 --> 00:24:42,852 SIGNET RINGS. 529 00:24:42,852 --> 00:24:49,993 AND THIS IS THE FIRST BIOPSY IN 530 00:24:49,993 --> 00:24:52,095 2023, THE SIZE 1MM AND THE 531 00:24:52,095 --> 00:24:53,596 STAINING IS A LITTLE DIFFERENT, 532 00:24:53,596 --> 00:24:55,699 THE COLOR IS A LITTLE DIFFERENT 533 00:24:55,699 --> 00:24:58,201 BECAUSE IT WAS DONE BY OUTSIDE 534 00:24:58,201 --> 00:25:04,140 HOSPITAL BUT WE HAVE SPECIFIC 535 00:25:04,140 --> 00:25:12,415 SIGNET RING CELLS IN THE PROPRIA 536 00:25:12,415 --> 00:25:14,918 WITH CYTOPLASMA AND AS YOU LOOK 537 00:25:14,918 --> 00:25:17,954 IN THIS WAY, THE CELLS ARE A 538 00:25:17,954 --> 00:25:22,225 LITTLE HIGHER THE CELLS LOOK 539 00:25:22,225 --> 00:25:23,026 DIFFERENT. 540 00:25:23,026 --> 00:25:30,300 AND THE CELLS IN THIS BORDER HAS 541 00:25:30,300 --> 00:25:34,137 MOVED CYTOPLASMA SO THE SIZE IS 542 00:25:34,137 --> 00:25:38,141 SMALLER AND LESS GAS USING THE 543 00:25:38,141 --> 00:25:38,575 EPITHELIAL. 544 00:25:38,575 --> 00:25:45,849 AND INTERESTING THAT THE SIGNET 545 00:25:45,849 --> 00:25:49,152 RING CELLS INVADING DEEP IN 546 00:25:49,152 --> 00:25:49,686 THE -- 547 00:25:49,686 --> 00:25:50,186 [INDISCERNIBLE] 548 00:25:50,186 --> 00:25:55,392 SO YOU HAVE THE RING CELL 549 00:25:55,392 --> 00:25:57,594 FEATURE WITH PPMI BUT A 550 00:25:57,594 --> 00:26:01,664 DIFFERENT TYPE OF THE SIGNET 551 00:26:01,664 --> 00:26:01,865 RING. 552 00:26:01,865 --> 00:26:12,342 SO WE HAVE THE CANCER CELLS 553 00:26:17,180 --> 00:26:18,348 HERE. 554 00:26:18,348 --> 00:26:22,085 THE ECADHERIN CAME FROM THE 555 00:26:22,085 --> 00:26:24,454 EPITHELIUM SO THE PICTURE ON THE 556 00:26:24,454 --> 00:26:34,998 RIGHT SIDE, THE CYTOKERATIN FOR 557 00:26:35,198 --> 00:26:37,634 THE CMH1 GENE AND THE MEMBRANE, 558 00:26:37,634 --> 00:26:40,937 YOU CAN SEE THIS BROWN STAINING 559 00:26:40,937 --> 00:26:44,741 IN THE EXTERIOR MEMBRANE BUT IN 560 00:26:44,741 --> 00:26:48,378 THE SIGNET RING, WE SEE LIGHT 561 00:26:48,378 --> 00:26:50,647 BROWN STAINING IN THE CYTOPLASM, 562 00:26:50,647 --> 00:26:58,054 NOT IN THE MEMBRANE SO IT LOSES 563 00:26:58,054 --> 00:27:04,494 THE MEMBRANE EXPRESSION. 564 00:27:04,494 --> 00:27:08,164 THE MOLECULE, MOSTLY COHESIVE 565 00:27:08,164 --> 00:27:09,299 AND SINGULARLY ADHESIVE INSTEAD 566 00:27:09,299 --> 00:27:10,767 OF MAKING ANY OTHER STRUCTURES. 567 00:27:10,767 --> 00:27:18,608 SO THIS IS THE BIOPSY, THE BODY 568 00:27:18,608 --> 00:27:23,379 BIOPSY, VERY SMALL FOCUS, 569 00:27:23,379 --> 00:27:27,517 BIOPSIES OF FUNDAMENTAL CANCER 570 00:27:27,517 --> 00:27:30,019 FROM THE ANTRUM AND THIS IS THE 571 00:27:30,019 --> 00:27:34,290 ACTIVE SHIFT STAIN THAT 572 00:27:34,290 --> 00:27:37,460 HIGHLIGHTS THE SIGNET RING CELL 573 00:27:37,460 --> 00:27:42,332 AS WELL AS THE NEO PLASTIC 574 00:27:42,332 --> 00:27:44,701 EPITHELIUM AND BECAUSE THESE ARE 575 00:27:44,701 --> 00:27:45,869 VERY PATIENT DEPENDING ON THE 576 00:27:45,869 --> 00:27:47,537 PATIENT, WE USE THESE STAINS TO 577 00:27:47,537 --> 00:27:51,074 MORE EASILY SPOT THE CANCER 578 00:27:51,074 --> 00:27:52,876 FIRST TIME. 579 00:27:52,876 --> 00:27:57,080 IN THIS PICTURE, THERE ARE 580 00:27:57,080 --> 00:28:00,483 BACKGROUND SIGNET CELL IN THE 581 00:28:00,483 --> 00:28:02,986 BACKGROUND OF THE PROPIA BUT IF 582 00:28:02,986 --> 00:28:04,721 YOU LOOK HERE, WE HAVE THE CELLS 583 00:28:04,721 --> 00:28:13,930 IN THE GLAND LAR STRUCTURE AND 584 00:28:13,930 --> 00:28:15,598 THEY HAVE THE STRUCTURE WITH YOU 585 00:28:15,598 --> 00:28:16,866 THEY ARE RETAINED WITHIN THE 586 00:28:16,866 --> 00:28:22,539 BLAND SO THIS IS WHAT WE CALL 587 00:28:22,539 --> 00:28:24,140 SIGNET CELL CARCINOMA INSIDE. 588 00:28:24,140 --> 00:28:28,144 SO I WOULD LIKE TO PRESENT THIS 589 00:28:28,144 --> 00:28:30,647 CASE OF THE 34-YEAR-OLD FEMALE 590 00:28:30,647 --> 00:28:33,683 WHO CAME TO US AS PATIENT 591 00:28:33,683 --> 00:28:36,819 BECAUSE GASTRIC ISSUES WERE VERY 592 00:28:36,819 --> 00:28:43,726 TYPICAL TO THE SIGNET CELL 593 00:28:43,726 --> 00:28:44,494 CARCINOMA. 594 00:28:44,494 --> 00:28:46,262 SO MULTIPLE BIOPSIES FROM 595 00:28:46,262 --> 00:28:49,399 DIFFERENT AREAS SHOWS SIGNET 596 00:28:49,399 --> 00:28:51,067 CELL CARCINOMA. 597 00:28:51,067 --> 00:28:52,769 THE SIZES WERE SMALLER AND 598 00:28:52,769 --> 00:28:59,309 TYPICALLY WE HAVE THIS SIGNET 599 00:28:59,309 --> 00:29:02,245 CELL INFILTRATION IN THE MUCOSA 600 00:29:02,245 --> 00:29:05,248 AND YOU CAN SEE THE INFILTRATION 601 00:29:05,248 --> 00:29:07,951 IS MORE SMALLER COMPARED T THE 602 00:29:07,951 --> 00:29:18,461 CELLS IN WHICH WE HAD VOLUME. 603 00:29:22,298 --> 00:29:23,900 THIS SHOWS SIGNET CELLS FROM 604 00:29:23,900 --> 00:29:24,667 MULTIPLE AREAS. 605 00:29:24,667 --> 00:29:30,707 THIS IS FROM HER GASTRIC 606 00:29:30,707 --> 00:29:36,112 SPECIMEN, THE TOP PART, AND THEN 607 00:29:36,112 --> 00:29:42,352 THE BOTTOM PART WITH CARCINOMA. 608 00:29:42,352 --> 00:29:44,520 AND THE EPITHELIUM IS LARGE R 609 00:29:44,520 --> 00:29:49,492 AND THERE ARE TWO AREAS SO UPPER 610 00:29:49,492 --> 00:29:54,797 LAYER WE SEE THESE CELLS. 611 00:29:54,797 --> 00:30:01,638 THE LOWER LAYER WITH MORE -- 612 00:30:01,638 --> 00:30:02,905 [INDISCERNIBLE] 613 00:30:02,905 --> 00:30:03,573 CELLS. 614 00:30:03,573 --> 00:30:12,248 AND THIS HIGHLIGHT THE AREAS, 615 00:30:12,248 --> 00:30:13,149 TYPICALLY DISTRIBUTED ALONG THE 616 00:30:13,149 --> 00:30:20,723 MUSIC KOES IS A AND ALONG THE 617 00:30:20,723 --> 00:30:22,425 EPITHELIUM SURFACE. 618 00:30:22,425 --> 00:30:25,228 THEY DON'T MAKE MASS AND SO THIS 619 00:30:25,228 --> 00:30:31,200 EXPLAINS WHY THE SIGNET CELL 620 00:30:31,200 --> 00:30:35,271 SHOWS NO ABNORMAL APPEARANCE IN 621 00:30:35,271 --> 00:30:38,308 THE ENDOSCOPY. 622 00:30:38,308 --> 00:30:44,080 THERE ARE 94, LARGEST 16M BUT 623 00:30:44,080 --> 00:30:49,552 THE SMALLER SIZE LESS THAN 1M 624 00:30:49,552 --> 00:30:51,354 OVER THE STOMACH. 