1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,640 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,640 --> 00:00:48,160 >>OUR SPEAKER TODAY 12 00:00:48,160 --> 00:01:00,280 IS DR. ANDREA HAYES-DIXON. 13 00:01:00,280 --> 00:01:01,880 ON OCTOBER 22 SHE WAS APPOINTED 14 00:01:01,880 --> 00:01:04,120 AS DEAN OF MEDICINE AND SERVES 15 00:01:04,120 --> 00:01:09,680 AS ASSOCIATE CANCER CENTER AT 16 00:01:09,680 --> 00:01:09,920 HOWARD. 17 00:01:09,920 --> 00:01:18,040 SHE EARNED HER MD DEGREE FROM 18 00:01:18,040 --> 00:01:19,400 DARTMOUTH COLLEGE. 19 00:01:19,400 --> 00:01:21,400 SHE ALSO COMPLETED A MOLECULAR 20 00:01:21,400 --> 00:01:22,920 BIOLOGY FELLOWSHIP AT THE 21 00:01:22,920 --> 00:01:23,840 UNIVERSITY OF CALIFORNIA 22 00:01:23,840 --> 00:01:30,040 SAN FRANCISCO AND WENT ON TO 23 00:01:30,040 --> 00:01:31,720 COMPLETE A PEDEIATIC 24 00:01:31,720 --> 00:01:32,760 PHARMACOLOGY RESIDENCE IN 25 00:01:32,760 --> 00:01:33,920 MEMPHIS, TENNESSEE. 26 00:01:33,920 --> 00:01:36,280 SHE CONTINUED HER ACADEMIC 27 00:01:36,280 --> 00:01:37,840 JOURNEY BY COMPLETING HER 28 00:01:37,840 --> 00:01:40,160 PEDIATRIC SURGERY FOALSHIP AT 29 00:01:40,160 --> 00:01:41,920 THE TORONTO HOSPITAL FOR SICK 30 00:01:41,920 --> 00:01:43,720 CHILDREN. 31 00:01:43,720 --> 00:01:45,600 AND IN 2002, DR. HAY ESTIMATE 32 00:01:45,600 --> 00:01:48,120 THAD DIXON BECAME THE FIRST 33 00:01:48,120 --> 00:01:49,400 BLACK PEDIATRIC BOARD CERTIFIED 34 00:01:49,400 --> 00:01:50,840 SURGEON IN THE UNITED STATES, 35 00:01:50,840 --> 00:01:53,800 SHE WENT WENT ON TO COMPLETE A 36 00:01:53,800 --> 00:01:56,400 MELANOMA AND SARCOMA FELLOWSHIP 37 00:01:56,400 --> 00:01:59,240 IN TEXAS AT M. D. ANDERSON 38 00:01:59,240 --> 00:02:00,240 CANCER CENTER WHILE SHE WAS 39 00:02:00,240 --> 00:02:02,880 RECRUITED TO STAY ONAC FACULTY, 40 00:02:02,880 --> 00:02:05,400 WHILE THERE SHE WAS AWARDED 41 00:02:05,400 --> 00:02:06,880 ROBERT WOOD JOHNSON FOUNDATION 42 00:02:06,880 --> 00:02:11,240 THAT ALLOWED HER TO FUND HER 43 00:02:11,240 --> 00:02:16,840 RESEARCH IN MELANOMA SARCOMA AND 44 00:02:16,840 --> 00:02:17,440 ANGIOGENESIS. 45 00:02:17,440 --> 00:02:17,920 SHE SIGN SIMULTANEOUSLY 46 00:02:17,920 --> 00:02:20,040 CONDUCTED CLINICAL RESEARCH AND 47 00:02:20,040 --> 00:02:21,080 COMPLEELTED THE FIRST 48 00:02:21,080 --> 00:02:24,040 CYTOREDUCTIVE SURGERY AND HYPER 49 00:02:24,040 --> 00:02:26,640 THERMOGENESISSIC INTRA PERO TON 50 00:02:26,640 --> 00:02:31,000 EEL CHEMO TERRAPY WITH 51 00:02:31,000 --> 00:02:32,320 SARICOSEIS IN 2005. 52 00:02:32,320 --> 00:02:35,320 SHE LATER ESTABLISHED SAFE CHEMO 53 00:02:35,320 --> 00:02:37,280 THERAPY DOSING USING HIPECKS FOR 54 00:02:37,280 --> 00:02:37,760 PATIENTS. 55 00:02:37,760 --> 00:02:39,480 SHE CONTINUED TO IMPACT THE 56 00:02:39,480 --> 00:02:47,000 FIELD OF SARCOMA BY MASSING THE 57 00:02:47,000 --> 00:02:51,720 LARGE OF RESEARCH INFORMATION. 58 00:02:51,720 --> 00:02:53,080 IT'S AN AGGRESSIVE FORM OF 59 00:02:53,080 --> 00:02:57,600 CANCER AND VIA RESECTION AND 60 00:02:57,600 --> 00:02:59,880 HYPO[INDISCERNIBLE] HAS IMPROVED 61 00:02:59,880 --> 00:03:02,760 SURVIVAL FROM 30-60% IN THIS 62 00:03:02,760 --> 00:03:03,920 POPULATION. 63 00:03:03,920 --> 00:03:04,600 DR. DIXON CONTINUES TO RECEIVE 64 00:03:04,600 --> 00:03:06,680 FUNDING IF ARE HER RESEARCH AND 65 00:03:06,680 --> 00:03:10,680 IS NATIONALLY AND INTERNATIONAL 66 00:03:10,680 --> 00:03:13,080 KNOWN FOR PIONEERING WORK FOR 67 00:03:13,080 --> 00:03:13,960 [INDISCERNIBLE] CHILDREN. 68 00:03:13,960 --> 00:03:15,480 DURING HER TIME AT M. D. 69 00:03:15,480 --> 00:03:17,240 ANDERSON SHE SERVED AS CHIEF THE 70 00:03:17,240 --> 00:03:18,960 SURGERY AND SHE WENT ON TO 71 00:03:18,960 --> 00:03:20,840 BECOME THE SURGEON AND CHIEF AND 72 00:03:20,840 --> 00:03:23,320 DIVISION AND CHIEF AT THE 73 00:03:23,320 --> 00:03:24,720 PEDIATRIC UNIVERSITY AT UNC 74 00:03:24,720 --> 00:03:26,160 CHILDREN'S HOSPITAL PRIOR TO 75 00:03:26,160 --> 00:03:27,800 RETURNING HER CURRENT ESTEEMED 76 00:03:27,800 --> 00:03:31,760 ROLE AT HOWARD. 77 00:03:31,760 --> 00:03:33,160 ADDITIONALLY SHE SERVED ON THE 78 00:03:33,160 --> 00:03:35,000 EXECUTIVE COMMITTEE OF THE 79 00:03:35,000 --> 00:03:35,720 COMRN'S ONCOLOGY GROUP SARCOMA 80 00:03:35,720 --> 00:03:37,400 COMMITTEE FOR THE PAST 10 YEARS, 81 00:03:37,400 --> 00:03:39,160 A POSITION SHARED BY ONLY 2 82 00:03:39,160 --> 00:03:40,920 OTHER PEDIATRIC SURGEONS IN THE 83 00:03:40,920 --> 00:03:41,160 COUNTRY. 84 00:03:41,160 --> 00:03:44,440 SHE EARNED MEMBERSHIP INTO THE 85 00:03:44,440 --> 00:03:45,160 AMERICAN SURGICAL ASSOCIATION 86 00:03:45,160 --> 00:03:46,600 AND SERVED AS THE CHAIR OF THE 87 00:03:46,600 --> 00:03:48,320 CANCER COMMITTEE FOR THE 88 00:03:48,320 --> 00:03:51,360 AMERICAN PEDIATRIC SURGICAL 89 00:03:51,360 --> 00:03:51,680 ASSOCIATION. 90 00:03:51,680 --> 00:03:53,560 SHE HAS ALSO BEEN SELECTED TO 91 00:03:53,560 --> 00:03:55,000 THE PEDIATRIC DISEASE QUERY, A 92 00:03:55,000 --> 00:03:56,640 NATIONAL COMMITTEE THAT VETS 93 00:03:56,640 --> 00:03:58,520 EVERY PUBLICATION ON PEDIATRIC 94 00:03:58,520 --> 00:03:59,800 CANCER AND SUMMARIZES THEM FOR 95 00:03:59,800 --> 00:04:01,240 THE NATIONAL CANCER INSTITUTE. 96 00:04:01,240 --> 00:04:02,960 SHE SERVED AS A PAST PRESIDENT 97 00:04:02,960 --> 00:04:04,800 FOR THE SOCIETY OF BLACK 98 00:04:04,800 --> 00:04:06,000 ACADEMIC SURGEONS AND IS A 99 00:04:06,000 --> 00:04:08,640 REGION OF THE AMERICAN COLLEGE 100 00:04:08,640 --> 00:04:10,200 OF SURGEONS. 101 00:04:10,200 --> 00:04:11,600 DR. HAY ESTIMATE THAD DIXON WAS 102 00:04:11,600 --> 00:04:12,680 APPOINTED BY FORMER PRESIDENT 103 00:04:12,680 --> 00:04:14,320 TRUMP TO THE NATIONAL CANCER 104 00:04:14,320 --> 00:04:15,400 ADVISORY BOARD WHICH REPORTS TO 105 00:04:15,400 --> 00:04:16,840 THE DIRECTOR OF THE NATIONAL 106 00:04:16,840 --> 00:04:18,640 CANCER INSTITUTE AND THE 107 00:04:18,640 --> 00:04:22,880 SECRETARY OF HEALTH. 108 00:04:22,880 --> 00:04:24,760 FINALLY DR. HAYES-DIXON HAS 109 00:04:24,760 --> 00:04:28,200 PUBLISHED DOZENS OF BOOKS AND 110 00:04:28,200 --> 00:04:30,120 PUBLICATIONS AND ENJOYS FAC ULGT 111 00:04:30,120 --> 00:04:30,760 EXPE RESIDENTS. 112 00:04:30,760 --> 00:04:34,760 NOW PLEASE HELP ME WELCOME OUR 113 00:04:34,760 --> 00:04:39,320 SPEAKER DR. HAYES-DIXON WHOSE 114 00:04:39,320 --> 00:04:42,720 PRESENTATION IS ENTITLED THE 115 00:04:42,720 --> 00:04:44,520 JOURNEY TO DISCOVERING A NOVEL 116 00:04:44,520 --> 00:04:47,640 PROCEDURE FOR CHILDREN WITH 117 00:04:47,640 --> 00:04:48,200 ADVANCE ABDOMINAL TUMORS. 118 00:04:48,200 --> 00:04:50,840 >>THANK YOU FOR THE PHENOMENAL 119 00:04:50,840 --> 00:04:52,480 INTRODUCTION, AND I'M VERY 120 00:04:52,480 --> 00:04:54,080 PLEASED TO BE WITH YOU TODAY TO 121 00:04:54,080 --> 00:04:57,840 TALK ABOUT MY JOURNEY IN TRYING 122 00:04:57,840 --> 00:05:00,920 TO ACHIEVE SOME UNDERSTANDING OF 123 00:05:00,920 --> 00:05:01,200 A VERY RARE CANCER THAT I TAKE 124 00:05:01,200 --> 00:05:02,160 CARE OF. 125 00:05:02,160 --> 00:05:03,720 WHAT I WANT TO SHARE WITH YOU 126 00:05:03,720 --> 00:05:04,960 TODAY IS WHAT'S HAPPENED OVER 127 00:05:04,960 --> 00:05:06,840 THE LAST 20 YEARS OR SO OF MY 128 00:05:06,840 --> 00:05:09,520 CAREER AND IN THAT I HAVE REALLY 129 00:05:09,520 --> 00:05:11,320 LEARNED A LOT AND HOPE TO SHARE 130 00:05:11,320 --> 00:05:11,880 THAT WITH YOU. 131 00:05:11,880 --> 00:05:13,280 FIRST OF ALL I HAVE NO 132 00:05:13,280 --> 00:05:14,080 DISCLOSURES AND I HOPE BY THE 133 00:05:14,080 --> 00:05:16,320 END OF THE TALK, YOU WOULD BE 134 00:05:16,320 --> 00:05:17,960 ABLE TO UNDERSTAND HOW IT IS IN 135 00:05:17,960 --> 00:05:19,400 DEVELOPING A PATH TO DISCOVERING 136 00:05:19,400 --> 00:05:21,160 SOMETHING THAT'S NEW, HOW DO YOU 137 00:05:21,160 --> 00:05:21,440 INNOVATE. 138 00:05:21,440 --> 00:05:23,080 WHAT QUESTIONS DO YOU ASK TO 139 00:05:23,080 --> 00:05:24,880 UNDERSTAND A DISEASE THAT HASN'T 140 00:05:24,880 --> 00:05:26,200 BEEN OOBD IN THE PAST. 141 00:05:26,200 --> 00:05:29,160 HOW TO APPROACH WHAT HAS BEEN 142 00:05:29,160 --> 00:05:30,680 CALLED AN IMPOSSIBLE TASK, WHAT 143 00:05:30,680 --> 00:05:35,760 IS THIS RARE TUMOR I TAKE CARE 144 00:05:35,760 --> 00:05:37,600 OF CAUSE TD DESMODEL CITIZEN 145 00:05:37,600 --> 00:05:39,240 PLASTIC SMALL ROUND CELL TUMOR, 146 00:05:39,240 --> 00:05:42,800 SO WHAT ARE THE OUTCOMES OF 147 00:05:42,800 --> 00:05:43,240 THESE APPLICATIONS. 148 00:05:43,240 --> 00:05:44,240 SO BILET END OF THE TALK, I HOPE 149 00:05:44,240 --> 00:05:46,200 YOU WILL UNDERSTAND OF HOW I 150 00:05:46,200 --> 00:05:50,200 THOUGHT THROUGH THE PROCESS OF 151 00:05:50,200 --> 00:05:52,840 UNDERSTANDING THE ORIGIN OF THE 152 00:05:52,840 --> 00:05:54,240 BASIC TUMOR, TAKING THE SCIENCE 153 00:05:54,240 --> 00:05:55,680 BACK TO MY LABORATORY AND 154 00:05:55,680 --> 00:05:58,200 FIGURING OUT HOW THE TUMOR GROWS 155 00:05:58,200 --> 00:06:01,600 AND SPREADS. 156 00:06:01,600 --> 00:06:02,880 SO MULTIPLE ABDOMINAL IMPLANTS 157 00:06:02,880 --> 00:06:05,120 IS HOW I WAS INTRODUCED TO THIS 158 00:06:05,120 --> 00:06:05,520 DISEASE. 159 00:06:05,520 --> 00:06:07,520 SO WHEN I WAS IN TRAINING I MET 160 00:06:07,520 --> 00:06:10,360 A 12 YEAR-OLD BOY WHO WE OPENED 161 00:06:10,360 --> 00:06:13,560 THROUGH THE OPERATING ROOM 162 00:06:13,560 --> 00:06:15,960 THROUGH A LONG MIDLINE INCISION 163 00:06:15,960 --> 00:06:17,400 AND ENCOUNTERED HUNDREDS OF 164 00:06:17,400 --> 00:06:19,920 THOUSANDS OF TUMORS IN THE 165 00:06:19,920 --> 00:06:22,440 ABDOMEN, AND MY TEACHER SAID 166 00:06:22,440 --> 00:06:23,520 THERE'S NOTHING WE CAN DO FOR 167 00:06:23,520 --> 00:06:25,640 THIS CHILD AND I WAS TASKED WITH 168 00:06:25,640 --> 00:06:27,040 LETTING THE PARENTS KNOW THERE 169 00:06:27,040 --> 00:06:28,880 WERE NO OPTIONS MEDICALLY OR 170 00:06:28,880 --> 00:06:29,160 SURGICALLY. 171 00:06:29,160 --> 00:06:30,000 AND I DEPARTMENT LIKE THE 172 00:06:30,000 --> 00:06:31,080 FEELING AND I WANTED TO 173 00:06:31,080 --> 00:06:32,080 UNDERSTAND WHAT DOES IT MEAN 174 00:06:32,080 --> 00:06:34,680 WHEN A PATIENT HAS MULTIPLE 175 00:06:34,680 --> 00:06:36,040 ABDOMINAL TUMOR IMPLANTS AND WHY 176 00:06:36,040 --> 00:06:36,920 IS IT SOMETHING THAT IS 177 00:06:36,920 --> 00:06:37,720 IMPOSSIBLE TO TAKE CARE OF? 178 00:06:37,720 --> 00:06:40,600 SO WHAT I LEARNED IS THAT THIS 179 00:06:40,600 --> 00:06:42,360 INTRA DOMAININAL METASTASIS IS A 180 00:06:42,360 --> 00:06:45,000 RARE FORM OF TUMOR DISSEMINATION 181 00:06:45,000 --> 00:06:46,160 IN CHILDREN, CALLED 182 00:06:46,160 --> 00:06:47,480 SARCOMATOSEIS AND UP UNTIL I 183 00:06:47,480 --> 00:06:48,440 STARTED MANAGING THESE PATIENTS 184 00:06:48,440 --> 00:06:51,400 IT WAS REALLY THOUGHT THAT IT 185 00:06:51,400 --> 00:06:53,240 WAS IMPOSSIBLE TO REMOVE 186 00:06:53,240 --> 00:06:54,560 HUNDREDS OR THOUSANDS OF TUMORS 187 00:06:54,560 --> 00:06:57,080 IN 1 PATIENT AND RESTORE THEM TO 188 00:06:57,080 --> 00:06:57,440 HEALTH. 