625 00:30:51,354 --> 00:30:59,962 EVEN THESE LARGER NUMBERS, IN 626 00:30:59,962 --> 00:31:02,665 THIS CASE SO THIS IS THE 627 00:31:02,665 --> 00:31:08,237 PATHOLOGY AND NOW I DIRECT YOU 628 00:31:08,237 --> 00:31:11,708 TO GRACE-ANN FASAYE. 629 00:31:11,708 --> 00:31:15,978 >> THANK YOU, DOCTOR KIM AND 630 00:31:15,978 --> 00:31:16,846 GOOD AFTERNOON, EVERYONE. 631 00:31:16,846 --> 00:31:19,549 SO I AM GOING TO BE FOCUSING ON 632 00:31:19,549 --> 00:31:24,320 THE CASE OF THE 11-YEAR-OLD BOY. 633 00:31:24,320 --> 00:31:27,323 AND USING THAT TO HIGHLIGHT 634 00:31:27,323 --> 00:31:30,893 TESTING, INDICATIONS FOR CDH1 635 00:31:30,893 --> 00:31:35,765 AND DISCUSSING A PEN 636 00:31:35,765 --> 00:31:38,000 TRANSETRANCE STUDY OUR TEAM IS 637 00:31:38,000 --> 00:31:40,670 WORKING ON, SO PENETRANCE BEING 638 00:31:40,670 --> 00:31:43,539 THE RISK OF DEVELOPING CANCER 639 00:31:43,539 --> 00:31:47,343 BASED ON THE CDHM1 PATHOGEN. 640 00:31:47,343 --> 00:31:51,247 SO AS YOU KNOW, THE 11-YEAR-OLD 641 00:31:51,247 --> 00:31:54,584 HAD ADHD AND AUTISM SPECTRUM 642 00:31:54,584 --> 00:31:55,051 DISORDER. 643 00:31:55,051 --> 00:31:57,120 SO THE GENETIC WORKUP, THAT IS 644 00:31:57,120 --> 00:32:00,256 WHAT REALLY LED TO THE 645 00:32:00,256 --> 00:32:04,060 INCIDENTAL FINDING OF THE 646 00:32:04,060 --> 00:32:04,861 PATHOGENIC VARIANT AND I WILL 647 00:32:04,861 --> 00:32:11,234 DELL DELVE INTO THAT A LITTLE 648 00:32:11,234 --> 00:32:11,434 MORE. 649 00:32:11,434 --> 00:32:14,871 SPECIFICALLY WHEN IT COMES TO 650 00:32:14,871 --> 00:32:18,274 TESTING FOR CDH1 IT CAN BE BASED 651 00:32:18,274 --> 00:32:19,575 ON FAMILY FACTORS OR OTHER 652 00:32:19,575 --> 00:32:23,212 FACTORS AND WHEN IT COMES TO 653 00:32:23,212 --> 00:32:32,855 FAMILY CRITERIA, WE FOCUS ON THE 654 00:32:32,855 --> 00:32:34,824 GASTRIC CANCER FOCUS AND USUALLY 655 00:32:34,824 --> 00:32:39,929 IT IS A CASE OF LOBULAR BREAST 656 00:32:39,929 --> 00:32:42,999 CANCER AND ALSO IF THERE IS A 657 00:32:42,999 --> 00:32:46,636 BLOOD RELATIVE KNOWN WITH A CDH 658 00:32:46,636 --> 00:32:47,303 VARIANT. 659 00:32:47,303 --> 00:32:48,070 THE CANCER RISK IS NOT 660 00:32:48,070 --> 00:32:50,873 CONSIDERED HE WILL VANITY IN 661 00:32:50,873 --> 00:32:51,741 CHILDREN WITH CDH1. 662 00:32:51,741 --> 00:32:54,410 IT IS CONSIDERED ADULT ONSET 663 00:32:54,410 --> 00:32:56,779 CONDITION AND THERE IS NO 664 00:32:56,779 --> 00:32:59,248 MEDICAL MANAGEMENT IN CHILDREN. 665 00:32:59,248 --> 00:33:01,517 AND TESTING SHOULD WAIT TILL THE 666 00:33:01,517 --> 00:33:03,453 AGE OF CONSENT WHICH IS USUALLY 667 00:33:03,453 --> 00:33:05,688 18 BUT CAN BE EARLIER IF THERE 668 00:33:05,688 --> 00:33:07,356 ARE ONSET CANCERS IN THE FAMILY. 669 00:33:07,356 --> 00:33:15,498 SO THE QUESTION COMES AGAIN, HOW 670 00:33:15,498 --> 00:33:18,134 DOES THE CDH1 GET PICKED UP. 671 00:33:18,134 --> 00:33:23,606 SO THIS IS THE WORKUP AND THOSE 672 00:33:23,606 --> 00:33:26,242 OF YOU FAMILIAR WITH FAMILY 673 00:33:26,242 --> 00:33:28,444 TREES, THE CIRCLES REPRESENT 674 00:33:28,444 --> 00:33:32,014 MALES, THE SQUARES THE FEMALES 675 00:33:32,014 --> 00:33:40,223 AND THE ARROW POINTS TO THE 676 00:33:40,223 --> 00:33:40,456 FAMILY. 677 00:33:40,456 --> 00:33:43,292 YOU CAN SEE THERE IS HIGH 678 00:33:43,292 --> 00:33:45,595 CHOLESTEROL, MOM HAS A CLEFT 679 00:33:45,595 --> 00:33:48,564 PALATE AS WELL AS A MATERNAL 680 00:33:48,564 --> 00:33:50,867 COUSIN BUT NO KNOWN FAMILY 681 00:33:50,867 --> 00:33:52,969 HISTORY OF ANY CANCERS IN THE 682 00:33:52,969 --> 00:33:53,302 FAMILY. 683 00:33:53,302 --> 00:33:56,038 AS FAR AS INDIVIDUAL CRITERIA, 684 00:33:56,038 --> 00:33:57,240 AGAIN, IT FOCUSES -- BECAUSE 685 00:33:57,240 --> 00:33:59,075 FAMILIES CAN BE SMALL, SOME 686 00:33:59,075 --> 00:34:01,143 PEOPLE DON'T KNOW THEIR FAMILY 687 00:34:01,143 --> 00:34:02,678 HISTORY, SO CRITERIA HAS EVOLVED 688 00:34:02,678 --> 00:34:04,280 OVER THE YEARS TO FOCUS ON THE 689 00:34:04,280 --> 00:34:06,182 PATIENT IN FRONT OF AND YOU 690 00:34:06,182 --> 00:34:12,755 FEIGN TO -- AGAIN TO LOOK AT 691 00:34:12,755 --> 00:34:15,825 CDH1, IT CAN BE ANYONE WITH 692 00:34:15,825 --> 00:34:26,369 CANCER AT ANY AGE, CLEFT PALATE, 693 00:34:27,970 --> 00:34:28,871 MAORI ETHNICITY. 694 00:34:28,871 --> 00:34:31,574 SO THIS WAS LOOKED AT WITH A 695 00:34:31,574 --> 00:34:35,311 HIKE CROW ARRAY TO LOOK FOR 696 00:34:35,311 --> 00:34:39,415 DELETIONS AND DUPLICATIONS IN 697 00:34:39,415 --> 00:34:41,751 CHROMOSOMES WHICH CAN BE 698 00:34:41,751 --> 00:34:43,252 INDICATION OF DEVELOPMENT 699 00:34:43,252 --> 00:34:43,986 DISORDERS. 700 00:34:43,986 --> 00:34:48,858 THIS IS SUPPORTED BY THE COLLEGE 701 00:34:48,858 --> 00:34:53,362 OF PEDIATRICS AND GENOMICS, THEY 702 00:34:53,362 --> 00:34:55,932 REPRESENT THIS FOR AUTISM AND 703 00:34:55,932 --> 00:34:56,732 DEVELOPMENTAL DELAY. 704 00:34:56,732 --> 00:34:59,035 SO WHEN THIS TEST IS DONE, IN 705 00:34:59,035 --> 00:35:08,978 SOME CASES IT CAN PICK UP SOME 706 00:35:08,978 --> 00:35:12,715 INCIDENTAL FINDINGS BUT NO 707 00:35:12,715 --> 00:35:18,154 REASON TO SUSPECT CDH1 FOR 708 00:35:18,154 --> 00:35:18,387 CANCER. 709 00:35:18,387 --> 00:35:22,959 SO THERE IS ANOTHER CASE IN THE 710 00:35:22,959 --> 00:35:24,160 LITERATURE WITH SIMILAR GENETIC 711 00:35:24,160 --> 00:35:28,831 FINDING AS THIS CASE SO THAT IS 712 00:35:28,831 --> 00:35:30,333 WHAT THESE IMAGES WERE TAKEN 713 00:35:30,333 --> 00:35:30,533 FROM. 714 00:35:30,533 --> 00:35:33,402 SO ON THE LEFT THERE IS 715 00:35:33,402 --> 00:35:35,371 CHROMOSOME 16 WHERE CDH1 IS 716 00:35:35,371 --> 00:35:40,543 LOCATED AND THE BLUE BAR ON THE 717 00:35:40,543 --> 00:35:43,179 CHROMOSOME REPRESENTS A MICRODEL 718 00:35:43,179 --> 00:35:45,281 LEAGUES THAT WAS IDENTIFIED ON 719 00:35:45,281 --> 00:35:55,825 THE LONG ARM OF CHROMOSOME 16, A 720 00:35:56,025 --> 00:35:59,729 245KB DELETION AND THIS IS THE 721 00:35:59,729 --> 00:36:07,403 TWO EXONS FROM THE CDH1 GENE AND 722 00:36:07,403 --> 00:36:08,938 THEN THE CHROMOSOME 15 WHERE THE 723 00:36:08,938 --> 00:36:10,706 WHITE ARROW IS POINTING. 724 00:36:10,706 --> 00:36:17,079 SO BECAUSE THIS MIKE CREE 725 00:36:17,079 --> 00:36:19,048 >> Mike: CROW DEL LEAGUES WAS 726 00:36:19,048 --> 00:36:23,853 FOUND AND WE KNOW THERE IS ONE 727 00:36:23,853 --> 00:36:34,363 CDH1 GENE IN THE LOCATION, WE 728 00:36:36,232 --> 00:36:37,066 RECOMMENDED TESTING FOR 729 00:36:37,066 --> 00:36:39,869 RELATIVES AND FAMILY AT RISK AND 730 00:36:39,869 --> 00:36:41,771 THE TESTING STARTED WITH THE 731 00:36:41,771 --> 00:36:46,008 PATIENT'S MOTHER BECAUSE SHE HAD 732 00:36:46,008 --> 00:36:49,078 CLEFT LIP AND PALATE SO SHE 733 00:36:49,078 --> 00:36:51,313 SEEMED MORE LIKELY THAN THE 734 00:36:51,313 --> 00:36:54,016 FATHER AND SHE WAS THE ONE THAT 735 00:36:54,016 --> 00:36:55,951 TESTED POSITIVE. 736 00:36:55,951 --> 00:36:58,120 THE OLDER SISTER WAS TESTED, SHE 737 00:36:58,120 --> 00:36:59,121 WAS NEGATIVE. 738 00:36:59,121 --> 00:37:02,792 EVERYONE ELSE WAS POSITIVE 739 00:37:02,792 --> 00:37:04,360 INCLUDING MATERNAL UNCLE, AUNT, 740 00:37:04,360 --> 00:37:06,829 ALL OF THEIR CHILDREN AND 741 00:37:06,829 --> 00:37:07,697 MATERNAL GRANDMOTHER. 742 00:37:07,697 --> 00:37:11,300 ONE OF THE MATERNAL COUSINS WAS 743 00:37:11,300 --> 00:37:13,836 FOUND TO HAVE STAGE 1 GAS STRICK 744 00:37:13,836 --> 00:37:18,274 CANCER AND OPTED FOR A 745 00:37:18,274 --> 00:37:20,509 GASTRECTOMY AND A REPORT THERE 746 00:37:20,509 --> 00:37:23,846 WHAT THE TEST LOOKED LIKE FROM 747 00:37:23,846 --> 00:37:24,914 ONE OF THE RELATIVES. 748 00:37:24,914 --> 00:37:27,016 SO THAT FAMILY HISTORY WAS 749 00:37:27,016 --> 00:37:29,085 BEFORE THERE WAS ANY WORKUP AND 750 00:37:29,085 --> 00:37:31,620 WITH NO CANCER HISTORY, WOULD 751 00:37:31,620 --> 00:37:35,825 HAVE AN AN ANOMALY OF CDH120 752 00:37:35,825 --> 00:37:36,992 YEARS AGO BECAUSE THE RISKS 753 00:37:36,992 --> 00:37:39,328 PUBLISHED IN THE LITERATURE WERE 754 00:37:39,328 --> 00:37:41,964 AS HIGH AS 83 PERCENT FOR WOMEN 755 00:37:41,964 --> 00:37:43,566 AND 70 PERCENT FOR MEN. 756 00:37:43,566 --> 00:37:48,871 AND YOU SEE IN THOSE STUDIES IN 757 00:37:48,871 --> 00:37:52,374 2001 AND 2001 COMPARED WITH THE 758 00:37:52,374 --> 00:37:54,844 SEAR POPULATION IS SIGNIFICANTLY 759 00:37:54,844 --> 00:37:57,680 ELEVATED. 760 00:37:57,680 --> 00:38:00,783 THE EARLIER STUDIES WERE SMALL 761 00:38:00,783 --> 00:38:03,719 SAMPLE SIZES, FOUR IN ONE 762 00:38:03,719 --> 00:38:07,356 FAMILY, IN ANOTHER 11 AND 763 00:38:07,356 --> 00:38:08,591 DIFFUSE GASTRIC CANCER. 764 00:38:08,591 --> 00:38:12,228 THE 2015 IS STILL THE MOST 765 00:38:12,228 --> 00:38:15,431 CORRELATED STUDY, THEY FOUND 75 766 00:38:15,431 --> 00:38:19,735 BUT STILL THREE OR MORE PATIENTS 767 00:38:19,735 --> 00:38:21,270 WITH GASTRIC CANCER IN THAT 768 00:38:21,270 --> 00:38:22,204 FAMILY. 769 00:38:22,204 --> 00:38:24,140 THAT SHOWED A 70 PERCENT RISK 770 00:38:24,140 --> 00:38:27,343 AND THEN 56 PERCENT RISK FOR 771 00:38:27,343 --> 00:38:28,410 GASTRIC CANCER IN WOMEN. 772 00:38:28,410 --> 00:38:34,049 THE RISK FOR BREAST CANCER IN 773 00:38:34,049 --> 00:38:37,653 THESE PENETRANCE STUDIES HAVE 774 00:38:37,653 --> 00:38:39,922 BEEN PRETTY CONSISTENT FOR 775 00:38:39,922 --> 00:38:41,190 LOBULAR BREAST CANCER. 776 00:38:41,190 --> 00:38:44,627 WHEN IT COMES TO IMPLICATIONS 777 00:38:44,627 --> 00:38:46,595 FOR GENETIC TESTING, MANY WOMEN 778 00:38:46,595 --> 00:38:50,166 UNDERGO TESTING BECAUSE OF 779 00:38:50,166 --> 00:38:51,734 BREAST CANCER, DIAGNOSIS OR 780 00:38:51,734 --> 00:38:52,601 CLINICAL HISTORY. 781 00:38:52,601 --> 00:38:54,904 SO THE LARGE NUMBER OF LAPS THAT 782 00:38:54,904 --> 00:38:55,905 PERFORM THE TESTING, OFTEN THEY 783 00:38:55,905 --> 00:38:58,307 ARE DOING IT FOR THAT PARTICULAR 784 00:38:58,307 --> 00:38:58,774 INDICATION. 785 00:38:58,774 --> 00:39:02,511 SO TWO LAPS THAT OFFER CANCER 786 00:39:02,511 --> 00:39:03,646 GENETIC TESTING, SPECIFICALLY 787 00:39:03,646 --> 00:39:05,247 GENE PANEL TESTING WHERE THEY 788 00:39:05,247 --> 00:39:10,753 LOOK AT SEVERAL GENES, CDH1 AND 789 00:39:10,753 --> 00:39:13,455 THE MOST COMMON BREAST CANCER 790 00:39:13,455 --> 00:39:21,497 GENE, TWO OF THOSE LABS 791 00:39:21,497 --> 00:39:23,332 PUBLISHED THEIR CDH1, THERE WAS 792 00:39:23,332 --> 00:39:26,168 A BIOPSY BECAUSE THESE PEOPLE 793 00:39:26,168 --> 00:39:28,037 HAD CANCER OR FAMILY HISTORY BUT 794 00:39:28,037 --> 00:39:30,639 NOT THE STRONG GASTRIC FAMILY 795 00:39:30,639 --> 00:39:33,275 HISTORY AND THOSE STUDIES FOUND 796 00:39:33,275 --> 00:39:37,179 A MUCH LOWER LIST OF GASTRIC 797 00:39:37,179 --> 00:39:39,081 CANCER, 24 TO 42 PERCENT 798 00:39:39,081 --> 00:39:40,382 LIFETIME RISK. 799 00:39:40,382 --> 00:39:45,354 AND SO HERE AT NCI, OUR TEAM, WE 800 00:39:45,354 --> 00:39:48,958 ARE LEADING A PENETRANT STUDY 801 00:39:48,958 --> 00:39:50,226 BECAUSE WE HAVE A LARGE NUMBER 802 00:39:50,226 --> 00:39:53,195 OF FAMILIES, WE WANTED TO DO A 803 00:39:53,195 --> 00:39:55,164 MULTISITE STUDY AND SO WE HAD 804 00:39:55,164 --> 00:39:58,067 PARTNERED WITH THE CANCER AND 805 00:39:58,067 --> 00:40:01,337 GENETICS PROGRAM AS MASS 806 00:40:01,337 --> 00:40:03,305 GENERAL, STANFORD UNIVERSITY AND 807 00:40:03,305 --> 00:40:06,508 ALSO UNIVERSITY OF CHICAGO AND 808 00:40:06,508 --> 00:40:13,849 OUR STUDY HAD 213 FAMILIES WHO 809 00:40:13,849 --> 00:40:15,517 CONFIRMED CDH1 PATHOGE NIC 810 00:40:15,517 --> 00:40:15,885 VARIANT. 811 00:40:15,885 --> 00:40:19,455 NOW WE KNOW THAT SIGNET RING 812 00:40:19,455 --> 00:40:22,725 CELLS ARE COMMON IN INDIVIDUALS 813 00:40:22,725 --> 00:40:30,633 WITH CDH1 STAGE 1, WE REALLY DID 814 00:40:30,633 --> 00:40:38,507 FOCUS ON STAGE 2 TO 4 AND 815 00:40:38,507 --> 00:40:41,944 FOCUSED ON THOSE ANALYSIS FOR 816 00:40:41,944 --> 00:40:42,211 TREATMENT. 