189 00:06:57,440 --> 00:07:00,040 AND CHILDREN WHO HAVE THIS 190 00:07:00,040 --> 00:07:02,440 DISEASE WERE BASICALLY ALWAYS 191 00:07:02,440 --> 00:07:04,680 OFFERED PALLIATIVE CARE BECAUSE 192 00:07:04,680 --> 00:07:06,640 THERE REALLY WASN'T ANY 193 00:07:06,640 --> 00:07:07,240 TREATMENT OPTIONS. 194 00:07:07,240 --> 00:07:08,520 SO I DEVELOPED A NEW APPROACH 195 00:07:08,520 --> 00:07:10,480 FOR SOME OF THESE ABDOMINAL 196 00:07:10,480 --> 00:07:12,600 CANCERS IN CHILDREN WHEN I WAS 197 00:07:12,600 --> 00:07:14,120 AT M. D. ANDERSON CANCER CENTER 198 00:07:14,120 --> 00:07:16,480 AND WHAT I LEARNED WAS THAT AN 199 00:07:16,480 --> 00:07:17,920 AGGRESSIVE SURGICAL APPROACH CAN 200 00:07:17,920 --> 00:07:19,360 BE COMPLETED AND IS WARRANTIED. 201 00:07:19,360 --> 00:07:21,760 I HAVE DONE AND REMOVED TUMORS 202 00:07:21,760 --> 00:07:24,400 AND UP TO A COUPLE THOUSAND 203 00:07:24,400 --> 00:07:26,840 TUMORS IN PATIENTS, TONIGHT. 204 00:07:26,840 --> 00:07:28,320 TAKE A LONG TIME IN THE 205 00:07:28,320 --> 00:07:29,840 OPERATING ROOM, SOMETIMES UP TO 206 00:07:29,840 --> 00:07:32,320 APPROXIMATE 20 OR 22 HOURS. 207 00:07:32,320 --> 00:07:35,040 BUT REMOVING ALL THESE LARGE MA 208 00:07:35,040 --> 00:07:37,360 LIGNABT IMPLANTS CAN RESULT IN A 209 00:07:37,360 --> 00:07:38,400 GOOD OUTCOME AND THAT'S WHAT I 210 00:07:38,400 --> 00:07:39,880 WANT TO SHARE WITH YOU TODAY. 211 00:07:39,880 --> 00:07:45,520 SO IN DEVELOPING THIS,A PROACH 212 00:07:45,520 --> 00:07:46,360 WHERE WE PROVIDE 213 00:07:46,360 --> 00:07:47,440 HYPOTHERMOGENESISSIC CHEMO 214 00:07:47,440 --> 00:07:48,720 THERAPY, I PERFORMEDLET FIRST 1 215 00:07:48,720 --> 00:07:49,560 IN 2006. 216 00:07:49,560 --> 00:07:50,600 THAT'S THE FIRST 1 DONE IN A 217 00:07:50,600 --> 00:07:52,360 CHILD IN THE WORLD. 218 00:07:52,360 --> 00:07:53,880 AND SUBSEQUENTLY HAD TO DO A 219 00:07:53,880 --> 00:07:55,320 PHASE 1 TRIAL, FOLLOWED BOO I A 220 00:07:55,320 --> 00:07:57,200 PHASE 2 TRIAL BUT IN BETWEEN 221 00:07:57,200 --> 00:08:01,320 ANALYZE THE TOXICITY SO THAT WE 222 00:08:01,320 --> 00:08:02,840 COULD UNDERSTAND MORE ABOUT HOW 223 00:08:02,840 --> 00:08:08,640 IT AFFECTED PATIENTS AND AVOID 224 00:08:08,640 --> 00:08:10,720 ANY TOXICITYS THAT MIGHT BE. 225 00:08:10,720 --> 00:08:12,520 AND THE TRIAL WAS PUBLISHED IN 226 00:08:12,520 --> 00:08:13,320 MAY OF 2018. 227 00:08:13,320 --> 00:08:14,400 SO REALLY WHAT THAT TOLD US IS 228 00:08:14,400 --> 00:08:16,400 THAT IF YOU LOOK AT THIS, WITH 229 00:08:16,400 --> 00:08:17,560 THE STUDENTS THAT PAY ATTENTION 230 00:08:17,560 --> 00:08:19,680 TO THE TIMELINE THAT IT TOOK, 231 00:08:19,680 --> 00:08:21,920 DECADES REALLY TO ESTABLISH A 232 00:08:21,920 --> 00:08:24,640 NEW TREATMENT IN A NOVEL SURGERY 233 00:08:24,640 --> 00:08:27,160 IN A YOUNG POPULATION. 234 00:08:27,160 --> 00:08:28,080 SO LET'S FIRST START OFF TALKING 235 00:08:28,080 --> 00:08:29,600 ABOUT THE PATIENTS AND WHAT THE 236 00:08:29,600 --> 00:08:30,400 PATIENTS WOULD LOOK LIKE. 237 00:08:30,400 --> 00:08:33,560 SO THIS IS A FIRST PATIENT, SO 5 238 00:08:33,560 --> 00:08:35,680 YEAR-OLD MALE, PRECEPTS WITH 239 00:08:35,680 --> 00:08:37,000 ABNORMALITIES DOLLINAL 240 00:08:37,000 --> 00:08:38,040 DISTENTION AND DISCOMFORT FOR 1 241 00:08:38,040 --> 00:08:38,960 WEEK. 242 00:08:38,960 --> 00:08:40,560 THEY PRESENT TO AN EMERGENCY 243 00:08:40,560 --> 00:08:42,680 ROOM WHERE A CT SCAN WAS 244 00:08:42,680 --> 00:08:43,800 OBTAINED AND THE PHYSICIAN ON 245 00:08:43,800 --> 00:08:46,680 CALL THOUGHT THE PATIENT HAD 246 00:08:46,680 --> 00:08:47,320 CONSTIPATION, HOWEVER, I WILL 247 00:08:47,320 --> 00:08:51,080 SHOW YOU THE SCAN WHERE THERE 248 00:08:51,080 --> 00:08:53,360 WERE MULTIPLE MASSES AND 249 00:08:53,360 --> 00:08:57,680 ASCITES, AND THE ER DOCTOR TOLD 250 00:08:57,680 --> 00:08:58,880 THE PATHWAY GIVES PARENTS THERE 251 00:08:58,880 --> 00:09:01,360 WAS NOT ANYTHING THAT COULD BE 252 00:09:01,360 --> 00:09:03,000 DONE WITH THIS NEW PROGNOSIS. 253 00:09:03,000 --> 00:09:04,640 I KNOW MANY OF YOU ARE NOT 254 00:09:04,640 --> 00:09:06,280 FAMILIAR WITH CT SCANS BUT THIS 255 00:09:06,280 --> 00:09:07,920 IS FLUID BETWEEN THE LIVER AND 256 00:09:07,920 --> 00:09:09,640 ALL THESE GRAYISH CIRCLINGS ARE 257 00:09:09,640 --> 00:09:10,760 TUMOR IMPLANTS IN THIS CROSS 258 00:09:10,760 --> 00:09:12,640 SECTION OF THE ABDOMEN. 259 00:09:12,640 --> 00:09:13,680 IF YOU LOOK OVER HERE TO THE 260 00:09:13,680 --> 00:09:16,920 RIGHT SIDE, YOU SEE THERE'S A 261 00:09:16,920 --> 00:09:18,240 LARGE AMOUNT OF FLUID, THE BOWEL 262 00:09:18,240 --> 00:09:21,560 FLOATING IN THE TUMOR AND TINY 263 00:09:21,560 --> 00:09:23,560 TINY TUMOR IMPLANTS ON THE PERO 264 00:09:23,560 --> 00:09:24,720 TON EEL SURFACE. 265 00:09:24,720 --> 00:09:26,240 NOW IN 5 YEAR-OLD BOY WAS 1 OF 266 00:09:26,240 --> 00:09:27,520 THE FIRST PATIENTS, ACTUALLY WAS 267 00:09:27,520 --> 00:09:28,600 THE FOURTH PATIENT WE TOOK ON 268 00:09:28,600 --> 00:09:30,360 OUR CLINICAL TRIAL AND WE WERE 269 00:09:30,360 --> 00:09:32,680 ABLE TO SUCCESSFULLY REMOVE ALL 270 00:09:32,680 --> 00:09:34,280 THESE HUNDREDS OF TUMORS AND 271 00:09:34,280 --> 00:09:35,560 THIS IS HIS CAT SCAN AFTER 272 00:09:35,560 --> 00:09:36,760 SURGERY AND AFTER THE PROCEDURE 273 00:09:36,760 --> 00:09:38,760 WHERE YOU CAN SEE THERE'S 274 00:09:38,760 --> 00:09:41,600 ABSOLUTELY NO TUMORS AND THAT 275 00:09:41,600 --> 00:09:43,640 THERE'S NOW FLUID NO ASCITES, 276 00:09:43,640 --> 00:09:45,240 AND HE WENT ON TO GEORGETOWN 277 00:09:45,240 --> 00:09:46,440 UNIVERSITY, I BELIEVE SHE SHOULD 278 00:09:46,440 --> 00:09:50,560 BE GRADUATING IN A YEAR OR 2. 279 00:09:50,560 --> 00:09:52,720 THIS IS ANOTHER EXAMPLE OF AN 8 280 00:09:52,720 --> 00:09:54,280 YEAR-OLD BOY, SAME TUMOR. 281 00:09:54,280 --> 00:09:55,880 WHAT I'M TRYING TO POINT OUT AND 282 00:09:55,880 --> 00:09:57,600 WHY THIS DISEASE IS SO DIFFICULT 283 00:09:57,600 --> 00:09:59,000 TO UNDERSTAND AND TREAT IS IT 284 00:09:59,000 --> 00:10:02,160 LOOKS VERY DIFFERENT IN EVERY 285 00:10:02,160 --> 00:10:04,240 SINGLE PATIENT. 286 00:10:04,240 --> 00:10:05,360 IT'S NOT LIKE COLON CANCER WHERE 287 00:10:05,360 --> 00:10:08,400 THERE'S A LUMP IN THE COLON OR 288 00:10:08,400 --> 00:10:09,400 BREAST CANCER WHERE YOU THERE'S 289 00:10:09,400 --> 00:10:11,080 1 LUMP IN THE BREAST, YOU KNOW 290 00:10:11,080 --> 00:10:12,160 WHERE IT COMES FROM, YOU PREDICT 291 00:10:12,160 --> 00:10:13,600 WHAT IT'S GOING TO DO. 292 00:10:13,600 --> 00:10:14,840 THIS TUMOR PRESENTS IN MANY 293 00:10:14,840 --> 00:10:16,200 DIFFERENT WAYS IN DIFFERENT 294 00:10:16,200 --> 00:10:18,240 PATIENTS AND HERE'S THE SAME 295 00:10:18,240 --> 00:10:19,640 DISEASE INSTEAD OF WITH MANY OF 296 00:10:19,640 --> 00:10:21,880 HUNDREDS OF STIEWMORS AND 297 00:10:21,880 --> 00:10:23,560 ASCITES, AND YOU SEE 1, 2, 3, 298 00:10:23,560 --> 00:10:25,800 AND I LABELED IT HERE AND 1, 2, 299 00:10:25,800 --> 00:10:28,160 3, OF JUST 3 LARGE TUMORS, 1 OF 300 00:10:28,160 --> 00:10:29,640 THEM BEING WEDGED PARTICULARLY 301 00:10:29,640 --> 00:10:30,400 BETWEEN THE BLADDER AND THE RUCT 302 00:10:30,400 --> 00:10:33,120 UMKC AND I WILL SHOW YOU MORE 303 00:10:33,120 --> 00:10:35,160 IMAGES OF THAT SUBSIDIARY 304 00:10:35,160 --> 00:10:35,400 QUEBTLY. 305 00:10:35,400 --> 00:10:37,160 SO ANOTHER EXAMPLE OF A 13 306 00:10:37,160 --> 00:10:38,360 YEAR-OLD MALE WHO WAS IN A 307 00:10:38,360 --> 00:10:40,320 SURFING ACCIDENT AND THOUGHT 308 00:10:40,320 --> 00:10:44,120 THAT HIS ABDOMINAL PAIN WAS FROM 309 00:10:44,120 --> 00:10:44,960 SURFING. 310 00:10:44,960 --> 00:10:48,400 HE HAD ABDOMINAL DISTENTION, NO 311 00:10:48,400 --> 00:10:52,240 FATIGUE, NO VOMITING, NO FEVER, 312 00:10:52,240 --> 00:10:53,560 NO CONS TIARASIPATION OR 313 00:10:53,560 --> 00:10:55,040 DIARRHEA, HE HAD A CT SCAN AND 314 00:10:55,040 --> 00:10:56,640 AGAIN IT LOOKS VERY DIFFERENT. 315 00:10:56,640 --> 00:10:57,680 WE HAVE THE LIVER FLOATING IN 316 00:10:57,680 --> 00:10:59,480 THE MIDDLE OF THE 317 00:10:59,480 --> 00:11:00,880 ASCITEXPECTATIONS S, ABOUT YOU A 318 00:11:00,880 --> 00:11:02,480 THICKENED AREA IN THE TUMOR OF 319 00:11:02,480 --> 00:11:03,000 THE RIGHT DIAPHRAGM. 320 00:11:03,000 --> 00:11:05,480 AND I WILL SHOW YOU ISHT 321 00:11:05,480 --> 00:11:07,480 OPERATIVE IMAGES OF THIS 322 00:11:07,480 --> 00:11:07,720 SHORTLY. 323 00:11:07,720 --> 00:11:09,920 AND IN ADDITION TO BEING INTRA 324 00:11:09,920 --> 00:11:11,320 ABDOMINAL, AND PERO TON EEL AS 325 00:11:11,320 --> 00:11:12,640 WELL, SO AGAIN A CONFUSING 326 00:11:12,640 --> 00:11:15,120 PICTURE OF HOW TO UNDERSTAND 327 00:11:15,120 --> 00:11:17,400 THIS DISEASE. 328 00:11:17,400 --> 00:11:18,000 HERE'S A 22 YEAR-OLD. 329 00:11:18,000 --> 00:11:21,000 THIS PATIENT HAS NO FLUID, NO 330 00:11:21,000 --> 00:11:22,440 ASCITES, AND HERE'S THE LIVER, 331 00:11:22,440 --> 00:11:24,640 THIS IS THE RIGHT DIAPHRAGM AND 332 00:11:24,640 --> 00:11:27,040 THE GRAYISH AREA IS TUMOR ON THE 333 00:11:27,040 --> 00:11:27,880 RIGHT DIAFRAM. 334 00:11:27,880 --> 00:11:29,680 WHEN YOU LOOK IN THE PELVIS, YOU 335 00:11:29,680 --> 00:11:31,480 SEE THIS TUMOR WEDGED BETWEEN 336 00:11:31,480 --> 00:11:33,520 THE BLADDER AND THE RECTUM AND 337 00:11:33,520 --> 00:11:35,080 THE WAY I WAS TOUT IN RESIDENCY 338 00:11:35,080 --> 00:11:36,560 WAS WHEN YOU HAVE A PATIENT 339 00:11:36,560 --> 00:11:38,320 WHERE YOU CAN'T IDENTIFY A SPACE 340 00:11:38,320 --> 00:11:39,520 BETWEEN THE ORGANS AND THE ORGAN 341 00:11:39,520 --> 00:11:43,080 HAS TO BE REMOVED IN ORDER TO 342 00:11:43,080 --> 00:11:44,800 GET NEGATIVE MARGINS AND BE ABLE 343 00:11:44,800 --> 00:11:47,200 TO PROVIDE THE PATIENT WITH GOOD 344 00:11:47,200 --> 00:11:48,160 LONG-TERM OUTCOME. 345 00:11:48,160 --> 00:11:49,600 IN FACT, IN THIS PATIENT AND IN 346 00:11:49,600 --> 00:11:50,880 MANY OTHERS I SEE WITH THIS 347 00:11:50,880 --> 00:11:53,280 DISEASE, I WAS ABLE TO TAKE THIS 348 00:11:53,280 --> 00:11:56,280 TUMOR OUT IN THE RECTUM AND 349 00:11:56,280 --> 00:11:57,040 BRADDER REMAIN INTACT, THAT'S 350 00:11:57,040 --> 00:11:58,880 PART OF THE TECHNIQUE I HAD TO 351 00:11:58,880 --> 00:12:05,280 TEACH MYSELF OVER THE YEARS. 352 00:12:05,280 --> 00:12:07,720 HERE'S ANOTHER REASON THIS IS SO 353 00:12:07,720 --> 00:12:09,720 DIFFICULT, HERE'S A RADIOLOGIST 354 00:12:09,720 --> 00:12:10,920 IMPRESSION OF A CT SCAN, THEY 355 00:12:10,920 --> 00:12:12,320 ARE POINTING OUT THE NUMBER OF 356 00:12:12,320 --> 00:12:14,080 LESIONS THEY SEE, THE SIZE OF 357 00:12:14,080 --> 00:12:15,960 THE LESIONS AND WHAT THEY 358 00:12:15,960 --> 00:12:16,640 ACTUALLY--WHAT I ACTUALLY FOUND 359 00:12:16,640 --> 00:12:19,080 WHEN I WENT TO SURGERY WAS MUCH 360 00:12:19,080 --> 00:12:22,000 MORE THAN THAT, OF ALMOST 3000 361 00:12:22,000 --> 00:12:24,440 TUMORS IT TOOK ME 17 HOURS, NO 362 00:12:24,440 --> 00:12:26,840 FAULT OF THE THE RADIOLOGIST, 363 00:12:26,840 --> 00:12:28,600 THIS IS JUST A VERY EVASIVE 364 00:12:28,600 --> 00:12:29,160 DISEASE. 