817 00:40:42,211 --> 00:40:44,747 SO THIS IS THE POPULATION, AN 818 00:40:44,747 --> 00:40:46,148 AVERAGE OF 30 INDIVIDUALS PER 819 00:40:46,148 --> 00:40:47,983 FAMILY AND AS FAR AS CANCER 820 00:40:47,983 --> 00:40:48,951 HISTORY, TOWARDS THE BOTTOM 821 00:40:48,951 --> 00:40:52,988 THERE WITH THE COMBINATION OF 822 00:40:52,988 --> 00:40:56,158 FAMILY, MOST HAD BREAST AND 823 00:40:56,158 --> 00:40:59,028 GASTRIC BUT WE SAW GASTRIC ONLY 824 00:40:59,028 --> 00:41:00,529 FAMILIES AND BREAST CANCER ONLY 825 00:41:00,529 --> 00:41:00,796 FAMILIES. 826 00:41:00,796 --> 00:41:04,466 AND AS FAR AS THE PENETRANCE 827 00:41:04,466 --> 00:41:05,868 ESTIMATES FROM OUR STUDY, 828 00:41:05,868 --> 00:41:08,270 THINKING BACK TO THE CASE OF THE 829 00:41:08,270 --> 00:41:12,107 11-YEAR-OLD, THE RISK TO DEVELOP 830 00:41:12,107 --> 00:41:14,043 GASTRIC CANCER, UP TO AGE 30 WAS 831 00:41:14,043 --> 00:41:16,578 A .2 PERCENT RISK. 832 00:41:16,578 --> 00:41:18,080 SO AGAIN, STAGE 2 TO 4 AND THAT 833 00:41:18,080 --> 00:41:23,018 IS THE SAME RISK FOR FEMALES. 834 00:41:23,018 --> 00:41:27,856 WE ALSO FOUND THAT LIFETIME UP 835 00:41:27,856 --> 00:41:30,559 RISK UP TO AGE 80, AROUND 836 00:41:30,559 --> 00:41:33,329 10 PERCENT FOR MALE AND 837 00:41:33,329 --> 00:41:34,196 6.5 PERCENT FOR FEMALES. 838 00:41:34,196 --> 00:41:35,764 SO THESE RISK ESTIMATES ARE 839 00:41:35,764 --> 00:41:38,000 SIGNIFICANTLY LOWER THAN THE 840 00:41:38,000 --> 00:41:39,368 INITIAL PUBLISHED ESTIMATES AND 841 00:41:39,368 --> 00:41:42,938 WHEN IT COMES TO, YOU KNOW, THE 842 00:41:42,938 --> 00:41:44,506 IMPLICATIONS FOR GENETIC 843 00:41:44,506 --> 00:41:46,375 COUNSELING FOR PATIENTS, WHAT IS 844 00:41:46,375 --> 00:41:48,277 IMPORTANT TO KEEP IN MIND WHEN 845 00:41:48,277 --> 00:41:52,815 TALKING TO PATIENTS, WE KNOW 846 00:41:52,815 --> 00:41:59,321 CDH1 IS ASSOCIATED WITH GAS TRIC 847 00:41:59,321 --> 00:42:00,956 CANCER RISK, MUCH HIGHER THAN 848 00:42:00,956 --> 00:42:02,391 THE GENERAL POPULATION. 849 00:42:02,391 --> 00:42:04,426 WE STILL DON'T UNDERSTAND WHY 850 00:42:04,426 --> 00:42:06,528 STAGE 1 PROGRESSES OR HOW FAST 851 00:42:06,528 --> 00:42:11,000 IT CAN PROGRESS AND BECAUSE OF 852 00:42:11,000 --> 00:42:14,069 THAT, A GASTRECTOMY IS A SAFE 853 00:42:14,069 --> 00:42:15,471 OPTION BUT ALSO SURVEILLANCE IS 854 00:42:15,471 --> 00:42:19,408 A SAFE OPTION AS WELL, LOOKING 855 00:42:19,408 --> 00:42:20,275 AT THERAPY, AND FAMILY HISTORY. 856 00:42:20,275 --> 00:42:22,244 IF THERE IS A STRONG FAMILY 857 00:42:22,244 --> 00:42:28,017 HISTORY OF GASTRIC CANCER, THEN 858 00:42:28,017 --> 00:42:32,755 PERHAPS THEIR RISK IS A LOT 859 00:42:32,755 --> 00:42:32,988 HIGHER. 860 00:42:32,988 --> 00:42:34,223 THANK YOU. 861 00:42:34,223 --> 00:42:34,923 >> THANKS, GRACE. 862 00:42:34,923 --> 00:42:38,727 I AM GOING TO TRY TO BRING 863 00:42:38,727 --> 00:42:39,528 EVERYTHING BACK TOGETHER. 864 00:42:39,528 --> 00:42:43,799 SO A COUPLE OF IMPORTANT THINGS 865 00:42:43,799 --> 00:42:46,168 THAT Dr. KORMAN SHOWED THAT 866 00:42:46,168 --> 00:42:47,536 HOPEFULLY CAME THROUGH, GOING 867 00:42:47,536 --> 00:42:48,303 BACK TO THE 11-YEAR-OLD. 868 00:42:48,303 --> 00:42:54,476 WHEN YOU HAVE A CDH1 FINDING, 869 00:42:54,476 --> 00:43:02,551 YOU DO AN ENDOSCOPY AND WHAT 870 00:43:02,551 --> 00:43:04,686 Dr. KORMAN SHOWED IS THE 871 00:43:04,686 --> 00:43:07,990 STOMACH LOOKS NORMAL, RIGHT? 872 00:43:07,990 --> 00:43:09,958 AND THAT IS A PROBLEM BECAUSE WE 873 00:43:09,958 --> 00:43:16,665 DON'T HAVE A WAY TO LOOK FOR 874 00:43:16,665 --> 00:43:18,200 G ASTRIC CANCER IN THESE PEOPLE 875 00:43:18,200 --> 00:43:19,902 IF THE STOMACH LOOKS NORMAL. 876 00:43:19,902 --> 00:43:21,937 BUT THEN WHAT Dr. KIM SHOWED 877 00:43:21,937 --> 00:43:27,676 YOU IS THIS KID HAD NOW TWO 878 00:43:27,676 --> 00:43:29,478 ENDOSCOPIES WITH RANDOM BIOPSIES 879 00:43:29,478 --> 00:43:32,514 SHOWING YOU THOSE LITTLE SIGNET 880 00:43:32,514 --> 00:43:35,918 CELLS IN TWO PARTS OF THE 881 00:43:35,918 --> 00:43:37,186 STOMACH AND WITH THE OTHER 882 00:43:37,186 --> 00:43:43,258 PATIENT, IT WOULD SHOW YOU 883 00:43:43,258 --> 00:43:47,229 94CIGNT RING CELLS WERE FOUND IN 884 00:43:47,229 --> 00:43:50,699 THAT PATIENT WHICH ARE PRETTY 885 00:43:50,699 --> 00:43:50,933 TYPICAL. 886 00:43:50,933 --> 00:43:56,705 SO NOW OFF YOU HAVE A KID WITH 887 00:43:56,705 --> 00:44:00,776 NO SPECIFIC HISTORY AND THESE 888 00:44:00,776 --> 00:44:03,112 SIGNET CELLS IN THE STOMACH. 889 00:44:03,112 --> 00:44:04,813 SO WHAT DO YOU DO? 890 00:44:04,813 --> 00:44:06,248 WHY DID HE EVEN END UP HERE? 891 00:44:06,248 --> 00:44:08,317 SO I WANT TO TELL YOU A LITTLE 892 00:44:08,317 --> 00:44:10,185 BIT OF THE STORY ABOUT HOW HE 893 00:44:10,185 --> 00:44:11,653 GOT HERE BECAUSE SOMEBODY MIGHT 894 00:44:11,653 --> 00:44:17,159 ASK HOW DID WE BECOME A CENTER 895 00:44:17,159 --> 00:44:19,595 OF EXPERTISE, WHICH WE ARE BY 896 00:44:19,595 --> 00:44:30,105 THE WAY, FOR REMEMBER RED -- 897 00:44:31,006 --> 00:44:39,181 HEREDITARY GASTRIC CANCER. 898 00:44:39,181 --> 00:44:40,482 WELL, GASDRIC CANCER IS RARE IN 899 00:44:40,482 --> 00:44:42,784 THE U.S. SO WHERE WILL YOU GET 900 00:44:42,784 --> 00:44:43,252 PATIENTS? 901 00:44:43,252 --> 00:44:45,988 AND DOES THE NIH HAVE THE 902 00:44:45,988 --> 00:44:47,890 EXPERTISE NECESSARY FOR PATIENTS 903 00:44:47,890 --> 00:44:50,526 AND THEN ANOTHER THING I HEARD 904 00:44:50,526 --> 00:44:54,062 WAS JEREMY, YOU ARE NOT A HIGH 905 00:44:54,062 --> 00:44:54,930 VOLUME GASTRIC SURGEON, IT IS 906 00:44:54,930 --> 00:44:56,932 NOT SAFE ANY WAY. 907 00:44:56,932 --> 00:45:05,040 SO MANY OF HE IS WHO CARE FOR 908 00:45:05,040 --> 00:45:08,610 GASTRIC CANCER AND CANCERS OF 909 00:45:08,610 --> 00:45:13,482 THE UPPER GI TRACT, WE KNOW THAT 910 00:45:13,482 --> 00:45:17,152 IT REQUIRES EXPERTISE IN CARING 911 00:45:17,152 --> 00:45:19,454 FOR THESE PATIENTS AND IS 912 00:45:19,454 --> 00:45:21,290 COORDINATED BY THESE GROUPS. 