365 00:12:29,160 --> 00:12:31,240 AND THE NEXT IRMPAGS WILL BE 366 00:12:31,240 --> 00:12:33,240 INTEROPERATIVE IMAGES AND THIS 367 00:12:33,240 --> 00:12:36,680 IS THAT SAME PATIENT, THE 368 00:12:36,680 --> 00:12:38,280 SPLEEN, THE DISTAL PANCREAS AND 369 00:12:38,280 --> 00:12:39,320 THE [INDISCERNIBLE], ALL THOSE 370 00:12:39,320 --> 00:12:40,880 WHITE SPOTS ARE TUMORS, AGAIN 371 00:12:40,880 --> 00:12:42,880 IT'S A SLICER VIEW OF THE SAME 372 00:12:42,880 --> 00:12:45,280 THING, WITH THE MEASUREMENT TAPE 373 00:12:45,280 --> 00:12:46,800 OF ABOUT 15-CENTIMETERS FOR 374 00:12:46,800 --> 00:12:49,560 CONTEXT AND MULTIPLE, MULTIPLE 375 00:12:49,560 --> 00:12:54,160 TUMORS, TOO NUMEROUS TO COUNT IN 376 00:12:54,160 --> 00:12:55,080 THIS IMAGE. 377 00:12:55,080 --> 00:12:56,360 HERE'S ANOTHER IMAGE OF THE 378 00:12:56,360 --> 00:12:58,080 PATIENT WITH THE SAME DISEASE, 379 00:12:58,080 --> 00:13:00,960 WE ARE LOOKING DOWN INTO THE 380 00:13:00,960 --> 00:13:02,000 PELVIC CAVITY, THE PATIENTS FEET 381 00:13:02,000 --> 00:13:03,320 ARE AT THE TOP OF THE SCREEN, 382 00:13:03,320 --> 00:13:05,520 HEAD IS AT THE BOTTOM, THIS IS 383 00:13:05,520 --> 00:13:08,000 LEFT, THIS IS RIGHT AND INCISION 384 00:13:08,000 --> 00:13:10,360 IS DOWN THE LEFT OF THE ABDOMEN, 385 00:13:10,360 --> 00:13:12,960 MY HAND IS ON THE COLON AND 386 00:13:12,960 --> 00:13:14,480 RECTUM AND THE SMALL TUMOR 387 00:13:14,480 --> 00:13:15,760 NODULES HERE ARE THE DISEASE AND 388 00:13:15,760 --> 00:13:17,320 YOU SEE THEY ARE WHITE IN COLOR 389 00:13:17,320 --> 00:13:18,520 WHICH IS IMPORTANT TO RECOGNIZE 390 00:13:18,520 --> 00:13:20,800 IS THAT MEANS THAT THEY HAVE 391 00:13:20,800 --> 00:13:22,480 VERY LITTLE ANGIOGENESIS, THEY 392 00:13:22,480 --> 00:13:24,200 HAVE VERY--THE TUMORS ARE NOT 393 00:13:24,200 --> 00:13:25,640 MAKING THEIR OWN BLOOD VESSELS 394 00:13:25,640 --> 00:13:27,160 AS WELL SO THEY WILL USUALLY 395 00:13:27,160 --> 00:13:29,160 STOP GROWING AND I WILL SHOW YOU 396 00:13:29,160 --> 00:13:30,400 LATER ABOUT WHY THIS IS 397 00:13:30,400 --> 00:13:30,880 IMPORTANT. 398 00:13:30,880 --> 00:13:31,800 THIS PATIENT RECEIVED CHEMO 399 00:13:31,800 --> 00:13:33,760 THERAPY AND THEREFORE THE TUMORS 400 00:13:33,760 --> 00:13:36,440 ARE THESE WHITE COLOR BUT IF YOU 401 00:13:36,440 --> 00:13:37,080 LOOK CAREFULLY, ESPECIALLY THOSE 402 00:13:37,080 --> 00:13:38,640 OF YOU ON A SCREEN THAT YOU CAN 403 00:13:38,640 --> 00:13:40,240 GET CLOSER TO, THERE'S A TUMOR 404 00:13:40,240 --> 00:13:41,640 NODULE HERE AND HERE AND HERE, 405 00:13:41,640 --> 00:13:43,680 ALL OF THESE ARE TUMOR NODULES, 406 00:13:43,680 --> 00:13:46,160 OWL OF THESE HERE ARE TUMOR 407 00:13:46,160 --> 00:13:48,360 NODULES AS WELL AS HERE AND IF 408 00:13:48,360 --> 00:13:50,120 YOU LOOK CLOSELY THERE'S A TINY 409 00:13:50,120 --> 00:13:51,960 TINY WHITE DOT, SO JUST IN THE 410 00:13:51,960 --> 00:13:53,760 IMAGE IT'S PROBABLY ABOUT 40 411 00:13:53,760 --> 00:13:54,720 TUMORS. 412 00:13:54,720 --> 00:13:57,240 NOW WE'RE LOOKING UP INTO A 413 00:13:57,240 --> 00:13:58,080 DIFFERENT PATIENT ON THE RIGHT 414 00:13:58,080 --> 00:14:00,240 UPPER AREA OF THE ABDOMINAL 415 00:14:00,240 --> 00:14:00,480 CAVITY. 416 00:14:00,480 --> 00:14:01,600 SO THE HEAD OF THE PATIENT IS TO 417 00:14:01,600 --> 00:14:06,400 THE RIGHT, THE FEET ARE TO YOUR 418 00:14:06,400 --> 00:14:06,600 LEFT. 419 00:14:06,600 --> 00:14:08,200 THE LIVER IS UP TO THE RIGHT. 420 00:14:08,200 --> 00:14:09,400 THIS IS THE DIAPHRAGM. 421 00:14:09,400 --> 00:14:10,640 THIS IS PAISKLY HOW THE INITIAL 422 00:14:10,640 --> 00:14:11,960 PATIENT THAT I SAW LOOKED WHEN 423 00:14:11,960 --> 00:14:12,960 WE SAID THERE WAS NOTHING THAT 424 00:14:12,960 --> 00:14:15,400 COULD BE DONE AND THAT'S BECAUSE 425 00:14:15,400 --> 00:14:16,680 WE'RE TAUGHT WHEN YOU SEE THIS 426 00:14:16,680 --> 00:14:18,280 MUCH DISEASE ON AN ORGAN THAT 427 00:14:18,280 --> 00:14:19,720 THE ENTIRE ORGAN NEEDS TO BE 428 00:14:19,720 --> 00:14:21,160 REMOVED AND I WILL SHOW YOU HOW 429 00:14:21,160 --> 00:14:24,080 I REMOVE THIS TUMOR WITHOUT 430 00:14:24,080 --> 00:14:24,960 REMOVING THE DIAPHRAGM. 431 00:14:24,960 --> 00:14:27,960 THIS IS ANOTHER IMAGE OF OF THE 432 00:14:27,960 --> 00:14:32,160 SMALL BOWEL, THIS INSTRUMENT, 433 00:14:32,160 --> 00:14:36,160 THIS FORCEP IS ABOUT 3-INCHES IN 434 00:14:36,160 --> 00:14:37,800 DIAMETER AND YOU CAN SEE HOW 435 00:14:37,800 --> 00:14:38,720 SMALL THESE TUMORS ARE. 436 00:14:38,720 --> 00:14:41,480 YOU CAN SEE THREAR IN THE SMALL 437 00:14:41,480 --> 00:14:43,400 INTESTINE AND THESE ARE PURPLE 438 00:14:43,400 --> 00:14:47,280 IN COLOR BECAUSE I LIFTED UP THE 439 00:14:47,280 --> 00:14:48,480 PERITONEUM AND REMOVED THE BLOOD 440 00:14:48,480 --> 00:14:50,000 SUPPLY AND THAT'S WHY IT'S THE 441 00:14:50,000 --> 00:14:51,360 PURPLE COLOR AND IN THIS 442 00:14:51,360 --> 00:14:53,680 PARTICULAR PATIENT I REMOVED THE 443 00:14:53,680 --> 00:14:55,720 NODULES WITHOUT REMOVING THE 444 00:14:55,720 --> 00:14:56,280 INTESTINE. 445 00:14:56,280 --> 00:14:59,960 THIS IS AN IMAGE OF THE OMENTA, 446 00:14:59,960 --> 00:15:01,480 THE FATTY DRAPE THAT COVERS THE 447 00:15:01,480 --> 00:15:03,000 BOWEL AND YOU CAN SEE SMALL 448 00:15:03,000 --> 00:15:04,720 WHITE DOTS AND TUMORS IN THAT AS 449 00:15:04,720 --> 00:15:04,920 WELL. 450 00:15:04,920 --> 00:15:06,200 SO BACK TO THE PATIENT, I WAS 451 00:15:06,200 --> 00:15:10,880 SHOWING YOU WITH A TUMOROT 452 00:15:10,880 --> 00:15:11,160 DIAPHRAGM. 453 00:15:11,160 --> 00:15:12,400 THE HEAD IS TO YOUR RIGHT, FEET 454 00:15:12,400 --> 00:15:13,600 ARE ON THE LEFT. 455 00:15:13,600 --> 00:15:15,480 THIS IS THE BELLY BUTTON, THE 456 00:15:15,480 --> 00:15:17,560 INCISION IS RIGHT DOWN THE 457 00:15:17,560 --> 00:15:18,680 MIDDLE, THESE RETRACT TRACTORS 458 00:15:18,680 --> 00:15:20,040 ARE HOLDING UP THE ABDOMINAL 459 00:15:20,040 --> 00:15:21,760 WALL SO I CAN SEE A BIT BETTER, 460 00:15:21,760 --> 00:15:23,520 THIS IS THE LIVER SO IF YOU LOOK 461 00:15:23,520 --> 00:15:24,960 CAREFULLY HERE, THIS IS THE 462 00:15:24,960 --> 00:15:26,480 TENDON OF THE DIAPHRAGM, THIS IS 463 00:15:26,480 --> 00:15:27,760 DIAPHRAGM MUSCLE, AND I'M 464 00:15:27,760 --> 00:15:30,400 DISSECTING IT OFF OF THIS AREA. 465 00:15:30,400 --> 00:15:33,000 YOU CAN SEE THAT THERE'S--TUMOR 466 00:15:33,000 --> 00:15:36,400 NODULES ARE ALL IN THE SHEET OF 467 00:15:36,400 --> 00:15:37,840 PERITONEUM AND THE DIAPHRAGM IS 468 00:15:37,840 --> 00:15:39,480 INTACT, SO AT THE END OF THAT, 469 00:15:39,480 --> 00:15:44,640 YOU HAVE A SHEET OF TUMORS ON 470 00:15:44,640 --> 00:15:51,640 THE PERITONEUM. 471 00:15:51,640 --> 00:15:54,760 AND YOU CAN SEE I REMOVED THE 472 00:15:54,760 --> 00:15:55,880 TUMOR WITHOUT REMOVING THE 473 00:15:55,880 --> 00:15:56,480 BLADDER AND RECTUM. 474 00:15:56,480 --> 00:15:58,640 SO THIS IS THE LARGE TUMOR MASS, 475 00:15:58,640 --> 00:16:01,520 THIS IS THE THIN LAYER OF 476 00:16:01,520 --> 00:16:03,040 PERITONEUM, AND YOU CAN SEE THE 477 00:16:03,040 --> 00:16:05,400 GREEN TOWEL THROUGH THIS VERY 478 00:16:05,400 --> 00:16:07,920 THIN LAYER AND THE PERITONEUM, 479 00:16:07,920 --> 00:16:10,160 THAT COVERS ALL OF THE ORGANS IN 480 00:16:10,160 --> 00:16:12,360 THE ABDOMINAL CAVITY AND GOD IT 481 00:16:12,360 --> 00:16:13,560 THERE TO KEEP THE ORGANS FROM 482 00:16:13,560 --> 00:16:17,320 TICKING TOGETHER SO THAT YOUR 483 00:16:17,320 --> 00:16:19,480 BLADDER DOESN'T TICK TO YOUR 484 00:16:19,480 --> 00:16:23,040 RECTUM, THE LIVER DOESN'T STICK 485 00:16:23,040 --> 00:16:24,080 TO THE STOMACH, ET CETERA, AND 486 00:16:24,080 --> 00:16:25,560 FOR REASONS I'M TRYING TO LEARN, 487 00:16:25,560 --> 00:16:27,000 IT SITS ON TOP, IT DOES NOT 488 00:16:27,000 --> 00:16:28,960 INVADE INTO THE ORGANS AND'S WHY 489 00:16:28,960 --> 00:16:32,240 WE'RE ABLE TO REMOVE THIS WHOLE 490 00:16:32,240 --> 00:16:33,840 PERITONEUM, THIS WAS ON THE 491 00:16:33,840 --> 00:16:35,120 BLADDER AND THIS IS RIGHT AND 492 00:16:35,120 --> 00:16:37,560 LEFT AND LEAVE THE MAJOR ORGANS 493 00:16:37,560 --> 00:16:39,000 IN INTACT AND WHAT THAT LOOKS 494 00:16:39,000 --> 00:16:40,720 LIKE AFTER THE RESECTION IN THE 495 00:16:40,720 --> 00:16:41,880 PATIENT, AGAIN THIS PATIENT'S 496 00:16:41,880 --> 00:16:44,640 FEET ARE AT THE TOP OF YOUR 497 00:16:44,640 --> 00:16:46,160 SCREEN, HEADS AT THE BOTTOM OF 498 00:16:46,160 --> 00:16:48,520 THE SCREEN, THIS CLAMP IS ON THE 499 00:16:48,520 --> 00:16:51,440 BLADDER AND THE FORCEPS HERE IS 500 00:16:51,440 --> 00:16:53,600 POINTING TO THIS IN THE MALE 501 00:16:53,600 --> 00:16:54,400 PATIENT, THIS IS VERY IMPORTANT 502 00:16:54,400 --> 00:16:56,080 LATER ON WHEN I TALK ABOUT 503 00:16:56,080 --> 00:16:57,920 SCIENTIFICALLY HOW I FIGURED OUT 504 00:16:57,920 --> 00:16:59,440 WHERE THIS TUMOR COMES FROM AND 505 00:16:59,440 --> 00:17:00,200 HOW IT GROWS. 506 00:17:00,200 --> 00:17:01,960 THIS IS THE SURFACE OF THE 507 00:17:01,960 --> 00:17:05,480 RECTUM HERE, THIS IS THE RIGHT 508 00:17:05,480 --> 00:17:07,280 VAS, DEFERENCE, AND THE GOING TO 509 00:17:07,280 --> 00:17:10,440 THE RIGHT AND LEFT TESTICLE AND 510 00:17:10,440 --> 00:17:12,920 SOME VASCULATURE INTERNAL ILIAT 511 00:17:12,920 --> 00:17:13,160 ARTERIES. 512 00:17:13,160 --> 00:17:14,920 SO THIS OBSERVATION THAT PRETTY 513 00:17:14,920 --> 00:17:17,400 MUCH FOR EVERYBODY PATIENT I WAS 514 00:17:17,400 --> 00:17:19,600 CUTTING TUMOR OFF THESE SEMINOLE 515 00:17:19,600 --> 00:17:21,640 VESICLES LED TO A DISCOVERY I 516 00:17:21,640 --> 00:17:22,800 WILL TELL YOU ABOUT LATER. 517 00:17:22,800 --> 00:17:26,000 SO ALL THE IMAGES HAVE BEEN A 518 00:17:26,000 --> 00:17:28,000 DIAGNOSIS OF DESMODEL CITIZEN 519 00:17:28,000 --> 00:17:29,040 PLASTIC SMALL TUMOR AND THIS IS 520 00:17:29,040 --> 00:17:32,640 WE DON'T KNOW THE TUMOR OF 521 00:17:32,640 --> 00:17:33,640 ORINIGEIN. 522 00:17:33,640 --> 00:17:34,840 IT'S QUITE RARE, THERE MIGHT BE 523 00:17:34,840 --> 00:17:36,480 200 CASES IN THE UNITED STATES. 524 00:17:36,480 --> 00:17:38,440 MOST PATIENTS ARE MALE AND THE 525 00:17:38,440 --> 00:17:40,720 MEDIAN AGE IS ABOUT 18 RANGING 526 00:17:40,720 --> 00:17:48,600 FROM ABOUT 5-25 YEARS OLD, MOST 527 00:17:48,600 --> 00:17:52,680 COMMONLY. 