913 00:45:21,290 --> 00:45:24,059 AND SO WE FELT WE CAN'T BRING 914 00:45:24,059 --> 00:45:25,327 PATIENTS HERE IF WE CAN'T TAKE 915 00:45:25,327 --> 00:45:26,962 CARE OF THEM AND THIS IS 916 00:45:26,962 --> 00:45:28,730 PROBABLY THE FIRST MEETING OF 917 00:45:28,730 --> 00:45:30,199 THE TEAM BACK IN THE DAY AND I 918 00:45:30,199 --> 00:45:33,035 WOULD BALD BACK THEN TOO. 919 00:45:33,035 --> 00:45:36,905 SO IN 2017 WE OPENED THIS 920 00:45:36,905 --> 00:45:37,639 HEREDITARY GASTRIC CANCER 921 00:45:37,639 --> 00:45:39,841 PROTOCOL AND I WILL SHOW YOU 922 00:45:39,841 --> 00:45:41,276 THIS BECAUSE FRANKLY I WAS BLOWN 923 00:45:41,276 --> 00:45:42,811 AWAY BY IT AND I WANT TO SHOW 924 00:45:42,811 --> 00:45:43,478 YOU. 925 00:45:43,478 --> 00:45:45,714 THIS IS OUR ACCRUAL. 926 00:45:45,714 --> 00:45:46,848 IN 2017 WE OPENED AND YOU CAN 927 00:45:46,848 --> 00:45:50,519 SEE IN JUST A FEW YEARS, OUR 928 00:45:50,519 --> 00:45:51,787 CUMULATIVE ENROLLMENT JUST 929 00:45:51,787 --> 00:45:52,588 SKYROCKETED. 930 00:45:52,588 --> 00:45:54,957 AND TO THIS DATE, WE HAVE 931 00:45:54,957 --> 00:45:56,225 ENROLLED OVER 700 PEOPLE. 932 00:45:56,225 --> 00:45:58,093 NOW ON AVERAGE, IT IS ABOUT 7 933 00:45:58,093 --> 00:45:59,328 NEW PATIENTS PER MONTH. 934 00:45:59,328 --> 00:46:00,996 IT IS A NATURAL HISTORY STUDY. 935 00:46:00,996 --> 00:46:03,498 NOT ALL OF THEM PHYSICALLY COME 936 00:46:03,498 --> 00:46:06,702 HERE, BUT WE HAVE ABOUT 635 937 00:46:06,702 --> 00:46:08,337 PATIENTS CURRENTLY ON STUDY THAT 938 00:46:08,337 --> 00:46:11,173 COME FROM THROUGHOUT THE UNITED 939 00:46:11,173 --> 00:46:12,608 STATES, CANADA, MEXICO, AS A LOT 940 00:46:12,608 --> 00:46:14,743 OF STUDIES AROUND HERE DO. 941 00:46:14,743 --> 00:46:16,144 WE NOW HAVE 300 FAMILIES AND 942 00:46:16,144 --> 00:46:21,750 ABOUT 3/4 OF THEM HAVE 943 00:46:21,750 --> 00:46:24,653 PATHOGENIC OR LIKELY PATHOGENIC 944 00:46:24,653 --> 00:46:26,855 IN THE CDH1. 945 00:46:26,855 --> 00:46:31,627 SOME OF THEM HAVE OTHER 946 00:46:31,627 --> 00:46:35,163 SYNDROMES, CNA, ET CETERA. 947 00:46:35,163 --> 00:46:38,634 SO I WASN'T THE HIGH GASITRIC 948 00:46:38,634 --> 00:46:42,871 VOLUME SURGEON THEN BUT I AM NOW 949 00:46:42,871 --> 00:46:46,942 AND Dr. KORMAN AND HIS TEAM DO 950 00:46:46,942 --> 00:46:50,045 ABOUT 200 SURVEILLANCE 951 00:46:50,045 --> 00:46:56,551 ENDOSCOPIES JUST FOR CDH1 952 00:46:56,551 --> 00:46:57,886 ANNUALLY AND THEN WHAT I ALSO 953 00:46:57,886 --> 00:46:59,821 TOLD YOU WAS THE RECOMMENDATION 954 00:46:59,821 --> 00:47:01,923 THAT THESE PEOPLE JUST GET THEIR 955 00:47:01,923 --> 00:47:03,225 STOMACHS REMOVED. 956 00:47:03,225 --> 00:47:05,794 SO WE'RE NOT JUST TAKING OUT 957 00:47:05,794 --> 00:47:07,262 STOMACHS, WE'RE TRYING TO SAVE 958 00:47:07,262 --> 00:47:07,696 THEM AS WELL. 959 00:47:07,696 --> 00:47:09,598 AND THE STRENGTH OF OUR RESEARCH 960 00:47:09,598 --> 00:47:11,967 PROGRAM IS WE ARE THE ONLY ONE 961 00:47:11,967 --> 00:47:13,001 OF IT KIND IN THE U.S. 962 00:47:13,001 --> 00:47:15,570 I HAVE BEEN TO SLOAN KETTERING 963 00:47:15,570 --> 00:47:17,406 AND MD ANDERSON AND THEY CAN'T 964 00:47:17,406 --> 00:47:20,409 DO WHAT WE DO HERE. 965 00:47:20,409 --> 00:47:22,044 OBVIOUSLY WE PROVIDE OUTSTANDING 966 00:47:22,044 --> 00:47:23,578 CLINICAL CARE AND I WILL SHOW 967 00:47:23,578 --> 00:47:24,212 YOU THE RESEARCH. 968 00:47:24,212 --> 00:47:26,548 SO A COUPLE OF KEY TAKEAWAYS 969 00:47:26,548 --> 00:47:29,618 FROM WHAT YOU HAVE SEEN FROM 970 00:47:29,618 --> 00:47:31,887 Dr. KORMAN, Dr. KIM AND 971 00:47:31,887 --> 00:47:35,991 GRACE MENTIONED IT AS WELL, 972 00:47:35,991 --> 00:47:41,229 THESE SIGNET RING CELL LESIONS 973 00:47:41,229 --> 00:47:42,397 ARE UBIQUITOUS WITH PEOPLE 974 00:47:42,397 --> 00:47:46,501 WALKING AROUND WITH THIS CDH1 975 00:47:46,501 --> 00:47:46,902 GERMLINE VARIANTS. 976 00:47:46,902 --> 00:47:50,906 SO TO PROVE THAT, WE LOOKED AT 977 00:47:50,906 --> 00:47:53,775 PEOPLE WITH CDH1 MUTATION, THEY 978 00:47:53,775 --> 00:47:56,645 LOOK FINE, THEIR STOMACHS LOOK 979 00:47:56,645 --> 00:47:59,081 NORMAL BUT THEY SAY DOC I WANT 980 00:47:59,081 --> 00:47:59,981 MY STOMACH OUT BECAUSE I DON'T 981 00:47:59,981 --> 00:48:02,684 WANT TO GET STOMACH CANCER. 982 00:48:02,684 --> 00:48:07,556 SO WE LOOKED AT 150 OF THESE, 983 00:48:07,556 --> 00:48:09,825 Dr. GALONIS DID THIS, FROM 18 984 00:48:09,825 --> 00:48:11,393 AND THE OLDEST PERSON I HAVE 985 00:48:11,393 --> 00:48:13,095 DONE IS 80 YEARS OLD AND GUESS 986 00:48:13,095 --> 00:48:13,662 WHAT? 987 00:48:13,662 --> 00:48:16,732 88PERCENT OF THOSE CASES, Dr. 988 00:48:16,732 --> 00:48:24,506 KIM OR Dr. FASAYE FOUND 989 00:48:24,506 --> 00:48:26,241 MULTIFOCAL STAGE 1SIGNET RING 990 00:48:26,241 --> 00:48:32,714 CELL CARCINOMA WHICH WE SHOWED 991 00:48:32,714 --> 00:48:33,882 YOU IN THOSE SAMPLES. 992 00:48:33,882 --> 00:48:37,285 THE OTHER CASES WE LOOKED AT, WE 993 00:48:37,285 --> 00:48:40,689 COULDN'T FIND CANCER BUT I THINK 994 00:48:40,689 --> 00:48:42,224 THESE ARE FALSE NEGATIVES. 995 00:48:42,224 --> 00:48:44,826 YOU CAN'T LOOK AT THE ENTIRE 996 00:48:44,826 --> 00:48:46,395 STOMACH, WE WOULD BE DOING IT 997 00:48:46,395 --> 00:48:48,864 FOR DAYS ON END AND THAT WOULD 998 00:48:48,864 --> 00:48:50,732 PROBABLY KILL ME. 999 00:48:50,732 --> 00:48:59,541 SO THE TAKEAWAY, 93 PERCENT OF 1000 00:48:59,541 --> 00:49:01,076 THESE ASYMPTOMATIC GROUP HAVE 1001 00:49:01,076 --> 00:49:02,511 OCCULT CANCERS. 1002 00:49:02,511 --> 00:49:04,813 THE OTHER THING IS IT IS I.R.S. 1003 00:49:04,813 --> 00:49:06,782 RESPECTIVE OF THEIR FAMILY 1004 00:49:06,782 --> 00:49:07,149 HISTORY. 1005 00:49:07,149 --> 00:49:09,484 GRACE SHOWED YOU THE HISTORY OF 1006 00:49:09,484 --> 00:49:10,252 THE 11-YEAR-OLD. 1007 00:49:10,252 --> 00:49:13,889 THERE WAS NO CANCER IN HIS 1008 00:49:13,889 --> 00:49:14,122 FAMILY. 1009 00:49:14,122 --> 00:49:16,925 SO THEN GRACE CAME TO ME AND THE 1010 00:49:16,925 --> 00:49:20,796 LAB AND SAID LET'S LOOK AT 1011 00:49:20,796 --> 00:49:23,532 BREAST CANCER, NO STOMACH CANCER 1012 00:49:23,532 --> 00:49:26,735 BUT HAVE THE CDH1 VARIANT. 1013 00:49:26,735 --> 00:49:30,272 15 PILL DECIDED I WILL HAVE MY 1014 00:49:30,272 --> 00:49:32,507 STOMACH OUT ANY WAY. 1015 00:49:32,507 --> 00:49:39,481 94PERCENT HAD EARLY STAGE 1016 00:49:39,481 --> 00:49:42,884 MULTITOKE CALL SIGNET STAGE 1 1017 00:49:42,884 --> 00:49:43,585 CELL LESIONS. 1018 00:49:43,585 --> 00:49:46,855 SO THERE IS SOMETHING ABOUT CDH1 1019 00:49:46,855 --> 00:49:48,857 LOSS OF FUNCTION MUTATION OR 1020 00:49:48,857 --> 00:49:52,661 MAYBE LOSS OF EXPRESSION IN 1021 00:49:52,661 --> 00:49:53,995 EPITHELIAL PRECURSORS IN THE 1022 00:49:53,995 --> 00:49:57,933 STOMACH THAT LEAD TO THE SIGNET 1023 00:49:57,933 --> 00:49:59,935 RING CELLS IRRESPECTIVE OF 1024 00:49:59,935 --> 00:50:00,469 FAMILY HISTORY. 1025 00:50:00,469 --> 00:50:02,070 IT IS IMPORTANT TO KNOW IF YOU 1026 00:50:02,070 --> 00:50:04,639 DON'T HAVE A CDH1 MUTATION, WE 1027 00:50:04,639 --> 00:50:07,976 WOULD NOT EXPECT TO FIND THESE 1028 00:50:07,976 --> 00:50:11,713 SIGNET RING CELLS IN YOUR 1029 00:50:11,713 --> 00:50:12,047 STOMACH. 1030 00:50:12,047 --> 00:50:14,349 Dr. KORMAN FOUND A PAPER FROM 1031 00:50:14,349 --> 00:50:17,953 TEXAS LOOKING AT 300 ENDOSCOPIES 1032 00:50:17,953 --> 00:50:21,456 AND YOU JUST DON'T FIND THOSE 1033 00:50:21,456 --> 00:50:22,757 CELLS IN PEOPLE WITHOUT THE 1034 00:50:22,757 --> 00:50:23,225 MUTATION. 1035 00:50:23,225 --> 00:50:26,428 I AM A SURGEON, I TAKE OUT A LOT 1036 00:50:26,428 --> 00:50:29,197 OF STOMACHS. 1037 00:50:29,197 --> 00:50:33,068 SEAHORSES DON'T HAVE STOMACHS, 1038 00:50:33,068 --> 00:50:34,636 BY THE WAY. 1039 00:50:34,636 --> 00:50:38,273 THE NEXT PEOPLE GOT ZEBRAS, WE 1040 00:50:38,273 --> 00:50:38,940 GET THE SEAHORSES. 1041 00:50:38,940 --> 00:50:40,976 SO WHAT IS THE LOSS OF REMOVING 1042 00:50:40,976 --> 00:50:42,010 THE STOMACH? 1043 00:50:42,010 --> 00:50:43,979 PEOPLE MAY SAY WELL YOU ARE 1044 00:50:43,979 --> 00:50:48,250 REMOVING THE STOMACH, THAT IS 1045 00:50:48,250 --> 00:50:48,850 GREAT. 1046 00:50:48,850 --> 00:50:49,918 THAT IS ANOTHER DOCTOR 1047 00:50:49,918 --> 00:50:50,185 OPERATING. 1048 00:50:50,185 --> 00:50:53,588 I AM THE ONE WITH THE BAD BACK. 1049 00:50:53,588 --> 00:50:57,726 SHE LOOKED AT 126 PEOPLE WE DID 1050 00:50:57,726 --> 00:51:01,663 A GASTRECTOMY ON AND THE ACUTE 1051 00:51:01,663 --> 00:51:02,931 MAJOR MORBIDITY IS 6 PERCENT AND 1052 00:51:02,931 --> 00:51:04,599 I WOULD ARGUE THAT IS PROBABLY 1053 00:51:04,599 --> 00:51:07,769 IN LINE WITH OTHER CANCER 1054 00:51:07,769 --> 00:51:12,674 THERAPIES BE IT COMBINED WITH 1055 00:51:12,674 --> 00:51:14,609 CHEMOTHERAPY OR RADIATION, ET 1056 00:51:14,609 --> 00:51:14,843 CETERA. 1057 00:51:14,843 --> 00:51:20,048 BUT WHAT Dr. GALONES LOOKED AT 1058 00:51:20,048 --> 00:51:24,519 AND WHAT WE PUBLISHED, WHEN YOU 1059 00:51:24,519 --> 00:51:28,189 LOOK AT PEOPLE WITH 24 MONTH 1060 00:51:28,189 --> 00:51:30,525 FOLLOW UPS, SEE HOW YOU ARE 1061 00:51:30,525 --> 00:51:32,861 DOING TWO YEARS LATER, 1062 00:51:32,861 --> 00:51:35,897 94 PERCENT HAD SOME FORM OF 1063 00:51:35,897 --> 00:51:40,235 CHRONIC COMPLICATIONS AND IT RAN 1064 00:51:40,235 --> 00:51:43,939 THE GAMUT. 1065 00:51:43,939 --> 00:51:46,341 DISPHASIA, BIOREFLUX WHICH IS 1066 00:51:46,341 --> 00:51:47,542 HORRIBLE FOR PATIENTS, AND THIS 1067 00:51:47,542 --> 00:51:50,679 IS A STUDY I AM NOT TALKING 1068 00:51:50,679 --> 00:51:53,915 ABOUT BUT DOCTOR GAMBLE DID THIS 1069 00:51:53,915 --> 00:51:55,984 DECISION-MAKING AND REGRET STUDY 1070 00:51:55,984 --> 00:51:58,053 PUBLISHED IN ANOTHER JOURNAL. 1071 00:51:58,053 --> 00:52:00,522 THE IMPACTS ON MENTAL HEALTH ARE 1072 00:52:00,522 --> 00:52:03,258 REALLY SIGNIFICANT AND WE HAVE 1073 00:52:03,258 --> 00:52:05,226 ONLY BEGUN TO SCRATCH THE 1074 00:52:05,226 --> 00:52:07,429 SURFACE ON THIS TOPIC, OKAY? 1075 00:52:07,429 --> 00:52:09,064 BUT TAKING OUT PEOPLE'S STOMACH 1076 00:52:09,064 --> 00:52:13,001 IS NOT LIKE OH GREAT, YOU 1077 00:52:13,001 --> 00:52:15,303 PREVENTED CANCER, WE'RE CAUSING 1078 00:52:15,303 --> 00:52:15,570 PROBLEMS. 1079 00:52:15,570 --> 00:52:19,708 SO LET'S GO BACK TO THE 1080 00:52:19,708 --> 00:52:21,876 11-YEAR-OLD, CDH1 GERMLINE 1081 00:52:21,876 --> 00:52:22,978 PATHOGENIC VARIANT, IF HE DIDN'T 1082 00:52:22,978 --> 00:52:24,012 HAVE THE GERMLINE YOU WOULD SAY 1083 00:52:24,012 --> 00:52:26,681 YOU ARE NOT GOING TO TAKE OUT 1084 00:52:26,681 --> 00:52:30,385 THE STOMACH BUT HE HAD A 1085 00:52:30,385 --> 00:52:32,754 PATHOLOG Y REPORT THAT SAID 1086 00:52:32,754 --> 00:52:35,590 CANCER AND THEY INITIATED 1087 00:52:35,590 --> 00:52:35,924 CHEMOTHERAPY. 1088 00:52:35,924 --> 00:52:40,061 WELL BASED ON WHAT WE SHOWED YOU 1089 00:52:40,061 --> 00:52:40,895 THAT THE SIGNET RING CELLS ARE 1090 00:52:40,895 --> 00:52:42,430 THERE IN ALL THESE PATIENTS AND 1091 00:52:42,430 --> 00:52:44,432 WE HAVE BEEN DOING SURVEILLANCE 1092 00:52:44,432 --> 00:52:46,635 ON HUNDREDS OF PEOPLE FOR YEARS 1093 00:52:46,635 --> 00:52:51,406 AT NIH AND NONE OF THEM 1094 00:52:51,406 --> 00:52:54,743 DEVELOPED MORE CANCER OR DIED OF 1095 00:52:54,743 --> 00:52:58,113 CANCER, ONLY TWO DEVELOPED STAGE 1096 00:52:58,113 --> 00:53:01,883 2 CANCER WHICH WE INTERVENED ON. 1097 00:53:01,883 --> 00:53:06,187 SO WE JUST FOLLOWED WITH CHEMO 1098 00:53:06,187 --> 00:53:15,697 THEIR. CHEMOTHERAPY. 1099 00:53:15,697 --> 00:53:18,533 WE INITIATED ENDOSCO PIC 1100 00:53:18,533 --> 00:53:20,368 SURVEILLANCE AT NIH BECAUSE MOST 1101 00:53:20,368 --> 00:53:21,770 PEOPLE DON'T WANT TO AND WE HAVE 1102 00:53:21,770 --> 00:53:23,538 BEEN FOLLOWING THEM AND MOST OF 1103 00:53:23,538 --> 00:53:25,507 THEM ARE NOT DEVELOPING CANCER. 1104 00:53:25,507 --> 00:53:34,649 AND OUR GOAL IS TO PREVENT 1105 00:53:34,649 --> 00:53:34,949 GASTRECTOMY. 1106 00:53:34,949 --> 00:53:37,786 SO I WILL SUMMARIZE HOW I THINK 1107 00:53:37,786 --> 00:53:40,655 OUR RESEARCH AFFECTED THIS CHILD 1108 00:53:40,655 --> 00:53:42,924 BUT I THINK IS IMPACTING LOTS OF 1109 00:53:42,924 --> 00:53:44,292 PEOPLE OUT THERE. 