528 00:17:52,680 --> 00:17:54,800 THE PRESENTING--VERY, VERY POOR, 529 00:17:54,800 --> 00:17:56,400 THEY MAY BE 10 OR 15% OF THE 530 00:17:56,400 --> 00:17:58,480 PATIENTS WERE SURVIVING LONGER 531 00:17:58,480 --> 00:18:02,600 THAN 5 YEARS AND THIS WAS 532 00:18:02,600 --> 00:18:06,200 DESPITE AGGRESSIVE CHEMO 533 00:18:06,200 --> 00:18:08,360 THERAPY, RADIATION THERAPY DONE 534 00:18:08,360 --> 00:18:09,400 BY MY PREVIOUS COLLEAGUES. 535 00:18:09,400 --> 00:18:12,160 INTERESTING THING IS THAT THIS 536 00:18:12,160 --> 00:18:13,800 NEVER PRESENTS WITH 1 KIND. 537 00:18:13,800 --> 00:18:14,680 EVERY PATIENT HAS METASTASIS, 538 00:18:14,680 --> 00:18:16,520 WHICH IS A MISNOMER IN THIS 539 00:18:16,520 --> 00:18:17,800 PARTICULAR CASE, BUT ALL OF THE 540 00:18:17,800 --> 00:18:19,200 PEASHTS HAVE MORE THAN 1 TUMOR 541 00:18:19,200 --> 00:18:22,800 AT THE TIME OF DIAGNOSIS. 542 00:18:22,800 --> 00:18:25,440 IT'S A VERY YOUNG TUMOR FIRST 543 00:18:25,440 --> 00:18:27,520 DESCRIBED BY [INDISCERNIBLE] 544 00:18:27,520 --> 00:18:28,960 FROM 1989 FROM MEMORIAL SLOAN 545 00:18:28,960 --> 00:18:30,200 KETTERRING CANCER CENTER AND IT 546 00:18:30,200 --> 00:18:33,640 HAS A FUSION PROTEIN THAT'S VERY 547 00:18:33,640 --> 00:18:34,680 CHARACTERISTIC, A TRANSLOCATION 548 00:18:34,680 --> 00:18:37,640 BETWEEN THE 11th AND 13th 549 00:18:37,640 --> 00:18:41,440 CHROMOSOME RESULTING IN A EWING 550 00:18:41,440 --> 00:18:44,040 SARCOMA AND WILM'S TUMOR FUSION 551 00:18:44,040 --> 00:18:46,520 PROTEIN SO BIOLOGICALLY THE 552 00:18:46,520 --> 00:18:50,320 TUMOR BEHAVES LIKE A EWING SORRY 553 00:18:50,320 --> 00:18:52,760 COMA AND A WILM'S TUMOR, AND 554 00:18:52,760 --> 00:18:55,120 THIS IS THE TUMOR IN EVERY CASE. 555 00:18:55,120 --> 00:18:58,120 AND EVERY TIME WE KNOW IS THAT 556 00:18:58,120 --> 00:18:59,720 THE CHROMOSOME 22 TRANSLOCATES 557 00:18:59,720 --> 00:19:02,000 TO 11 AND YOU GET A FUSION GENE 558 00:19:02,000 --> 00:19:07,600 BUT WE DON'T KNOW HOW THE DSRCT 559 00:19:07,600 --> 00:19:09,360 DEVELOPING AFTER THIS POINT. 560 00:19:09,360 --> 00:19:13,240 WE THINK IT PROBABLY ARRIVES 561 00:19:13,240 --> 00:19:15,640 FROM THE MESOTHELIOMA EPITHELIAL 562 00:19:15,640 --> 00:19:16,480 CELLS AND DIFFERENTIATION 563 00:19:16,480 --> 00:19:18,400 BECAUSE IT'S IN THE PERITONEUM 564 00:19:18,400 --> 00:19:19,840 AND THE PLURIPOTENT CELLSA. 565 00:19:19,840 --> 00:19:24,280 THE ORIGIN WE THINK ARE FROM 566 00:19:24,280 --> 00:19:25,200 HIGHLY UNDIFFERENTIATED 567 00:19:25,200 --> 00:19:25,840 MESSENTERIEN CHIMMAL CELLS AND 568 00:19:25,840 --> 00:19:27,760 THAT'S BECAUSE WE SEE IT IN LATE 569 00:19:27,760 --> 00:19:29,400 STAGES IN THE BONE AND BRAIN. 570 00:19:29,400 --> 00:19:32,920 AS I SHOWED YOU THE TUMORS ARE 571 00:19:32,920 --> 00:19:35,160 SOLID AND FIRM, THE YELLOWISH 572 00:19:35,160 --> 00:19:36,680 GRAY SURFACE RESULTS AFTER CHEMO 573 00:19:36,680 --> 00:19:40,040 THERAPY, PRIOR TO CHEMO THERAPY, 574 00:19:40,040 --> 00:19:40,800 THEY'RE VERY HEMORRHAGIC AND 575 00:19:40,800 --> 00:19:42,760 NECROTIC AND THEY CAN BE SMALL 576 00:19:42,760 --> 00:19:43,240 AND LARGE. 577 00:19:43,240 --> 00:19:45,640 THIS IS A BIOPSY I TOOK FROM 1 578 00:19:45,640 --> 00:19:47,840 OF MY PATIENTS IN THE 579 00:19:47,840 --> 00:19:48,640 [INDISCERNIBLE] TO SHOW THE 580 00:19:48,640 --> 00:19:50,080 REASON THE TUMOR HAS THIS NAME 581 00:19:50,080 --> 00:19:54,720 AND WHY IT'S SO CHALLENGING TO 582 00:19:54,720 --> 00:19:55,200 TREAT AND UNDERSTAND. 583 00:19:55,200 --> 00:19:58,520 YOU CAN SEE HERE A HIGH POWER, 584 00:19:58,520 --> 00:20:00,520 THIS IS UCD SMALL ROUND BLUE 585 00:20:00,520 --> 00:20:01,600 CELLS WHICH ARE MITOTICALLY 586 00:20:01,600 --> 00:20:02,880 ACTIVE IN DIVIDING CELLS AND 587 00:20:02,880 --> 00:20:05,560 THEN YOU SEE THESE LIGHTER 588 00:20:05,560 --> 00:20:08,280 COLORED STROMAL COMPONENT THAT'S 589 00:20:08,280 --> 00:20:09,240 FIBROTIC, IT'S NOT VERY 590 00:20:09,240 --> 00:20:10,200 CELLULAR, THERE ARE NO CELLS 591 00:20:10,200 --> 00:20:12,080 THAT ARE DIVIDING AND IT LOOKS 592 00:20:12,080 --> 00:20:13,480 VERY QUIET SO TO SPEAK. 593 00:20:13,480 --> 00:20:15,240 NOW THIS SMALL ROUND BLUE CELL 594 00:20:15,240 --> 00:20:16,800 COMPONENT THAT IS RAPIDLY 595 00:20:16,800 --> 00:20:20,360 DIVIDING ARE THE CELLS THAT ARE 596 00:20:20,360 --> 00:20:21,640 TARGETED BY CYTOTOXIC CHEMO 597 00:20:21,640 --> 00:20:22,040 THERAPY. 598 00:20:22,040 --> 00:20:23,600 SO WHEN THE CHEMO THERAPY IS 599 00:20:23,600 --> 00:20:25,080 GIVEN PRIOR TO SURGERY, THESE 600 00:20:25,080 --> 00:20:28,920 CELLS DIE BECAUSE OF THE CHEMO 601 00:20:28,920 --> 00:20:31,120 THERAPY ABOUT THESE FIBROTIC 602 00:20:31,120 --> 00:20:32,600 BANDS IN BETWEEN 2 NOT IS THAT'S 603 00:20:32,600 --> 00:20:34,240 WHY THE TUMORS HAVE THE WHITE 604 00:20:34,240 --> 00:20:35,320 COLOR I SHOWED YOU BEFORE AND 605 00:20:35,320 --> 00:20:37,960 THAT'S WHAT LEFT FOR THE SURGEON 606 00:20:37,960 --> 00:20:39,840 TO RESECT BACK AFTER THE CHEMO 607 00:20:39,840 --> 00:20:41,680 THERAPY HAS KILLED THESE SMALL 608 00:20:41,680 --> 00:20:43,560 ROUND BLUE CELLS BETTER IN 609 00:20:43,560 --> 00:20:43,800 MITOSIS. 610 00:20:43,800 --> 00:20:45,640 SO THIS IS A SPECIMEN FROM A 611 00:20:45,640 --> 00:20:47,960 PATIENT OF MINE AFTER CHEMO 612 00:20:47,960 --> 00:20:48,720 THERAPY. 613 00:20:48,720 --> 00:20:52,000 SO YOU CAN SEE THIS TUMOR IS 614 00:20:52,000 --> 00:20:52,840 MAYBE ABOUT 2-3-MILLIMETERS BUT 615 00:20:52,840 --> 00:20:54,920 LOOKING AT HIGH POWERED 1 FROM 4 616 00:20:54,920 --> 00:20:58,680 X TO 4 D X, YOU SEE THAT THERE'S 617 00:20:58,680 --> 00:21:00,440 A VERY SMALL NEST OF THESE ROUND 618 00:21:00,440 --> 00:21:01,840 BLUE CELLS AND THE LARGE 619 00:21:01,840 --> 00:21:03,240 COMPONENT OF THIS FIBROUS 620 00:21:03,240 --> 00:21:04,200 STRANDS THAT HAVE NO CELLS IN 621 00:21:04,200 --> 00:21:07,000 THEM AND THIS IS A RESULT OF 622 00:21:07,000 --> 00:21:08,120 EFFECTIVE CHEMO THERAPY REDUCING 623 00:21:08,120 --> 00:21:11,960 THOSE DIVIDING CELLS TO VERY 624 00:21:11,960 --> 00:21:12,200 MINIMAL. 625 00:21:12,200 --> 00:21:15,240 THIS IS ANOTHER TUMOR IMPLANT IN 626 00:21:15,240 --> 00:21:15,600 THE PERITONEUM. 627 00:21:15,600 --> 00:21:16,280 AND YOU SLEEP APNEA AND OBESITYY 628 00:21:16,280 --> 00:21:19,200 IT ON EITHER SIDE. 629 00:21:19,200 --> 00:21:21,520 --YOU SEE IT ON EITHER SIDE. 630 00:21:21,520 --> 00:21:23,000 I WAS SURPRISED FIRST TIME I SAW 631 00:21:23,000 --> 00:21:24,560 THIS FROM A PATIENT I REMOVED 632 00:21:24,560 --> 00:21:25,960 THE TUMOR FROM IS THIS THESE 633 00:21:25,960 --> 00:21:27,680 CELLS NEXT TO THE TUMOR THAT 634 00:21:27,680 --> 00:21:28,800 ACTUALLY IS TUMOR IN THERE AS 635 00:21:28,800 --> 00:21:31,240 WELL, SO IF YOU LOOK AT THE 636 00:21:31,240 --> 00:21:33,320 PERITONEUM HERE, YOU SEE THERE'S 637 00:21:33,320 --> 00:21:36,840 ACTUALLY TUMOR ADJACENT TO THE 638 00:21:36,840 --> 00:21:37,800 PERITONEUM NODULE WHICH IS WHAT 639 00:21:37,800 --> 00:21:40,120 MAKES MOOY TAKE OUT A WIDER 640 00:21:40,120 --> 00:21:41,400 PIECE WHEN I DO SURGERY, NOW 641 00:21:41,400 --> 00:21:42,720 THESE OF COURSE I COULD NOTE SEE 642 00:21:42,720 --> 00:21:44,560 WITH MY EYES AND I WANTED TO 643 00:21:44,560 --> 00:21:46,000 KNOW EVEN MORE ABOUT WHAT I 644 00:21:46,000 --> 00:21:47,640 COULDN'T SEE WITH MY EYES. 645 00:21:47,640 --> 00:21:49,960 SO I REMOVED THIS PIECE OF 646 00:21:49,960 --> 00:21:51,200 PERITONEUM AND VERY 647 00:21:51,200 --> 00:21:55,360 INTERESTINGLY WHAT YOU FIND AND 648 00:21:55,360 --> 00:22:05,080 GROWINGSLY AND WHEN YOU LOOK THE 649 00:22:05,080 --> 00:22:06,840 TUMOR HERE WHERE YOU SEE THE 650 00:22:06,840 --> 00:22:08,080 SMALLER IN BLUE AND DIVIDING 651 00:22:08,080 --> 00:22:09,280 CELLS AND IMMUNE CELLS IN THERE 652 00:22:09,280 --> 00:22:09,720 AS WELL. 653 00:22:09,720 --> 00:22:10,760 SO HERE'S THE PROBLEM. 654 00:22:10,760 --> 00:22:12,560 IF I AS A SURGEON GO IN AND 655 00:22:12,560 --> 00:22:14,680 REMOVE ALL THESE TUMORS AND I 656 00:22:14,680 --> 00:22:15,960 CAN'T SEE THESE MICROSCOPIC 657 00:22:15,960 --> 00:22:17,280 CELLS, OBVIOUSLY THE TUMOR COULD 658 00:22:17,280 --> 00:22:20,400 GROW BACK. 659 00:22:20,400 --> 00:22:22,040 SO, WHAT THE HYPER 660 00:22:22,040 --> 00:22:22,760 THERMOGENESISSIC CHEMO THERAPY 661 00:22:22,760 --> 00:22:25,200 DOES IS PENETRATE THIS VERY THIN 662 00:22:25,200 --> 00:22:27,640 LAYER OF PERITONEUM WHERE WE 663 00:22:27,640 --> 00:22:29,640 DON'T SEE ANY GROSS TUMOR AND 664 00:22:29,640 --> 00:22:31,400 KILLS THOSE MICROSCOPIC CELLS SO 665 00:22:31,400 --> 00:22:33,600 THAT THE TUMOR DOES NOT REGROW. 666 00:22:33,600 --> 00:22:35,360 SO THE WAY THE HYPER 667 00:22:35,360 --> 00:22:36,320 THERMOGENESISSIC CHEMO THERAPY 668 00:22:36,320 --> 00:22:38,080 WORKS THIS IS JUST A CARTOON 669 00:22:38,080 --> 00:22:39,800 DIAGRAM AND ALL THE EQUIPMENT 670 00:22:39,800 --> 00:22:40,520 LOOKS DIFFERENT FROM DIFFERENT 671 00:22:40,520 --> 00:22:42,480 COMPANIES BUT THE CONCEPT IS 672 00:22:42,480 --> 00:22:45,560 THAT THE PATIENT IS LYING IN THE 673 00:22:45,560 --> 00:22:46,880 OPERATING ROOM, AN INCISION MADE 674 00:22:46,880 --> 00:22:48,280 DOWN THE MIDDLE, THE SURGERY IS 675 00:22:48,280 --> 00:22:50,560 DONE AS WE REMOVE THE TUMORS AS 676 00:22:50,560 --> 00:22:51,880 I PREVIOUSLY SHOWED YOU AND THE 677 00:22:51,880 --> 00:22:54,480 CHEMO THERAPY DRUG IS 678 00:22:54,480 --> 00:22:55,640 INFISCHERRED INTO THIS TUBE, 679 00:22:55,640 --> 00:22:59,320 COMES OUT OF THE OTHER TUBE, THE 680 00:22:59,320 --> 00:23:00,960 ABDOMEN DISTENDS WITH FLUID. 681 00:23:00,960 --> 00:23:03,360 YOU GENTLY PRESS ON THE 682 00:23:03,360 --> 00:23:05,360 ABDOMINAL WALL TO AGITATE THE 683 00:23:05,360 --> 00:23:07,440 FLUID SO IT EVENLY CIRCULES IN 684 00:23:07,440 --> 00:23:08,760 THE CAVITY AND THERE'S A 685 00:23:08,760 --> 00:23:10,080 TEMPERATURE PROBE CONNECTED TO A 686 00:23:10,080 --> 00:23:10,960 MONITOR THAT TELLS ME THAT IN 687 00:23:10,960 --> 00:23:14,400 EVERY PART OF THE ABDOMINAL 688 00:23:14,400 --> 00:23:15,360 CAVITY THE HYPOTHERMOGENESISSIC 689 00:23:15,360 --> 00:23:17,080 CHEMO THERAPY IS REACHING THAT 690 00:23:17,080 --> 00:23:17,280 AREA. 691 00:23:17,280 --> 00:23:21,440 AND OF COURSE IT HEATS IT AND 692 00:23:21,440 --> 00:23:22,960 RECIRCULATES IT. 693 00:23:22,960 --> 00:23:24,960 THIS HAPPENS FOR AN HOUR AND A 694 00:23:24,960 --> 00:23:25,880 HALF IN THE OPERATE HAPPENING 695 00:23:25,880 --> 00:23:28,480 ROOM WHILE THE PATIENT'S 696 00:23:28,480 --> 00:23:32,280 SLEEPING IN THE OPERATING ROOM 697 00:23:32,280 --> 00:23:33,920 AT 41-DEGREES CELSIUS, THIS IS 698 00:23:33,920 --> 00:23:36,560 HOW IT LOOKS, THIS IS THE IN 699 00:23:36,560 --> 00:23:38,880 FLOW, OUT FLOW AND PROBES, AND 700 00:23:38,880 --> 00:23:39,680 FINE CONSTITUTURING THE 69 TO 701 00:23:39,680 --> 00:23:40,920 KEEP IT WATER TIGHT DURING THE 702 00:23:40,920 --> 00:23:44,000 PROCEDURE AND I CHOSE TO USE 703 00:23:44,000 --> 00:23:46,040 THIS SIS PLATIN FOR THE FIRST 704 00:23:46,040 --> 00:23:49,480 TIME IN CHILDREN BECAUSE IT HAD 705 00:23:49,480 --> 00:23:51,320 NO LOCAL PERITONEUM TOXICITY, NO 706 00:23:51,320 --> 00:23:52,880 TOXICITY FOR DRUGS GIVEN 707 00:23:52,880 --> 00:23:55,520 PREVIOUSLY AND YOU GIVE ANN 708 00:23:55,520 --> 00:23:57,160 NEUTRALIZING AGENT TO BIND UP 709 00:23:57,160 --> 00:23:58,080 THE SIS PLATIN AND AG GREEN 710 00:23:58,080 --> 00:23:59,400 CELLS IMAIT SIDE EFFECTS FROM 711 00:23:59,400 --> 00:24:00,760 THE CHEMO THERAPY DRUG. 712 00:24:00,760 --> 00:24:02,680 THE DIRECT CONTACT OF THE SIS 713 00:24:02,680 --> 00:24:03,840 PLATIN TO THE TISSUES IS WHAT'S 714 00:24:03,840 --> 00:24:05,360 VERY IMPORTANT AND THAT'S 715 00:24:05,360 --> 00:24:07,560 BECAUSE VERY LITTLE OF IT GETS 716 00:24:07,560 --> 00:24:08,520 ABSORBED INTO THE BLOOD STREAM. 