1110 00:53:44,292 --> 00:53:47,228 Dr. KIM, I SHOW HER PICTURE 1111 00:53:47,228 --> 00:53:57,639 BECAUSE SHE IS THE PATH 1112 00:53:59,841 --> 00:54:01,476 PATHOLOGIST FOR OCCULT SRC 1113 00:54:01,476 --> 00:54:06,114 PRESENT IN NEARLY ALL CDH1 1114 00:54:06,114 --> 00:54:08,249 VARIANT CARRIERS. 1115 00:54:08,249 --> 00:54:11,019 REMEMBER, WE'RE TAKING RANDOM 1116 00:54:11,019 --> 00:54:12,153 SHOTS OF THE STOMACH BUT THEY 1117 00:54:12,153 --> 00:54:14,289 ARE THERE AND THEN GRACE TOLD 1118 00:54:14,289 --> 00:54:16,124 YOU LIFETIME CANCER RISKS IS 1119 00:54:16,124 --> 00:54:18,460 PROBABLY LOWER THAN ORIGINAL 1120 00:54:18,460 --> 00:54:19,961 ESTIMATES OF LIKE 80 PERCENT, 1121 00:54:19,961 --> 00:54:20,261 RIGHT? 1122 00:54:20,261 --> 00:54:23,164 AND WE JUST OBSERVED PATIENTS IN 1123 00:54:23,164 --> 00:54:24,666 FAMILIES, WE SEE PEOPLE WITH 1124 00:54:24,666 --> 00:54:27,469 FAMILY MEMBERS IN THEIR 80s 1125 00:54:27,469 --> 00:54:29,537 WITH A CDH1 VARIANT ALIVE AND 1126 00:54:29,537 --> 00:54:32,073 WELL AT 80 AND NEVER DEVELOPED 1127 00:54:32,073 --> 00:54:32,307 CANCER. 1128 00:54:32,307 --> 00:54:33,541 SO CLEARLY WE'RE STARTING TO 1129 00:54:33,541 --> 00:54:36,778 SHOW A PICTURE OF THESE CANCERS 1130 00:54:36,778 --> 00:54:39,414 THAT ARE DETECTED IN PEOPLE THAT 1131 00:54:39,414 --> 00:54:41,149 MAYBE DON'T TURN INTO CANCER. 1132 00:54:41,149 --> 00:54:44,185 SO NOW THAT TELLS US WHY 1133 00:54:44,185 --> 00:54:46,154 SURVEILLANCE IS PROBABLY A 1134 00:54:46,154 --> 00:54:56,598 REASONABLE ALTERNATIVE TO 1135 00:54:56,598 --> 00:54:57,298 PROFYLACTIC GASTRONOMY AND AGAIN 1136 00:54:57,298 --> 00:55:01,703 I LIKE DOING GASTRECTOMIES BUT 1137 00:55:01,703 --> 00:55:02,837 THE CONSEQUENCES ARE SEVERE. 1138 00:55:02,837 --> 00:55:05,940 SO OUR CONCLUSIONS ARE MAYBE 1139 00:55:05,940 --> 00:55:07,442 THESE SIGNET RING CELLS THAT WE 1140 00:55:07,442 --> 00:55:10,779 FIND IN THE GERMLINE OF CDH1 1141 00:55:10,779 --> 00:55:13,581 CARRIERS ARE NOT CANCER BUT 1142 00:55:13,581 --> 00:55:14,682 PRECANCERS, RIGHT? 1143 00:55:14,682 --> 00:55:16,851 NOT ALL OF THEM ARE GOING TO 1144 00:55:16,851 --> 00:55:17,519 TURN INTO CANCER. 1145 00:55:17,519 --> 00:55:18,920 SO THAT LEADS TO THE RESEARCH 1146 00:55:18,920 --> 00:55:20,455 QUESTIONS AND I WILL TRY TO DO 1147 00:55:20,455 --> 00:55:22,090 THIS IN THE LAST FEW MINUTES. 1148 00:55:22,090 --> 00:55:24,192 WHAT ACCOUNTS FOR THIS DROPOFF? 1149 00:55:24,192 --> 00:55:26,127 WE FIND THE CELLS IN EVERYBODY 1150 00:55:26,127 --> 00:55:28,997 WITH THE MUTATION BUT NOT 1151 00:55:28,997 --> 00:55:30,732 EVERYBODY DEVELOPS CANCER. 1152 00:55:30,732 --> 00:55:31,466 WHY? 1153 00:55:31,466 --> 00:55:34,969 WHAT IS THE PHENOTYPE OF THOSE 1154 00:55:34,969 --> 00:55:36,871 LITTLE SIGNET RING CELLS, WHY 1155 00:55:36,871 --> 00:55:47,415 ARE THEY SO UNIQUE HOR OR HOW 1156 00:55:47,715 --> 00:55:51,786 ARE THEY DIFFERENT FROM ADVANCED 1157 00:55:51,786 --> 00:55:52,687 CANCER? 1158 00:55:52,687 --> 00:55:55,557 SO TIM IS A BIOLOGIST, HELPED ME 1159 00:55:55,557 --> 00:55:58,893 OUT IN THE LAB, HOPE HE DOESN'T 1160 00:55:58,893 --> 00:55:59,260 MIND. 1161 00:55:59,260 --> 00:56:01,062 WE STARTED THIS MANY YEARS AGO 1162 00:56:01,062 --> 00:56:07,602 AND THEN BEN FINISHED IT BUT WE 1163 00:56:07,602 --> 00:56:10,738 DID BULK INVESTIGATION OF THESE 1164 00:56:10,738 --> 00:56:12,707 SIGNET RING CELLS AND SHOWED 1165 00:56:12,707 --> 00:56:15,176 VERY SIMPLY THAT THE SRC 1166 00:56:15,176 --> 00:56:18,813 COMPARED TO NEP WHICH IS NORMAL 1167 00:56:18,813 --> 00:56:20,915 EPITHELIUM OF THE STOMACH HAD 1168 00:56:20,915 --> 00:56:21,950 SOME OBVIOUS CHANGES. 1169 00:56:21,950 --> 00:56:28,323 SO DOWN REGULATION OF NORMAL 1170 00:56:28,323 --> 00:56:30,692 GASTRIC GENES, THIS IS THE 1171 00:56:30,692 --> 00:56:31,259 PRETTY TON PUMP. 1172 00:56:31,259 --> 00:56:34,929 BUT GUESS WHAT? 1173 00:56:34,929 --> 00:56:38,099 THE SIGNET CELLS DIDN'T SHOW ANY 1174 00:56:38,099 --> 00:56:40,001 REGULATION OF WHAT YOU WOULD 1175 00:56:40,001 --> 00:56:41,669 CONSIDER TO BE CANCER, RIGHT? 1176 00:56:41,669 --> 00:56:49,544 WE DIDN'T SEE ANY DYSFUNCTION OR 1177 00:56:49,544 --> 00:56:51,679 UPREGULATION OF ONCOGENIC 1178 00:56:51,679 --> 00:56:52,513 PATHWAYS? 1179 00:56:52,513 --> 00:56:55,550 BEN SAID GEE, I SEE A LOT OF 1180 00:56:55,550 --> 00:56:59,187 CHANGES WITH IMMUNE SIGNALING, T 1181 00:56:59,187 --> 00:57:01,923 CELL, P CELL EXHAUSTION, STUFF 1182 00:57:01,923 --> 00:57:04,592 LIKE THAT SO THEN BEN PUBLISHED 1183 00:57:04,592 --> 00:57:08,129 THIS PAPER SAYING DOES THE 1184 00:57:08,129 --> 00:57:09,364 ENVIRONMENT INFLUENCE THE 1185 00:57:09,364 --> 00:57:13,034 BEHAVIOR OF THOSE SIGNET RING 1186 00:57:13,034 --> 00:57:13,234 CELLS? 1187 00:57:13,234 --> 00:57:13,902 IT MIGHT. 1188 00:57:13,902 --> 00:57:14,569 WE DON'T KNOW. 1189 00:57:14,569 --> 00:57:17,805 BUT THEN HE LOOKED AT THE 1190 00:57:17,805 --> 00:57:21,309 EXPRESS GENES AND SAID WE DON'T 1191 00:57:21,309 --> 00:57:23,945 SEE ANY UPREGULATION SIGNALING 1192 00:57:23,945 --> 00:57:27,815 BUT BOY TO WE SEE ENRICHMENT IN 1193 00:57:27,815 --> 00:57:29,217 C CELL SIGNALING, ET CETERA. 1194 00:57:29,217 --> 00:57:32,186 SO I WON'T GO INTO IT TODAY BUT 1195 00:57:32,186 --> 00:57:38,526 WE ARE USING THIS TO EXPLORE 1196 00:57:38,526 --> 00:57:46,834 CANCER PREVENTION IMIMMUNOLOGIC 1197 00:57:46,834 --> 00:57:47,235 STRATEGIES. 1198 00:57:47,235 --> 00:57:51,339 SO WE WERE GETTING READY TO PUT 1199 00:57:51,339 --> 00:57:52,206 TOGETHER THIS MANUSCRIPT, WE USE 1200 00:57:52,206 --> 00:57:54,909 THE HOT THING, THE NANOSTRING 1201 00:57:54,909 --> 00:57:58,446 PLATFORM TO LOOK AT THOSE SIGNET 1202 00:57:58,446 --> 00:58:02,250 RING CELLS COMPARED TO NORMAL 1203 00:58:02,250 --> 00:58:04,118 GASTRIC EPITHELIUM. 1204 00:58:04,118 --> 00:58:06,387 AND WE SAW OBVIOUSLY DOWN 1205 00:58:06,387 --> 00:58:08,489 REGULATION OF THE CDH1, Dr. 1206 00:58:08,489 --> 00:58:11,359 KIM SHOWED YOU WITH THE 1207 00:58:11,359 --> 00:58:12,961 CHEMISTRY. 1208 00:58:12,961 --> 00:58:20,435 AND THE SIGNET CELLS SHOW UP IN 1209 00:58:20,435 --> 00:58:21,669 YELLOW, AND THE CELLS OVER HERE 1210 00:58:21,669 --> 00:58:24,472 THAT SHOULD BE LIGHTING UP IN 1211 00:58:24,472 --> 00:58:26,708 BLUE ARE ABSENT SO IT IS LOST. 1212 00:58:26,708 --> 00:58:28,109 THAT IS GREAT SO THAT TELLS US 1213 00:58:28,109 --> 00:58:30,144 IT IS LIKE A INITIATING EVENT. 1214 00:58:30,144 --> 00:58:33,181 SO WHAT ELSE IS GOING ON? THE 1215 00:58:33,181 --> 00:58:35,049 CELLS ARE INVADING THE BASEMENT 1216 00:58:35,049 --> 00:58:39,253 MEMBRANE SO NOT SURPRISINGLY WE 1217 00:58:39,253 --> 00:58:48,863 SAW DID HE GO DAYS OF FCM, NO 1218 00:58:48,863 --> 00:58:50,865 DIFFERENCE IN EXPRESSION OF 1219 00:58:50,865 --> 00:58:53,234 MARKERS OF TUMOR PROLIFERATION 1220 00:58:53,234 --> 00:58:55,737 SO WE LOOKED AT PATIENTS WITH 1221 00:58:55,737 --> 00:58:57,772 MORE ADVANCED CANCERS I OPERATED 1222 00:58:57,772 --> 00:58:59,540 ON ON ANOTHER PROTOCOL. 1223 00:58:59,540 --> 00:59:00,174 AND GUESS WHAT? 1224 00:59:00,174 --> 00:59:01,843 NOW ALL OF A SUDDEN, YOU SAW 1225 00:59:01,843 --> 00:59:09,584 WHAT YOU EXPECTED TO SEE, RIGHT? 1226 00:59:09,584 --> 00:59:12,920 THE MORE ADVANCEDLESIONS, 1227 00:59:12,920 --> 00:59:16,224 GREATER THAN T2, THEY LOOKED SO 1228 00:59:16,224 --> 00:59:21,496 DIFFERENT THAN THE SIG NET 1229 00:59:21,496 --> 00:59:25,900 CELLS, SO WE SAW IN THE ADVANCED 1230 00:59:25,900 --> 00:59:30,104 CANCERS THE UPREGULATION OF 1231 00:59:30,104 --> 00:59:31,839 MYCO, OR MET, BUT THEY WEREN'T 1232 00:59:31,839 --> 00:59:35,743 THERE IN THE SIGNET CELLS. 1233 00:59:35,743 --> 00:59:37,645 OKAY THE THING IS ACTING FUNNY 1234 00:59:37,645 --> 00:59:40,648 SO IT MUST BE TIME TO END. 1235 00:59:40,648 --> 00:59:44,952 SO TO SUMMARIZE THIS ANALYSIS SO 1236 00:59:44,952 --> 00:59:47,688 FAR, THESE CDH PATIENTS START 1237 00:59:47,688 --> 00:59:53,761 HERE, THEY ARE HETEROZYG OUS AND 1238 00:59:53,761 --> 00:59:56,230 WHY THEY REAR THEIR UGLY HEAD, 1239 00:59:56,230 --> 00:59:57,031 WE DON'T KNOW. 1240 00:59:57,031 --> 00:59:58,433 THEY DON'T REALLY ACT LIKE 1241 00:59:58,433 --> 01:00:01,002 CANCERS AND THE ADVANCED CANCERS 1242 01:00:01,002 --> 01:00:02,136 CLEARLY LOOK DIFFERENT AND WE 1243 01:00:02,136 --> 01:00:03,938 NEED TO FIGURE OUT WHAT IT IS OR 1244 01:00:03,938 --> 01:00:08,543 WHY IT IS THAT THEY DO THAT. 1245 01:00:08,543 --> 01:00:11,179 SO TAKEHOME MESSAGE, 91 PERCENT 1246 01:00:11,179 --> 01:00:14,482 OF THE PATHOGENIC CARRIERS HAVE 1247 01:00:14,482 --> 01:00:17,985 THESE SIGNET CANCER CELLS HIDING 1248 01:00:17,985 --> 01:00:23,191 IN THEIR STOMACHS BUT THE 1249 01:00:23,191 --> 01:00:28,729 GASTRIC ACTIVE CANCER IS LOW, 1250 01:00:28,729 --> 01:00:37,772 AND WHEN I PERFORM THE 1251 01:00:37,772 --> 01:00:48,249 GASTRECTOMY, IT HAS CHRONIC 1252 01:00:49,117 --> 01:00:55,289 SEGUELAE AND THE EARLY SIGNET 1253 01:00:55,289 --> 01:00:58,292 RING CELL LESIONS ARE 1254 01:00:58,292 --> 01:00:59,060 NONOBLIGATED CANCERS. 1255 01:00:59,060 --> 01:01:00,595 SO OUR RESEARCH HAS IMPACT ON 1256 01:01:00,595 --> 01:01:01,829 INDIVIDUALS AND WE ARE OFFERING 1257 01:01:01,829 --> 01:01:05,133 HOPE TO PATIENTS WHO WERE TOLD 1258 01:01:05,133 --> 01:01:09,370 GASTRIC CANCER IS ALL BUT 1259 01:01:09,370 --> 01:01:12,540 CERTAIN AND GASTRECTOMY IS THE 1260 01:01:12,540 --> 01:01:15,743 ONLY OPTION. 1261 01:01:15,743 --> 01:01:18,412 HERE AT THE NIH AND PEOPLE STILL 1262 01:01:18,412 --> 01:01:21,382 WITH ME, DESPITE THE CLINICAL 1263 01:01:21,382 --> 01:01:23,918 CENTER AT NIH, WE LIKE TO TALK 1264 01:01:23,918 --> 01:01:25,419 ABOUT SOME THINGS THAT GET IN 1265 01:01:25,419 --> 01:01:28,189 OUR WAY, WE CAN STILL DO 1266 01:01:28,189 --> 01:01:29,790 MEANINGFUL WORK BUT WE CAN'T 1267 01:01:29,790 --> 01:01:31,058 TAKE IT FOR GRANTED. 1268 01:01:31,058 --> 01:01:32,994 IT REQUIRES WE SAY YES MORE THAN 1269 01:01:32,994 --> 01:01:35,830 WE SAY NO AND OF COURSE WE CAN 1270 01:01:35,830 --> 01:01:38,599 DO THAT, NOT NAH, WE CAN'T 1271 01:01:38,599 --> 01:01:40,601 REALLY DO THAT, RIGHT? 1272 01:01:40,601 --> 01:01:42,069 AND IT MEANS WE TEND TO PEOPLE 1273 01:01:42,069 --> 01:01:43,771 BECAUSE THEY ARE THE ONES THAT 1274 01:01:43,771 --> 01:01:44,672 MAKE THE INSTITUTION. 1275 01:01:44,672 --> 01:01:47,108 WE HAVE TO GROW PEOPLE, WE HAVE 1276 01:01:47,108 --> 01:01:49,010 TO NURTURE THEM AND ALL KOPT 1277 01:01:49,010 --> 01:01:51,846 PWAOUGSZ ARE IMPORTANT 1278 01:01:51,846 --> 01:01:52,613 REGARDLESS OF THE INDIVIDUALS' 1279 01:01:52,613 --> 01:01:53,514 TITLE OR STATUS. 1280 01:01:53,514 --> 01:01:55,483 SO WITH THAT I WANT TO THANK 1281 01:01:55,483 --> 01:01:57,852 EVERYBODY ON MY TEAM AND THE 1282 01:01:57,852 --> 01:01:58,786 EXTENDED TEAM, THANK YOU VERY 1283 01:01:58,786 --> 01:02:00,655 MUCH FOR YOUR TIME AND ATTENTION 1284 01:02:00,655 --> 01:02:02,990 AND SORRY I WENT A MINUTE OR TWO 1285 01:02:02,990 --> 01:02:04,525 MINUTES OVER. 1286 01:02:04,525 --> 01:02:10,765 [APPLAUSE] 1287 01:02:10,765 --> 01:02:14,936 >> THANK YOU FOR THIS PHENOMENAL 1288 01:02:14,936 --> 01:02:15,369 TALK. 1289 01:02:15,369 --> 01:02:18,673 JUST GOING A LITTLE BIT OVER, WE 1290 01:02:18,673 --> 01:02:21,742 WILL ASK IF ANYBODY HAS A 1291 01:02:21,742 --> 01:02:23,277 QUESTION TO EITHER DIRECTLY 1292 01:02:23,277 --> 01:02:24,545 FORWARD IT TO JEREMY OR MYSELF 1293 01:02:24,545 --> 01:02:26,881 AND THEN WE WILL WRAP IT UP FOR 1294 01:02:26,881 --> 01:02:27,381 TODAY. 1295 01:02:27,381 --> 01:02:29,483 THANK YOU ALL FOR BEING HERE 1296 01:02:29,483 --> 01:02:30,451 VIRTUALLY AND THANKS FOR DOING 1297 01:02:30,451 --> 01:02:34,322 WHAT YOU ARE DOING AS THE 1298 01:02:34,322 --> 01:02:37,692 MULTIDISCIPLINARY TOO MANY AND 1299 01:02:37,692 --> 01:02:39,293 -- TEAM AND ONE OF THE MAJOR 1300 01:02:39,293 --> 01:02:41,629 STRENGTHS OF OUR HOSPITAL. 1301 01:02:41,629 --> 01:02:51,839 THANK YOU.