717 00:24:08,520 --> 00:24:11,720 SO HOW THIS WORKS IS THAT YOU 718 00:24:11,720 --> 00:24:13,240 HAVE THIS RESPONSE TO 719 00:24:13,240 --> 00:24:15,160 HYPOTHERMIA AND NORMAL TISSUES 720 00:24:15,160 --> 00:24:17,960 ARE REALLY FINE UNTIL YOU GET UP 721 00:24:17,960 --> 00:24:18,880 TO ABOUT 50-DEGREES CELSIUS, 722 00:24:18,880 --> 00:24:22,080 REMEMBER I SAID WE'RE DOING THIS 723 00:24:22,080 --> 00:24:23,960 AT 41.5-DEGREES CELSIUS, THE 724 00:24:23,960 --> 00:24:25,480 BLOOD FLOW THROUGH CANCER 725 00:24:25,480 --> 00:24:27,320 TISSUES INCREASES TO A LESSER 726 00:24:27,320 --> 00:24:28,960 EXTENT AND STASIS OCCURS WHICH 727 00:24:28,960 --> 00:24:30,960 CAN ADD TO CELLULAR TOXICITY AND 728 00:24:30,960 --> 00:24:32,840 THE HEAT PLUS CHEMO THERAPY 729 00:24:32,840 --> 00:24:34,040 SYNERGIZED TO KILL THE 730 00:24:34,040 --> 00:24:35,880 MICROSCOPIC CELLS THAT ARE LEFT 731 00:24:35,880 --> 00:24:37,400 BEHIND AFTER SURGICAL REMOVAL. 732 00:24:37,400 --> 00:24:38,800 THERE ARE ONLY CERTAIN CHEMO 733 00:24:38,800 --> 00:24:41,200 THERAPY DRUGS THAT ARE SINNER 734 00:24:41,200 --> 00:24:43,000 GESTIC WITH HYPOTHERMIA, I CHOSE 735 00:24:43,000 --> 00:24:44,800 SIS PLATIN BECAUSE IT HAD THE 736 00:24:44,800 --> 00:24:45,960 LOWEST TOXICITY PROFILE AND A 737 00:24:45,960 --> 00:24:51,200 HINT OF EFFICACY AND SARCOMAS. 738 00:24:51,200 --> 00:24:53,080 ALSO, THE SIS PLATIN STAYS IN 739 00:24:53,080 --> 00:24:54,800 THE ABDOMINAL CAVITY, SO THAT 740 00:24:54,800 --> 00:24:56,720 VERY LITTLE OF IT GETS ABSORBED 741 00:24:56,720 --> 00:24:58,960 IN THE BLOOD STREAM. 742 00:24:58,960 --> 00:25:01,640 MAYBE ONLY 2-5% GETS ABSORBED IN 743 00:25:01,640 --> 00:25:02,760 THE BLOOD STREAM. 744 00:25:02,760 --> 00:25:04,360 SO WHAT TYPE OF PATIENTS MIGHT 745 00:25:04,360 --> 00:25:06,320 NEED THIS PROCEDURE, THIS IS A 746 00:25:06,320 --> 00:25:08,120 PATIENT OF MINE THAT I MET WHEN 747 00:25:08,120 --> 00:25:09,440 I FIRST STARTED THE CLINICAL 748 00:25:09,440 --> 00:25:12,960 TRIAL, SHE WAS ALMOST 3 YEARS 749 00:25:12,960 --> 00:25:16,400 OLD AND THE ONCOLOGIST CALLED ME 750 00:25:16,400 --> 00:25:18,240 A BIT SHEEPISHLY AND SAID I AM 751 00:25:18,240 --> 00:25:20,440 SO SORRY TO BOTHER YOU, I TRIED 752 00:25:20,440 --> 00:25:22,080 TO TREAT THIS PATIENT WITH CHEMO 753 00:25:22,080 --> 00:25:23,040 THERAPY AND NOTHING'S WORKING 754 00:25:23,040 --> 00:25:26,920 AND I'M ABOUT TO SEND THEM HOME 755 00:25:26,920 --> 00:25:28,680 ON HOSPICE, THE MOTHER'S 756 00:25:28,680 --> 00:25:30,280 INSISTING ON SPEAKING WITH A 757 00:25:30,280 --> 00:25:31,640 SURGEON BEFORE LEAVING THE 758 00:25:31,640 --> 00:25:31,920 HOSPITAL. 759 00:25:31,920 --> 00:25:33,160 WOULD YOU MIND SPEAKING WITH 760 00:25:33,160 --> 00:25:33,600 THEM. 761 00:25:33,600 --> 00:25:35,640 THIS IS THE PET SCAN AND THE 762 00:25:35,640 --> 00:25:38,040 IMAGING, YOU CAN SEE THE OUTLINE 763 00:25:38,040 --> 00:25:39,920 OF THE SKELETON OF THE LITTLE 764 00:25:39,920 --> 00:25:42,120 AND HERE'S THE SPOTS WITH THE 765 00:25:42,120 --> 00:25:44,440 TUMORS IN THE ABDOMEN AND, THE 766 00:25:44,440 --> 00:25:46,320 BLADDER'S THE ONLY THING NORMAL 767 00:25:46,320 --> 00:25:47,840 IN THIS IMAGE, THE REST OF IT 768 00:25:47,840 --> 00:25:50,840 THAT ARE LIT UP THERE ARE FROM 769 00:25:50,840 --> 00:25:53,600 THE TUMORS AND YOU CAN SEE ON 770 00:25:53,600 --> 00:25:56,120 THE CAT SCAN SHE HAS TONS OF 771 00:25:56,120 --> 00:25:56,680 TUMORS IN HER LIVER. 772 00:25:56,680 --> 00:25:57,880 I SAID WE'RE DOING THIS NEW 773 00:25:57,880 --> 00:25:59,080 TRIAL, I DON'T KNOW IF WE WILL 774 00:25:59,080 --> 00:26:00,920 WORK BUT WE WILL TRY IT IN YOUR 775 00:26:00,920 --> 00:26:04,120 DAUGHTER AND WE DID AND WE WERE 776 00:26:04,120 --> 00:26:06,200 ABLE TO REMOVE A HUNDRED PERCENT 777 00:26:06,200 --> 00:26:09,680 OF HER TUMORS AND DO THE HYPACK, 778 00:26:09,680 --> 00:26:11,920 AND I LOST TRACK OF HER WHEN SHE 779 00:26:11,920 --> 00:26:13,360 GOT TO EIGHTH OR NINTH GRADE 780 00:26:13,360 --> 00:26:14,640 BECAUSE SHE DID WELL FOR 10 781 00:26:14,640 --> 00:26:15,720 YEARS PLUS AFTER THAT AND YOU 782 00:26:15,720 --> 00:26:18,200 CAN SEE IN THIS IMAGE THERE'S NO 783 00:26:18,200 --> 00:26:19,600 TUMOR JUST NORMAL KIDNEYS AND 784 00:26:19,600 --> 00:26:19,840 BLADDER. 785 00:26:19,840 --> 00:26:21,640 THIS IS ANOTHER EXAMPLE OF A 13 786 00:26:21,640 --> 00:26:22,800 YEAR-OLD BOY WHO CAME TO ME 787 00:26:22,800 --> 00:26:25,680 AFTER HE HAD BEEN OPERATED AT A 788 00:26:25,680 --> 00:26:27,320 DIFFERENT HOSPITAL, AND HIS 789 00:26:27,320 --> 00:26:30,440 TUMOR HAD ACTUALLY GREW AFTER 790 00:26:30,440 --> 00:26:32,600 HIS OPERATION THAT THE SURGEON 791 00:26:32,600 --> 00:26:34,680 TOOK OUT PAROF IT BUT NOT ALL OF 792 00:26:34,680 --> 00:26:38,360 IT, THIS IS A INCISION FROM THE 793 00:26:38,360 --> 00:26:41,160 SURGERY, WE HAD GIVEN HIM 794 00:26:41,160 --> 00:26:42,920 MAXIMAL CHEMO THERAPY, WE ARE IN 795 00:26:42,920 --> 00:26:48,080 A DILLAMY BECAUSE THIS WAS THE 796 00:26:48,080 --> 00:26:50,840 ONLY TUMOR IN HIS BODY, AND HE 797 00:26:50,840 --> 00:26:52,720 NEEDED TO DO IT QUICKLY BECAUSE 798 00:26:52,720 --> 00:26:53,760 HE COULD BT REALLY BREATHE DUE 799 00:26:53,760 --> 00:26:54,760 TO THE SIZE OF THE TUMOR. 800 00:26:54,760 --> 00:26:56,480 SO THIS IS THE AT END OF THE 801 00:26:56,480 --> 00:26:57,880 SURGERY WHERE I WAS ABLE TO 802 00:26:57,880 --> 00:26:59,960 REMOVE THE WHOLE TUMOR IN 1 803 00:26:59,960 --> 00:27:03,040 PIECE, THIS IS THE PATIENT 804 00:27:03,040 --> 00:27:05,000 AFTERWARDS WAKING UP IN SURGERY. 805 00:27:05,000 --> 00:27:07,440 AND IN THE OPERATING ROOM, 806 00:27:07,440 --> 00:27:09,200 AGAIN, THE FEET ARE TO YOUR 807 00:27:09,200 --> 00:27:10,160 LEFT, HEADS TO YOUR RIGHT, 808 00:27:10,160 --> 00:27:12,840 YOU'RE LOOKING DOWN INTO WHERE 809 00:27:12,840 --> 00:27:15,120 THE TUMOR WAS, MY HAND'S ON THE 810 00:27:15,120 --> 00:27:17,920 SMALL BOWEL, THE COLON IS 811 00:27:17,920 --> 00:27:19,160 TRANSECTOMYOSINNED SO A SMALL 812 00:27:19,160 --> 00:27:20,600 PIECE OF COLON WAS REMOVED WITH 813 00:27:20,600 --> 00:27:22,160 THE TUMOR YOU CAN SEE THE LEFT 814 00:27:22,160 --> 00:27:22,440 AND RIGHT. 815 00:27:22,440 --> 00:27:25,040 YOU CAN SEE THE BLOOD VESSELS 816 00:27:25,040 --> 00:27:26,200 AND THERE WASN'T REALLY ANY 817 00:27:26,200 --> 00:27:27,520 INVASION OF THE ORGANS AND THE 818 00:27:27,520 --> 00:27:29,200 LARGE MASS WAS ABLE TO BE 819 00:27:29,200 --> 00:27:29,440 REMOVED. 820 00:27:29,440 --> 00:27:32,400 THIS IS ANOTHER EXAMPLE OF A 12 821 00:27:32,400 --> 00:27:34,320 YEAR-OLD GIRL WITH A SIMILAR 822 00:27:34,320 --> 00:27:35,840 TUMOR THAT WAS OVARIAN AND HAD A 823 00:27:35,840 --> 00:27:38,280 RELAPSE AND I WENT TO KENYA TO 824 00:27:38,280 --> 00:27:39,680 DO HER OPERATION--EXCUSE ME--AND 825 00:27:39,680 --> 00:27:44,920 WAS ABLE TO REMOVE THE TUMOR AND 826 00:27:44,920 --> 00:27:51,960 SEND HER BACK TO HER VILLAGE. 827 00:27:51,960 --> 00:27:53,480 SO THE JOURNEY BEGAN IN TRYING 828 00:27:53,480 --> 00:27:55,000 TO ESTABLISH THIS NEW APPROACH. 829 00:27:55,000 --> 00:27:59,000 WE OPENED A PHASE 1 TRIAL. 830 00:27:59,000 --> 00:28:01,000 AND WE TAKE THE FIRST 10 831 00:28:01,000 --> 00:28:02,520 PATIENTS AND TRY TO 832 00:28:02,520 --> 00:28:03,560 ESKACCTCULATE THE DOSE OF THE 833 00:28:03,560 --> 00:28:06,360 SIS PLATIN TO SEE IF WE CAN GET 834 00:28:06,360 --> 00:28:08,440 TO AN EFFICACIOUS AND SAFE DOSE, 835 00:28:08,440 --> 00:28:09,800 NOW I'VE DONE OVER 200 PATIENTS 836 00:28:09,800 --> 00:28:12,360 TO DATE BUT THIS IS THE RESULT 837 00:28:12,360 --> 00:28:14,160 OF THE FIRST 27 HIPEC PROCEDURES 838 00:28:14,160 --> 00:28:18,320 AND AT THE TIME WE TOOK ALL 839 00:28:18,320 --> 00:28:20,000 COMERS, ALL DIAGNOSIS, AND IT 840 00:28:20,000 --> 00:28:30,520 TOOK ME A WHILE TO FIGURE OUT 841 00:28:32,680 --> 00:28:35,000 THAT THE DSRCT WAS PRETTY LOW. 842 00:28:35,000 --> 00:28:37,480 WE START OFF WITH 45.41-DEGREES 843 00:28:37,480 --> 00:28:40,840 CELSIUS AND WE TRY TO GO UP TO 844 00:28:40,840 --> 00:28:41,640 150-MILLIGRAMS PER METERS 845 00:28:41,640 --> 00:28:45,920 SQUARED AND WE ENCOUNTERED 846 00:28:45,920 --> 00:28:47,040 TOXICITY THAT WE WILL FILE 847 00:28:47,040 --> 00:28:48,800 SHORTLY AND WE FOLLOWED THE 848 00:28:48,800 --> 00:28:49,960 PATIENTS FOR 5 YEARS, OPERATIVE 849 00:28:49,960 --> 00:28:51,760 TIME AT THAT POINT WAS ABOUT 15 850 00:28:51,760 --> 00:28:54,000 HOURS AT MAXIMUM. 851 00:28:54,000 --> 00:28:56,080 AND THE AVERAGE HOSPITAL STAY IS 852 00:28:56,080 --> 00:28:56,560 10-12 DAYS. 853 00:28:56,560 --> 00:28:57,960 WE DID A PARALLEL QUALITY OF 854 00:28:57,960 --> 00:28:59,160 LIFE STUDY THAT I DON'T HAVE 855 00:28:59,160 --> 00:29:00,920 TIME TO SHARE ALL THE DETAILS 856 00:29:00,920 --> 00:29:03,440 BUT SUFFICE IT TO SAY THAT WHAT 857 00:29:03,440 --> 00:29:05,640 WE FOUND WAS FROM ANYWHERE FROM 858 00:29:05,640 --> 00:29:06,960 30-60 DAYS THE PATIENT WAS BACK 859 00:29:06,960 --> 00:29:11,200 TO THEIR NORMAL ACTIVITY AND 860 00:29:11,200 --> 00:29:11,880 DOING EVERYTHING NORMALLY. 861 00:29:11,880 --> 00:29:13,600 IN THE PHASE 1 STUDY, WE FOUND 862 00:29:13,600 --> 00:29:15,960 THAT GRADE 3 RENAL FAILURE WAS 863 00:29:15,960 --> 00:29:17,080 THE DOSE LIMITING TOXICITY AND 864 00:29:17,080 --> 00:29:19,360 6% OF THE PATIENTS REQUIRED 865 00:29:19,360 --> 00:29:20,520 DIALYSIS, THAT'S WHETHER I SHUT 866 00:29:20,520 --> 00:29:21,840 THE PROTOCOL DOWN AND BEGAN TO 867 00:29:21,840 --> 00:29:25,720 DO A VERY DETAILED EVALUATION: 868 00:29:25,720 --> 00:29:29,400 THE OTHER TOXICITIES WERE VERY 869 00:29:29,400 --> 00:29:32,560 MINIMAL, SUBCLINICAL DECREASE IN 870 00:29:32,560 --> 00:29:33,840 HEARING, HEMOTO LOGIC TOXICITIES 871 00:29:33,840 --> 00:29:34,840 THAT REVERSED OVER A FEW DAYS 872 00:29:34,840 --> 00:29:35,960 TIME AND A PATIENT THAT HAD TO 873 00:29:35,960 --> 00:29:42,560 COME BACK TO THE HOSPITAL FOR 874 00:29:42,560 --> 00:29:45,640 ILEUS, TO AFTER THIS TRIAL AND 875 00:29:45,640 --> 00:29:52,600 TO DATE I HAVE HAD NO MORE DEATH 876 00:29:52,600 --> 00:29:55,000 IN CHILDREN. 877 00:29:55,000 --> 00:29:56,280 ONE PATIENT HAD CARDIO MYOPATHY, 878 00:29:56,280 --> 00:29:58,520 I TOOK OUT OVER A KILOOF TUMOR 879 00:29:58,520 --> 00:30:00,800 IN THIS PATIENT AND THE 880 00:30:00,800 --> 00:30:01,720 CARDIOLOGIST EXPLAINED TO ME 881 00:30:01,720 --> 00:30:02,720 THAT THIS STUNS THE HEART, 882 00:30:02,720 --> 00:30:05,040 ALTHOUGH HE HAD NO SYMPTOMS HE 883 00:30:05,040 --> 00:30:05,920 REQUIRED BETA BLOCKERS IN ORDER 884 00:30:05,920 --> 00:30:08,160 FOR HIM TO BE ABLE TO DO 885 00:30:08,160 --> 00:30:13,120 ACTIVITY AND THEN PARTIAL SMALL 886 00:30:13,120 --> 00:30:14,960 BOWEL OBSTRUCTION CAN OCCUR. 887 00:30:14,960 --> 00:30:17,720 IN THIS COHORT OR TO TO DATE I 888 00:30:17,720 --> 00:30:18,840 HAVE NOT HAD TO TAKE ANY 889 00:30:18,840 --> 00:30:23,600 PATIENTS BACK TO THE OPERATING ROOM 890 00:30:23,600 --> 00:30:28,480 WE'RE DRAWING SO AT A CANCER 891 00:30:28,480 --> 00:30:29,880 CENTER, WE'RE ARGUELY HAVING 892 00:30:29,880 --> 00:30:32,440 EXCELLENT CARE IF NOT THE BEST 893 00:30:32,440 --> 00:30:34,320 CARE, FROM 1999-2003 YOU CAN SEE 894 00:30:34,320 --> 00:30:36,200 IN THIS SURVIVAL CAP LANMIER 895 00:30:36,200 --> 00:30:37,840 CURVE THAT ONLY 10% OF THE 896 00:30:37,840 --> 00:30:39,040 PATIENTS WERE SURVIVINGA THE A 897 00:30:39,040 --> 00:30:40,200 HUNDRED MONTHS. 898 00:30:40,200 --> 00:30:44,360 I ARRIVED AT M. D. ANDERSON FROM 899 00:30:44,360 --> 00:30:45,440 2004, FROM 2004-2010, IN THAT 6 900 00:30:45,440 --> 00:30:47,200 YEAR TIME PERIOD I WAS ABLE TO 901 00:30:47,200 --> 00:30:49,640 GET A 50% SURVIVAL IN THIS 902 00:30:49,640 --> 00:30:54,240 COHORT OF DSRCT PATIENTS WITH MY 903 00:30:54,240 --> 00:30:54,520 APPROACH. 904 00:30:54,520 --> 00:30:55,200 SO ABOUT THE TOXICITY. 905 00:30:55,200 --> 00:30:56,600 IT'S VERY CONCERNING TO ME, I 906 00:30:56,600 --> 00:30:57,800 NEVER WANT TO HURT A PATIENT 907 00:30:57,800 --> 00:30:59,280 DOING THIS BUT ONLY HELP THEM OF 908 00:30:59,280 --> 00:30:59,520 COURSE. 909 00:30:59,520 --> 00:31:01,920 SO I DID A VERY DETAILED 910 00:31:01,920 --> 00:31:03,400 ANALYSIS WITH 21 DIFFERENT 911 00:31:03,400 --> 00:31:04,880 VARIABLES, TO TRY TO UNDERSTAND 912 00:31:04,880 --> 00:31:06,240 ANYTHING AND EVERYTHING THAT 913 00:31:06,240 --> 00:31:08,480 COULD AFFECT THE KIDNEY 914 00:31:08,480 --> 00:31:10,720 SO THIS RENAL TOXISITY IS 915 00:31:10,720 --> 00:31:12,040 WHAT WE MEASURED IN 10 PATIENTS 916 00:31:12,040 --> 00:31:13,640 AND THE 3 THAT REQUIRED DIALYSIS 917 00:31:13,640 --> 00:31:15,080 WHICH IS WHY WE SHUT THE 918 00:31:15,080 --> 00:31:16,360 PROTOCOL DOWN AND AFTER LOOKING 919 00:31:16,360 --> 00:31:18,480 AT ALL OF THE VARIABLES, WHAT I 920 00:31:18,480 --> 00:31:21,560 FOUND WAS THAT THE PREOPERATIVE 921 00:31:21,560 --> 00:31:23,000 HYDRATION AND SODIUM SULFATE 922 00:31:23,000 --> 00:31:28,680 CONTRIBUTED TO THE MOST TO THE 923 00:31:28,680 --> 00:31:29,480 OUTCOME OR STATISTICALLY 924 00:31:29,480 --> 00:31:33,200 SIGNIFICANT IN HOW THEY IMPACTED 925 00:31:33,200 --> 00:31:34,440 THE RENAL FAILURE. 926 00:31:34,440 --> 00:31:36,080 SO WHEN I THEY FIRST STARTED WE 927 00:31:36,080 --> 00:31:37,480 WERE UNABLE TO ADMIT THE 928 00:31:37,480 --> 00:31:38,480 PATIENTS TO THE HOSPITAL THE DAY 929 00:31:38,480 --> 00:31:41,080 BEFORE AND WE HAD TO--THE 930 00:31:41,080 --> 00:31:43,400 INSURANCE COMPANY ALLOW US TO 931 00:31:43,400 --> 00:31:44,720 ADTHEM ON THE DAY BEFORE AND WE 932 00:31:44,720 --> 00:31:46,800 CAN'T DO THAT, IT WAS VERY HARD 933 00:31:46,800 --> 00:31:48,800 FOR RENAL FAILURE AND THE OTHER 934 00:31:48,800 --> 00:31:50,320 VALUE THAT WAS STATISTICALLY 935 00:31:50,320 --> 00:31:51,320 SIGNIFICANT WAS THE TIMING OF 936 00:31:51,320 --> 00:31:55,160 THE DELIVERY OF THE SODIUM 937 00:31:55,160 --> 00:31:57,800 THIOSULFATE WHICH BINDS UP THE 938 00:31:57,800 --> 00:31:59,280 SIS PLATIN MOLECULES SO IF YOU 939 00:31:59,280 --> 00:32:02,240 WAIT UNTIL THE END OF THE 90 940 00:32:02,240 --> 00:32:04,680 MINUTE INFUSION OF SIS PLATIN 941 00:32:04,680 --> 00:32:07,240 YOU WILL GET A HIGHER TOXICITY 942 00:32:07,240 --> 00:32:09,240 AT THE BEGINNING OF THE DRUG OR 943 00:32:09,240 --> 00:32:10,000 PROCEDURE AND THAT'S LAWEDDER 944 00:32:10,000 --> 00:32:11,560 DALE WE STARTED DOING AND ONCE 945 00:32:11,560 --> 00:32:13,520 WE MADE THE CHANGES WE HAVE NOT 946 00:32:13,520 --> 00:32:17,520 HAD ANY INCIDENCE OF RENAL 947 00:32:17,520 --> 00:32:18,920 INSUFFICIENCY OR RENAL FAILURE 948 00:32:18,920 --> 00:32:19,720 FROM THESE PROCEDURES. 949 00:32:19,720 --> 00:32:21,920 MY FIRST RESULTS I PUBLISHED IN 950 00:32:21,920 --> 00:32:24,560 2013 SPECIFICALLY ON THE DSRCT 951 00:32:24,560 --> 00:32:27,280 REMEMBER WE TOOK ALL HISTOLOGIES 952 00:32:27,280 --> 00:32:28,200 FOR A WHILE, NARROWING IT DOWN 953 00:32:28,200 --> 00:32:29,760 TO THE 1S THAT ARE EFFECTIVE AND 954 00:32:29,760 --> 00:32:31,400 WHEN WE LOOKED WE SELECTED 955 00:32:31,400 --> 00:32:33,360 PATIENTS THAT HAD NO DISEASE 956 00:32:33,360 --> 00:32:35,440 OUTSIDE THE ABDOMINAL CAVITY. 957 00:32:35,440 --> 00:32:38,280 THE PATIENTS WERE CYTOREDUCE TD 958 00:32:38,280 --> 00:32:40,640 TO A SMALL TUMOR THAT MIGHT BE 959 00:32:40,640 --> 00:32:42,680 AMENABLE TO RADIATION, REMEMBER 960 00:32:42,680 --> 00:32:46,080 THIS IS A EWING TYPE SARCOMA 961 00:32:46,080 --> 00:32:47,160 BIOLOGICALLY, SO EWING SARCOMA 962 00:32:47,160 --> 00:32:48,920 RESPONDS WELL TO RADIATION. 963 00:32:48,920 --> 00:32:52,560 SO WE PROVIDED RADIATION EITHER 964 00:32:52,560 --> 00:32:54,520 IN 1 SPOT AND/OR THE WHOLE 965 00:32:54,520 --> 00:32:56,760 ABDOMEN AND WITH THAT NEW 966 00:32:56,760 --> 00:32:58,720 PARADIGM THE SURVIVAL IMPROVED 967 00:32:58,720 --> 00:33:03,400 FROM 26 MONTHS TO 63 MONTHS. 968 00:33:03,400 --> 00:33:04,800 MOVING FORWARD NOW TO THE PHASE 969 00:33:04,800 --> 00:33:06,400 2 STUDY THAT WAS START INDEED 970 00:33:06,400 --> 00:33:09,720 2016, WE NOW HAD LEARNED EXACTLY 971 00:33:09,720 --> 00:33:12,400 WHICH PATIENTS TO SELECT AND WE 972 00:33:12,400 --> 00:33:14,240 DID A PHASE 2 EFFICACY TRIAL 973 00:33:14,240 --> 00:33:16,600 LOOKING AT PATIENTS FROM AGE 22 974 00:33:16,600 --> 00:33:19,800 MONTHS TO 50 YEARS AND WE USED 975 00:33:19,800 --> 00:33:21,640 SIS PLATIN AT A HUNDRED 976 00:33:21,640 --> 00:33:23,840 MILLIGRAMS PER METER SQUARED. 977 00:33:23,840 --> 00:33:25,800 WE DID LEARN THAT WE HAD TO 978 00:33:25,800 --> 00:33:27,560 EXCLUDE PATIENTS WHO DID NOT 979 00:33:27,560 --> 00:33:29,160 RESPOND TO CHEMO THERAPY THAT 980 00:33:29,160 --> 00:33:31,280 WAS GIVEN IN A NEW ADJUVANT 981 00:33:31,280 --> 00:33:32,640 STETTING, WE COULD NOT ACCEPT 982 00:33:32,640 --> 00:33:34,720 PATIENTS THAT HAD ANY DISEASE 983 00:33:34,720 --> 00:33:35,920 OUTSIDE THE ABDOMINAL CAVITY, 984 00:33:35,920 --> 00:33:38,000 AND ANY PATIENTS THAT HAD POOR 985 00:33:38,000 --> 00:33:40,000 PERFORMANCE STATUS OR ANY 986 00:33:40,000 --> 00:33:40,680 PATIENTS WITH ORGAN DYSFUNCTION. 987 00:33:40,680 --> 00:33:43,200 WE COULD NONAPOPTOTIC THE 988 00:33:43,200 --> 00:33:44,560 RECEIVE--WE COULD NOT DO THIS 989 00:33:44,560 --> 00:33:47,040 PROCEDURE IF WHEN I LOOKEDDA THE 990 00:33:47,040 --> 00:33:49,360 IMAGING, I THOUGHT A HUNDRED% OF 991 00:33:49,360 --> 00:33:50,600 THE DISEASE COULD NTD BE REMOVED 992 00:33:50,600 --> 00:33:52,240 YOU HAVE TO REMOVE A HUNDRED 993 00:33:52,240 --> 00:33:54,280 PERCENT OF WHAT YOU CAN SEE IN 994 00:33:54,280 --> 00:33:57,080 ORDER TO SEE ANY CHANGE. 995 00:33:57,080 --> 00:33:58,880 SO FROM 2012-2013 WE MET OUR 996 00:33:58,880 --> 00:33:59,120 ACCRUAL. 997 00:33:59,120 --> 00:34:01,200 FOURTEEN OF THE PATIENTS HAD 998 00:34:01,200 --> 00:34:04,120 DSRCT AND 6 HAD OTHER DIAGNOSIS. 999 00:34:04,120 --> 00:34:08,560 ALL PATIENTS HAD NEW ADJUVANT 1000 00:34:08,560 --> 00:34:10,440 CHEMO THERAPY FOLLOWED BY NEW 1001 00:34:10,440 --> 00:34:12,920 CYCLES FOLLOWED BY REDUCTIVE 1002 00:34:12,920 --> 00:34:15,760 SURGERY AND THE HIPEC, AND THEN 1003 00:34:15,760 --> 00:34:17,080 THEY HAD RADIATION THERAPY AND 1004 00:34:17,080 --> 00:34:18,720 AMILLIOY AND CHEMO THERAPY 1005 00:34:18,720 --> 00:34:19,800 BEFORE SURVEILLANCE. 1006 00:34:19,800 --> 00:34:21,960 THE ESTIMATED 1 YEAR SURVIVAL IS 1007 00:34:21,960 --> 00:34:25,320 93% FOR THE DSRCT PATIENTS AND 1008 00:34:25,320 --> 00:34:26,720 TD MEDIAN SURVIVAL WAS NOT 1009 00:34:26,720 --> 00:34:29,880 REACHED FOR THE DSRCT PATIENTS. 1010 00:34:29,880 --> 00:34:31,400 THE RAB DO MYOSARCOMA AND OTHER 1011 00:34:31,400 --> 00:34:32,480 PATIENTS IN THE STUDY DOES NOT 1012 00:34:32,480 --> 00:34:34,360 DO WELL AND DID NOT RESPOND TO 1013 00:34:34,360 --> 00:34:36,200 THE TREATMENT. 1014 00:34:36,200 --> 00:34:40,400 THIS IS ANOTHER KAPLAN MIER 1015 00:34:40,400 --> 00:34:43,080 CURVE WITH PATIENTS OF ALL 1016 00:34:43,080 --> 00:34:44,600 PATIENTS AT 63% AT 3 YEARS. 1017 00:34:44,600 --> 00:34:47,080 BUT WHEN YOU SEPARATE THE DSRCT 1018 00:34:47,080 --> 00:34:50,080 PATIENTS FROM THE OTHER 1019 00:34:50,080 --> 00:34:51,840 PATIENTS, YOU SEE A STRIKING 1020 00:34:51,840 --> 00:34:52,480 DIFFERENCE IN SURVIVAL. 1021 00:34:52,480 --> 00:34:55,080 THE BLACK LINE IS THE DSRCT 1022 00:34:55,080 --> 00:34:57,040 PATIENTS AND THIS IS SURVIVAL 1023 00:34:57,040 --> 00:34:58,880 CAP LANMIER CURVE SO CAN YOU SEE 1024 00:34:58,880 --> 00:35:01,800 THAT AT 30 MONTHS THAT THERE'S 1025 00:35:01,800 --> 00:35:03,400 80% SURVIVAL IN THE DSRCT 1026 00:35:03,400 --> 00:35:04,360 PATIENTS COMPARED TO THE OTHER 1027 00:35:04,360 --> 00:35:11,880 PATIENTS FOR WHICH ALL OF THEM 1028 00:35:11,880 --> 00:35:13,120 FOR 15 MONTHS. 1029 00:35:13,120 --> 00:35:14,840 AGAIN THIS IS THE DISEASE 1030 00:35:14,840 --> 00:35:19,280 SURVIVAL, THE BLACK LINE IS THE 1031 00:35:19,280 --> 00:35:20,280 DSRCT PATIENTS AND THE OTHER 1032 00:35:20,280 --> 00:35:23,400 LINES ARE PATIENTS WITH OTHER 1033 00:35:23,400 --> 00:35:23,640 DIAGNOSIS. 1034 00:35:23,640 --> 00:35:25,000 SOPHISTICATED WHEN I LOOK AT THE 1035 00:35:25,000 --> 00:35:26,240 DATA MORE CAREFULLY AND FOLLOW 1036 00:35:26,240 --> 00:35:28,240 THE PATIENTS LONGER, WHAT I 1037 00:35:28,240 --> 00:35:31,200 FOUND WAS THAT HERE'S THE 80% 1038 00:35:31,200 --> 00:35:32,280 SURVIVAL AT 30 MONTHS ABOUT YOU 1039 00:35:32,280 --> 00:35:35,840 WHEN YOU WAIT LONGER THAN 1040 00:35:35,840 --> 00:35:36,720 30-MONTHS, THE DISEASE STARTS TO 1041 00:35:36,720 --> 00:35:38,080 OCCUR AND OTHER PARTS OF THE 1042 00:35:38,080 --> 00:35:40,520 BODY, SO THEY DON'T HAVE--I HAVE 1043 00:35:40,520 --> 00:35:42,640 1 PATIENT THAT A RECURRENCE IN L 1044 00:35:42,640 --> 00:35:43,600 ABDOMEN IN THEIR PATIENTS BUT 1045 00:35:43,600 --> 00:35:44,560 MOST OF THE TIME THEY DON'T 1046 00:35:44,560 --> 00:35:47,240 OCCUR AT ALL IN THE ABDOMEN, IT 1047 00:35:47,240 --> 00:35:48,880 STAYS PRISTINE BUT UNFORTUNATELY 1048 00:35:48,880 --> 00:35:51,320 THE TUMOR COMES BA IN THEIR 1049 00:35:51,320 --> 00:35:55,400 LYMPHNODES OR AREAS OF THE LUNGS 1050 00:35:55,400 --> 00:35:57,120 AND CHEST AND BONES AND BRAIN. 1051 00:35:57,120 --> 00:36:00,200 SO THIS REALLY MOTIVATED ME TO 1052 00:36:00,200 --> 00:36:01,240 UNDERSTAND THE DISEASE SO NOW WE 1053 00:36:01,240 --> 00:36:03,080 UNDERSTAND HOW TO TAKE CARE OF 1054 00:36:03,080 --> 00:36:04,360 THE LOCAL DISEASE BUT WE REALLY 1055 00:36:04,360 --> 00:36:06,680 WANT THE HOME RUN TO BE ABLE TO 1056 00:36:06,680 --> 00:36:09,120 CURE THE DISEASE ALTOGETHER. 1057 00:36:09,120 --> 00:36:12,040 SO I WILL TELL YOU BRIEFLY HOW 1058 00:36:12,040 --> 00:36:13,440 I'M TRYING TO CHANGE THE STAGING 1059 00:36:13,440 --> 00:36:15,280 OF THIS DISEASE AND THEN WE WILL 1060 00:36:15,280 --> 00:36:18,040 TALK ABOUT THE SCIENCE BEHIND 1061 00:36:18,040 --> 00:36:18,200 IT. 1062 00:36:18,200 --> 00:36:19,760 SO IF EVERY PATIENT PRESENTS 1063 00:36:19,760 --> 00:36:22,960 WITH MORE THAN A TUMOR, IN 1064 00:36:22,960 --> 00:36:25,680 SARCOMAS, WE CALL THAT A STAGE 4 1065 00:36:25,680 --> 00:36:25,920 PATIENT. 1066 00:36:25,920 --> 00:36:28,040 EVERY PATIENT CAN BE A STAGE 4 1067 00:36:28,040 --> 00:36:29,120 BECAUSE THEY'RE ALL DIFFERENT. 1068 00:36:29,120 --> 00:36:31,520 SO I KREALT A NEW STAGING SYSTEM 1069 00:36:31,520 --> 00:36:32,880 THAT HASN'T YET BEEN VALIDATED 1070 00:36:32,880 --> 00:36:35,440 THAT STAGE 1 TUMORS ARE JUST IN 1071 00:36:35,440 --> 00:36:36,040 THE [INDISCERNIBLE]. 1072 00:36:36,040 --> 00:36:37,160 THEY HAVE SEVERAL OF THOSE THAT 1073 00:36:37,160 --> 00:36:39,680 ARE DOING VERY WELL. 1074 00:36:39,680 --> 00:36:41,280 STAGE 2 TUMORS DOESN'T HAVE MANY 1075 00:36:41,280 --> 00:36:44,320 TUMORS BUT THEY DON'T HAVE ANY 1076 00:36:44,320 --> 00:36:45,920 LIVER METASTASIS AND THEY DON'T 1077 00:36:45,920 --> 00:36:49,160 HAVE ANY LYMPHNODE OR ANY OTHER 1078 00:36:49,160 --> 00:36:50,360 REGIONAL METASTASIS OR ANYTHING 1079 00:36:50,360 --> 00:36:52,160 ELSE OUTSIDE THE ABDOMINAL 1080 00:36:52,160 --> 00:36:52,400 CAVITY. 1081 00:36:52,400 --> 00:36:53,520 SOPHISTICATEDY WHEN YOU LOOK 1082 00:36:53,520 --> 00:36:56,040 STATISTICALLY AT THIS DAT ATHIS 1083 00:36:56,040 --> 00:36:57,840 PLAYS OUT, THAT IT'S VERY 1084 00:36:57,840 --> 00:36:59,280 CONSISTENT THAT THE STAGE 1 1085 00:36:59,280 --> 00:37:01,120 PATIENTS HAD A HUNDRED% 1086 00:37:01,120 --> 00:37:03,120 SURVIVAL, THE STAGE 2 PATIENTS, 1087 00:37:03,120 --> 00:37:05,280 70% SURVIVAL AND THE STAGE 3 AND 1088 00:37:05,280 --> 00:37:06,240 4 PATIENTS REFLECT MORE HIOF 1089 00:37:06,240 --> 00:37:07,280 THORICALLY OF WHAT THESE 1090 00:37:07,280 --> 00:37:11,480 PATIENTS LOOK LIKE PRIOR TO ME 1091 00:37:11,480 --> 00:37:15,000 STUDYING THIS DISEASE AND 1092 00:37:15,000 --> 00:37:15,800 STATISTICALLY SIGNIFICANT. 1093 00:37:15,800 --> 00:37:17,720 SO WITH THE MULTIVARIANT 1094 00:37:17,720 --> 00:37:19,280 ANALYSIS SHOWED US STAGE 3 OR 4 1095 00:37:19,280 --> 00:37:21,720 RISK OF PATIENTS WITH HIGHER 1096 00:37:21,720 --> 00:37:23,280 DEATH, PATIENTS WITHOUT EXTRA 1097 00:37:23,280 --> 00:37:25,800 ABDOMINAL DISEASE DOES WELL, AND 1098 00:37:25,800 --> 00:37:27,440 INCOMPLETE RESECTION PROMOTED A 1099 00:37:27,440 --> 00:37:29,360 HIGHER RISK FOR RECURRENCE AND 1100 00:37:29,360 --> 00:37:30,120 PATIENTS WITHOUT LIVER DISEASE 1101 00:37:30,120 --> 00:37:36,800 DID BETTER WITH PATIENTS WITH 1102 00:37:36,800 --> 00:37:37,800 LIVER DISEASE. 1103 00:37:37,800 --> 00:37:39,640 SO NOW ON TO THE SCIENCE OF WHAT 1104 00:37:39,640 --> 00:37:41,120 IS A TUMOR AND HOW DOES IT 1105 00:37:41,120 --> 00:37:41,520 OCCUR. 1106 00:37:41,520 --> 00:37:42,920 SO WHEN I FIRST SAW THESE TUMORS 1107 00:37:42,920 --> 00:37:44,600 AND I REMEMBER I MENTIONED THAT 1108 00:37:44,600 --> 00:37:46,480 THE TUMORS ARE ALWAYS STUCK TO 1109 00:37:46,480 --> 00:37:47,000 THE SEMINAL VESICLE. 1110 00:37:47,000 --> 00:37:54,560 SO I WAS GETTING VERY COG COGNT 1111 00:37:54,560 --> 00:37:56,400 OF THE PATTERN THAT EVERY 1112 00:37:56,400 --> 00:37:58,520 PATIENT I WAS DOING SURGERY ON, 1113 00:37:58,520 --> 00:38:01,640 I WAS CUTTING OFF TUMOR VESICLES 1114 00:38:01,640 --> 00:38:03,480 AND NIEBT% OF THE PATIENTS WERE 1115 00:38:03,480 --> 00:38:04,600 MAIL MALE. 1116 00:38:04,600 --> 00:38:07,200 SO I THOUGHT IF IT HAD AN 1117 00:38:07,200 --> 00:38:08,160 ANDROGEN COMPONENT TO IT SO THE 1118 00:38:08,160 --> 00:38:10,240 FIRST THING I DID WAS TAKE THE 1119 00:38:10,240 --> 00:38:11,280 CELLS INTO THE DID WEST OTHER 1120 00:38:11,280 --> 00:38:13,960 THAN BLOT TO LOOK AT PROTEINS 1121 00:38:13,960 --> 00:38:24,440 AND COMPARED THEM WITH TC71. 1122 00:38:27,720 --> 00:38:33,480 COMPARING DSRCT TO THE EWING'S 1123 00:38:33,480 --> 00:38:35,800 SARCOMA, BUT THE SAME AMOUNT OF 1124 00:38:35,800 --> 00:38:37,920 RECEPTOR IN PROSTATE CANCER IS 1125 00:38:37,920 --> 00:38:39,280 FOUND IN DSRCT, AND SO, I BEGAN 1126 00:38:39,280 --> 00:38:42,280 TO ASK WHAT IS THE ROLE OF THIS 1127 00:38:42,280 --> 00:38:43,640 RECEPTOR SINCE IT'S VERY HIGHLY 1128 00:38:43,640 --> 00:38:45,440 EXPRESSED THIS THESE TUMOR 1129 00:38:45,440 --> 00:38:47,920 CELLS. 1130 00:38:47,920 --> 00:38:49,400 SO I COMPARED DSRCT TO THE 1131 00:38:49,400 --> 00:38:50,920 CANCER CELLS IN THE LABORATORY 1132 00:38:50,920 --> 00:38:52,880 AND I GREEN COLOR STAINING FOR 1133 00:38:52,880 --> 00:38:54,480 ANDROGEN RECEPTOR AND IF YOU 1134 00:38:54,480 --> 00:38:56,000 LOOK AT THE COMPARISON BETWEEN 1135 00:38:56,000 --> 00:38:58,760 THE PROOF THEASTY CANCER CELLS 1136 00:38:58,760 --> 00:39:00,960 AND THE DSRCT CELLS YOU SEE 1137 00:39:00,960 --> 00:39:03,280 THERE'S A SIGNIFICANT EXPRESSION 1138 00:39:03,280 --> 00:39:05,960 IN THE DSRCT CELLS ALMOST AS 1139 00:39:05,960 --> 00:39:07,960 STRONG AS IN PROOF THEASTY 1140 00:39:07,960 --> 00:39:08,680 CANCERREN. 1141 00:39:08,680 --> 00:39:11,640 THEN I TOOK DSRCT CELLS AND 1142 00:39:11,640 --> 00:39:12,800 ADDED TESTOSTERONE TO THE CELL 1143 00:39:12,800 --> 00:39:14,480 CULTURE AND WATCHED THE CELLS 1144 00:39:14,480 --> 00:39:16,240 PROLIFERATE WITH INCREASING 1145 00:39:16,240 --> 00:39:18,520 DOSES OF TESTOSTERONE. 1146 00:39:18,520 --> 00:39:19,600 SIMILARLY FOR DISCIPLINARY 1147 00:39:19,600 --> 00:39:22,440 HYDROTESTOSTERONE, WHEN YOU 1148 00:39:22,440 --> 00:39:24,000 ADDED IT, THE RED LINE ACROSS 1149 00:39:24,000 --> 00:39:25,240 THE CANCER CELLS INCREASED. 1150 00:39:25,240 --> 00:39:27,920 THE BLUE LINE IS THE EWING 1151 00:39:27,920 --> 00:39:28,680 SARCOMA CELLS THAT DIDN'T CHANGE 1152 00:39:28,680 --> 00:39:31,320 AT ALL AND THE BLACK LINE IS THE 1153 00:39:31,320 --> 00:39:32,560 DSRCT CELLS THAT INCREASED AT 1154 00:39:32,560 --> 00:39:38,160 THE SAME SLOPE AS A PROSTATE 1155 00:39:38,160 --> 00:39:38,520 CANCER CELLS. 1156 00:39:38,520 --> 00:39:41,320 SO THEN I BEGAN TO LOOK AT THE 1157 00:39:41,320 --> 00:39:43,800 PATHWAYS THAT PROSTATE CANCER 1158 00:39:43,800 --> 00:39:45,000 CELL DEVELOPED AND METASTASIZED 1159 00:39:45,000 --> 00:39:47,200 AND LOOK AT RNA HEAT SEEKING 1160 00:39:47,200 --> 00:39:48,800 MAPS TO UNDERSTAND HOW SIMILAR, 1161 00:39:48,800 --> 00:39:55,840 OR DIFFERENT THEY ARE WITH 1162 00:39:55,840 --> 00:39:58,360 RECAST RATE RESISTANT PROSTATE 1163 00:39:58,360 --> 00:39:58,920 CANCER. 1164 00:39:58,920 --> 00:40:00,560 SO THEN THE QUESTION IS, AGAIN 1165 00:40:00,560 --> 00:40:01,880 WRRKS DOES IT COME FROM, SO WHEN 1166 00:40:01,880 --> 00:40:05,000 YOU START TO LOOK AT WHERE 1167 00:40:05,000 --> 00:40:06,120 TISSUE--TUMORS COME FROM, YOU 1168 00:40:06,120 --> 00:40:08,880 LOOK AT LIKE TISSUE AND LIKE 1169 00:40:08,880 --> 00:40:10,960 PATHWAYS TO SEE IF YOU CAN PIECE 1170 00:40:10,960 --> 00:40:12,560 TOGETHER WHAT IT MIGHT LOOK LIKE 1171 00:40:12,560 --> 00:40:14,920 IN DIFFERENT TUMORS AND 1172 00:40:14,920 --> 00:40:16,120 DIFFERENT TISSUES. 1173 00:40:16,120 --> 00:40:20,320 SO THE BLUE DOTS ARE DSRCT 1174 00:40:20,320 --> 00:40:24,440 TUMORS, THE OTHER DOTS ARE 1175 00:40:24,440 --> 00:40:24,960 DIFFERENT TISSUE TYPES. 1176 00:40:24,960 --> 00:40:27,800 SO THE BLUE TISSUE HERE IS THE 1177 00:40:27,800 --> 00:40:28,760 LUNG, THE SKELETAL MUSCLE AND 1178 00:40:28,760 --> 00:40:30,640 SKIN ARE DOWN HERE AND THE 1179 00:40:30,640 --> 00:40:31,480 PURPLE DOTS ARE FAT. 1180 00:40:31,480 --> 00:40:34,440 SO CAN YOU SEE THAT THE DSRCT 1181 00:40:34,440 --> 00:40:35,960 TUMORS LOOK CLOSER TO FAT THAN 1182 00:40:35,960 --> 00:40:37,440 ANYTHING ELSE BUT REALLY DON'T 1183 00:40:37,440 --> 00:40:39,400 LOOK LIKE ANY LITTLER TISSUE 1184 00:40:39,400 --> 00:40:40,920 TYPE, THEY DON'T LOOK LIKE FAT, 1185 00:40:40,920 --> 00:40:42,920 OR LUNG OR MUSCLE OR SKIN. 1186 00:40:42,920 --> 00:40:44,840 AND THIS PANEL TO THE RIGHT 1187 00:40:44,840 --> 00:40:46,600 SHOWS HOW DIFFERENT IT IS THAN 1188 00:40:46,600 --> 00:40:47,760 OTHER SARCOMAS, SO THESE ARE A 1189 00:40:47,760 --> 00:40:52,800 LIST OF OTHER SARCOMAS THAT 1190 00:40:52,800 --> 00:40:56,880 OCCUROT ABDOMINAL CAVITY. 1191 00:40:56,880 --> 00:40:57,960 CHOND ROW, DOLPS, AND OTHERS, 1192 00:40:57,960 --> 00:41:00,760 CAN YOU SEE THAT THE DSRCT 1193 00:41:00,760 --> 00:41:02,800 TUMORS CLUSTER WAY OVER HERE, 1194 00:41:02,800 --> 00:41:04,880 NOWHERE NEAR ANY SIMILARITY 1195 00:41:04,880 --> 00:41:07,840 GENETICALLY TO ANY OF THESE 1196 00:41:07,840 --> 00:41:08,520 OTHER TUMORS. 1197 00:41:08,520 --> 00:41:11,760 AND WHEN YOU TRY TO LOOK AT THE 1198 00:41:11,760 --> 00:41:12,640 GENEX TREE, YOU SLEEP APNEA AND 1199 00:41:12,640 --> 00:41:13,720 OBESITYY A DIFFERENT STORY AS 1200 00:41:13,720 --> 00:41:16,040 WELL, SO EVERY 1 OF MY PATIENTS 1201 00:41:16,040 --> 00:41:18,240 I TOOK TISSUE FROM THE IN THE 1202 00:41:18,240 --> 00:41:20,680 OPERATING ROOM AND TOOK IT TO 1203 00:41:20,680 --> 00:41:23,800 THE LAB RADIO LABORATORY, AND 1204 00:41:23,800 --> 00:41:27,440 THESE THE COMMONALITY, IN THIS 1205 00:41:27,440 --> 00:41:30,200 TREE, IS EWINGS T1 AT THE BASE 1206 00:41:30,200 --> 00:41:31,960 OF THE TREE SO TO SPEAK BUT WHEN 1207 00:41:31,960 --> 00:41:33,120 YOU BRANCH UP FROM THAT, YOU SEE 1208 00:41:33,120 --> 00:41:34,920 THAT ALL OF THESE PATIENTS HAVE 1209 00:41:34,920 --> 00:41:36,200 DIFFERENT TUMOR EXPRESSION, 1210 00:41:36,200 --> 00:41:36,960 DIFFERENT PROTEIN EXPRESSIONS, 1211 00:41:36,960 --> 00:41:38,640 WHICH AGAIN MAKE ITS VERY 1212 00:41:38,640 --> 00:41:43,440 DIFFICULT TO FIND COMMONALITIES, 1213 00:41:43,440 --> 00:41:44,640 IN THESE TUMORS. 1214 00:41:44,640 --> 00:41:48,320 SO, I NEED TO HAVE AN ORTHOTOPIC 1215 00:41:48,320 --> 00:41:49,720 XENOGRAFTIC MODEL AND RECRETE 1216 00:41:49,720 --> 00:41:50,920 THE DISEASE IN A MOUSE IN ORDER 1217 00:41:50,920 --> 00:41:52,400 TO STUDY IT BETTER SO KNOWING 1218 00:41:52,400 --> 00:41:55,640 WHAT I KNEW ABOUT THE PROSTATE 1219 00:41:55,640 --> 00:41:59,680 CANCER AND THE ANDROGEN 1220 00:41:59,680 --> 00:42:02,680 SENSITIVITY, THESE DSRCT CELLS 1221 00:42:02,680 --> 00:42:04,600 INTO THE PERITESTICULAR PERRY 1222 00:42:04,600 --> 00:42:07,280 AND THE PELVIC REGION OF IMMUNO 1223 00:42:07,280 --> 00:42:08,920 COMPROMISED, AND WE LABELED THEM 1224 00:42:08,920 --> 00:42:10,680 OF THE LUCIFERASE AND IMAGE THEM 1225 00:42:10,680 --> 00:42:13,560 AT 6 WEEKS AND THEN EVERY WEEK 1226 00:42:13,560 --> 00:42:13,880 AFTERWARDS. 1227 00:42:13,880 --> 00:42:17,800 AND THIS IS WHAT THE MODEL LOOKS 1228 00:42:17,800 --> 00:42:18,000 LIKE. 1229 00:42:18,000 --> 00:42:19,680 THE MICE THAT HAVE NO TUMOR, 1230 00:42:19,680 --> 00:42:21,320 THIS IS OUR CONTROL. 1231 00:42:21,320 --> 00:42:22,360 THIS IS 2 MILLION TUMOR CELLS 1232 00:42:22,360 --> 00:42:24,640 EACH AND THIS IS 5 MILLION EACH 1233 00:42:24,640 --> 00:42:25,720 IN THESE 2 MICE. 1234 00:42:25,720 --> 00:42:28,960 AND IF YOU LOOK AT THE NECROPSY, 1235 00:42:28,960 --> 00:42:30,640 IT DUPLICATES THE DISEASE VERY, 1236 00:42:30,640 --> 00:42:30,960 VERY CLOSELY. 1237 00:42:30,960 --> 00:42:34,200 SO THIS WHRIET DOT HERE IS ON 1238 00:42:34,200 --> 00:42:36,200 THE SEMINOLE VESICLE, THIS IS 1239 00:42:36,200 --> 00:42:37,400 SEMINOLE VESICLE OF THE MOUSE 1240 00:42:37,400 --> 00:42:38,720 AND ALL THESE WHITE DOTS AGAIN 1241 00:42:38,720 --> 00:42:40,360 ARE TUMORS IN THE ABDOMINAL 1242 00:42:40,360 --> 00:42:41,800 CAVITY OF THIS MOUSE AND IF YOU 1243 00:42:41,800 --> 00:42:43,200 LOOK CAREFULLY YOU CAN SEE 1 ON 1244 00:42:43,200 --> 00:42:44,200 THE SURFACE OF THE LIVER AND 1245 00:42:44,200 --> 00:42:46,560 ANOTHER 1 HERE AND WHEN YOU 1246 00:42:46,560 --> 00:42:47,200 LOOKED MICROSCOPICALLY AT 1247 00:42:47,200 --> 00:42:48,920 VARIOUS TISSUES AND THE NECROPSY 1248 00:42:48,920 --> 00:42:51,080 OF THIS MOUSE, YOU FIND THERE IS 1249 00:42:51,080 --> 00:42:51,760 ABNORMALITIES DIAGRAMINAL 1250 00:42:51,760 --> 00:42:52,720 METASTASIS, REMEMBER THE 1251 00:42:52,720 --> 00:42:54,600 PANCREAS AND THE MOUSE IS A FREE 1252 00:42:54,600 --> 00:42:57,880 FLOATING AND THERE'S TUMOR NEXT 1253 00:42:57,880 --> 00:42:58,800 TO THE PANCREAS. 1254 00:42:58,800 --> 00:42:59,640 AND SUPER [INDISCERNIBLE] 1255 00:42:59,640 --> 00:43:01,160 METASTASIS WHICH IS A VERY 1256 00:43:01,160 --> 00:43:01,920 TYPICAL PRESENTATION OF THIS 1257 00:43:01,920 --> 00:43:04,440 DISEASE, CAN YOU SEE THAT IN THE 1258 00:43:04,440 --> 00:43:05,040 MICE AS WELL. 1259 00:43:05,040 --> 00:43:08,120 SO THEN I WENT ON TO DO SINGLE 1260 00:43:08,120 --> 00:43:09,200 CELL SEQUENCING TO UNDERSTAND 1261 00:43:09,200 --> 00:43:11,480 EVEN MORE ABOUT THIS TUMOR 1262 00:43:11,480 --> 00:43:13,640 GROWTH IN THE CONTEXT OF THIS 1263 00:43:13,640 --> 00:43:14,600 MOUSE MODEL. 1264 00:43:14,600 --> 00:43:16,880 SO THESE ARE DSRCT TUMOR CELLS 1265 00:43:16,880 --> 00:43:18,240 FROM 2 DIFFERENT PATIENTS, THE 1266 00:43:18,240 --> 00:43:21,000 BLUE IS AT 1 PATIENT, GREEN IS A 1267 00:43:21,000 --> 00:43:21,640 DIFFERENT PATIENT. 1268 00:43:21,640 --> 00:43:23,080 AND YOU CAN SEE WE'RE ABLE TO 1269 00:43:23,080 --> 00:43:26,560 TAKE 1 LOCAL TUMOR AND SEPARATE 1270 00:43:26,560 --> 00:43:28,320 ALL THE DIFFERENT TUMORS TO SEE 1271 00:43:28,320 --> 00:43:30,480 THOSE CELLS SO WE CAN FOCUS ON 1272 00:43:30,480 --> 00:43:30,960 JUST THE TUMOR CELLS. 1273 00:43:30,960 --> 00:43:32,400 SO CAN YOU SEE THERE'S 1274 00:43:32,400 --> 00:43:34,480 POPULATIONS OF MONOCYTES AND 1275 00:43:34,480 --> 00:43:35,080 MACROPHAGES, NUTRIFILLS, ET 1276 00:43:35,080 --> 00:43:38,160 CETERA WITHIN THE TUMORS. 1277 00:43:38,160 --> 00:43:39,440 AGAIN, THESE 2 CIRCLES ARE 2 1278 00:43:39,440 --> 00:43:41,400 DIFFERENT PATIENTS AND WE BEING 1279 00:43:41,400 --> 00:43:42,880 LOAMACY THEA WT1 AND ANDROGEN 1280 00:43:42,880 --> 00:43:44,880 RECEPTOR AND YOU SEE THAT ONLY 1281 00:43:44,880 --> 00:43:48,040 THE TUMOR CELLS OF BOTH PATIENTS 1282 00:43:48,040 --> 00:43:49,240 STAINED WITH TK1 ANDROGEN 1283 00:43:49,240 --> 00:43:49,960 RECEPTOR AND THE SMALL 1284 00:43:49,960 --> 00:43:52,520 POPULATION HERE TO THE SIDE IS 1285 00:43:52,520 --> 00:43:54,720 WHAT WE'RE TERMING THE CANCER 1286 00:43:54,720 --> 00:43:56,280 STEM CELLS FOR DSRCT SO YOU CAN 1287 00:43:56,280 --> 00:43:58,400 SEE THAT THE STEM CELLS, THE 1288 00:43:58,400 --> 00:43:59,240 SMALLER POPULATION THAT DRIVE 1289 00:43:59,240 --> 00:44:02,440 THE TUMOR GROWTH AND METASTASIS, 1290 00:44:02,440 --> 00:44:04,600 COMMONLY STAINED WITH WT1 AND 1291 00:44:04,600 --> 00:44:07,480 ANGIO RECEPTOR. 1292 00:44:07,480 --> 00:44:08,880 WHEN YOU LOOK AT AGAIN THE 1293 00:44:08,880 --> 00:44:10,640 SUBSET OF CELLS IN THE CANCER 1294 00:44:10,640 --> 00:44:15,880 STEM CELL POPULATION, YOU HAVE 1295 00:44:15,880 --> 00:44:19,240 ANGIO RECEPTOR, SOX 2 IS ANOTHER 1296 00:44:19,240 --> 00:44:20,480 MARKER AND THOSE ARE ONLY 1297 00:44:20,480 --> 00:44:23,240 PRESSENT IN THE SMALL POPULATION 1298 00:44:23,240 --> 00:44:23,520 OF CELLS. 1299 00:44:23,520 --> 00:44:24,800 SO I WON'T WON'T GO THROUGH 1300 00:44:24,800 --> 00:44:25,760 EVERY SINGLE PIECE OF DATA YOU 1301 00:44:25,760 --> 00:44:26,880 ABOUT I WILL SHOW YOU HOW WE 1302 00:44:26,880 --> 00:44:27,920 LOOKEDDA THE THIS TREE. 1303 00:44:27,920 --> 00:44:30,920 SO WE DEVELOPED A GENETIC TREE 1304 00:44:30,920 --> 00:44:33,240 FROM THE INFORMATION THAT WE 1305 00:44:33,240 --> 00:44:35,320 ACHIEVE WITH THE RNA SEQUENCE. 1306 00:44:35,320 --> 00:44:37,040 WE MADE SURE THAT THE CELLS WERE 1307 00:44:37,040 --> 00:44:40,360 PURE AND SO THIS JUST IS A 1308 00:44:40,360 --> 00:44:42,400 DOCUMENTATION OF THE RNA PURITY 1309 00:44:42,400 --> 00:44:44,880 AND THE PERCENT IN EACH SAMPLE. 1310 00:44:44,880 --> 00:44:47,200 THEN WE LOOKED AT THE DIFFERENT 1311 00:44:47,200 --> 00:44:48,440 PORTIONS OF THE TREE, THE 1312 00:44:48,440 --> 00:44:50,080 DIFFERENT CELLS AND WHAT 1313 00:44:50,080 --> 00:44:51,280 PROTEINS WERE EXPRESSED AND WHAT 1314 00:44:51,280 --> 00:44:52,320 GENES ARE IMRESESSED IN THOSE 1315 00:44:52,320 --> 00:44:54,280 CELLS AND TO LOOK AT IT MORE 1316 00:44:54,280 --> 00:44:55,840 CLOSELY SEE YOU CAN SEE IT 1317 00:44:55,840 --> 00:44:58,320 BETTER, THESE ARE THE DIFFERENT 1318 00:44:58,320 --> 00:45:00,920 CELL TYPES THAT WERE CIRCLES IN 1319 00:45:00,920 --> 00:45:02,240 THE SINGLE CELL SEQUENCING AND 1320 00:45:02,240 --> 00:45:04,120 THE GENETIC PANEL THAT RESULTED 1321 00:45:04,120 --> 00:45:05,040 FROM THE DIFFERENT CELL TYPES 1322 00:45:05,040 --> 00:45:06,400 AND WE TOOK THAT AND BROKE THAT 1323 00:45:06,400 --> 00:45:08,840 DOWN INTO WHAT WE WAS MOST 1324 00:45:08,840 --> 00:45:12,520 COMMONLY UP OR DOWN REGULATED 1325 00:45:12,520 --> 00:45:15,480 AND NARROWED IT DOWN TO THIS 1326 00:45:15,480 --> 00:45:16,160 GROUP OF GENES. 1327 00:45:16,160 --> 00:45:18,800 SO WE KNEW ABOUT WT1, WE KNEW 1328 00:45:18,800 --> 00:45:22,400 ABOUT ANGIO RECEPTOR, WE DIDN'T 1329 00:45:22,400 --> 00:45:24,240 KNOW ABOUT JJB2, WHICH IS WHAT 1330 00:45:24,240 --> 00:45:26,760 I'M LOOKING FORWARD FOR NOW IN 1331 00:45:26,760 --> 00:45:27,280 THE LABORATORY. 1332 00:45:27,280 --> 00:45:29,120 AND THIS IS A DIFFERENT COUNT OF 1333 00:45:29,120 --> 00:45:30,960 DIFFERENT GENES IN THE 1334 00:45:30,960 --> 00:45:31,960 SUBPOPULATIONS 1-12 OF THE 1335 00:45:31,960 --> 00:45:34,000 CIRCLES OF THE CANCER STEM 1336 00:45:34,000 --> 00:45:34,200 CELLS. 1337 00:45:34,200 --> 00:45:36,440 EXCUSE ME OF THE SINGLE CELL 1338 00:45:36,440 --> 00:45:37,480 SEQUENCING. 1339 00:45:37,480 --> 00:45:39,320 THEN WE WENT ON TO LOOK AT 1340 00:45:39,320 --> 00:45:42,560 PATIENT SAMPLES AND THE SHARED 1341 00:45:42,560 --> 00:45:43,800 GENETICS THAT WERE ANDROGEN 1342 00:45:43,800 --> 00:45:44,080 DEPEBDENT. 1343 00:45:44,080 --> 00:45:47,560 SO NOW WE'RE JUST LOOKING AT 1344 00:45:47,560 --> 00:45:48,760 ANDROGEN RECEPTOR DEPENDENT 1345 00:45:48,760 --> 00:45:49,360 PROTEINS AND GENES. 1346 00:45:49,360 --> 00:45:51,280 SO THESE ARE TUMORS FROM MY ISHT 1347 00:45:51,280 --> 00:45:52,600 PATHWAY GIVESS, THIS IS 1348 00:45:52,600 --> 00:45:55,360 14-EXCUSE ME DIFFERENT PATIENTS 1349 00:45:55,360 --> 00:45:57,200 COMPARED TO 6 DIFFERENT EWING 1350 00:45:57,200 --> 00:45:59,040 SARCOMA PATIENTS AND THIS SET OF 1351 00:45:59,040 --> 00:46:01,840 EXPERIMENTS SHOW THE PROTEIN 1352 00:46:01,840 --> 00:46:05,880 EXPRESSION IN THE DSRCT IN RED 1353 00:46:05,880 --> 00:46:07,440 VERSUS EWING SARCOMA IN BLUE. 1354 00:46:07,440 --> 00:46:09,280 SO YOU CAN SEE THE TUMORS 1355 00:46:09,280 --> 00:46:11,280 WHETHER YOU LOOK AT ANGIO 1356 00:46:11,280 --> 00:46:12,720 RECEPTOR OR OTHER 3 PROTEINS 1357 00:46:12,720 --> 00:46:17,200 HAVE A SIGNIFICANTLY HIGHER 1358 00:46:17,200 --> 00:46:18,560 EXPRESSION THAN EWING SARCOMA 1359 00:46:18,560 --> 00:46:20,800 TUMORS BUT THAT THESE TALENTS, 1360 00:46:20,800 --> 00:46:22,200 PROBABLY BECAUSE THEY CROSS THE 1361 00:46:22,200 --> 00:46:25,000 0 LINE MAY NOT BE EFFECTIVE 1362 00:46:25,000 --> 00:46:26,600 TARGETS SO ANGIO RECEPTOR LOOKS 1363 00:46:26,600 --> 00:46:27,920 LIKE IT'S STILL FALLING OUT AS 1364 00:46:27,920 --> 00:46:29,440 THE MOST EFFECTIVE TARGET AND WE 1365 00:46:29,440 --> 00:46:32,760 LOOKED AT THESE GENES HERE AND 1366 00:46:32,760 --> 00:46:34,480 THEIR EXPRESSION IN DSRCT 1367 00:46:34,480 --> 00:46:37,080 PATIENT TUMORS IN EWING SARCOMA, 1368 00:46:37,080 --> 00:46:38,160 COMPARING THE TUMORS AND FOUND 1369 00:46:38,160 --> 00:46:40,480 THE SAME THING, THAT THE RED 1370 00:46:40,480 --> 00:46:41,920 DSRCT PATIENTS HAVE MUCH HIGHER 1371 00:46:41,920 --> 00:46:43,000 EXPRESSION OF THESE 2 COMPARED 1372 00:46:43,000 --> 00:46:44,240 TO THE GENE. 1373 00:46:44,240 --> 00:46:47,560 SO WE'RE CONCENTRATING AGAIN ON 1374 00:46:47,560 --> 00:46:48,600 ANDROGEN RECEPTOR WHICH IS 1375 00:46:48,600 --> 00:46:51,720 LITTLE TO NONE IN THE EWING 1376 00:46:51,720 --> 00:46:52,080 SARCOMA GENE. 1377 00:46:52,080 --> 00:46:57,280 SO THIS IS THE MOST RECENT 1378 00:46:57,280 --> 00:46:58,360 PUBLICATION FROM NATURE, AND I 1379 00:46:58,360 --> 00:47:00,200 WANT YOU TO FOCUS ON THESE 2 1380 00:47:00,200 --> 00:47:02,280 COLUMNS IN THIS WAY. 1381 00:47:02,280 --> 00:47:05,440 SO THESE--THIS LEFT COLUMN IS A 1382 00:47:05,440 --> 00:47:07,640 XEEN O GRAPH MODEL, AND IN THE 1383 00:47:07,640 --> 00:47:10,080 RIGHT COLUMN OR PDXs OR 1384 00:47:10,080 --> 00:47:11,520 PATIENT DERIVED XEEN O GRAPHS SO 1385 00:47:11,520 --> 00:47:13,120 TAKEN THE CELLS FROM THE PATIENT 1386 00:47:13,120 --> 00:47:14,600 TUMOR WE TAKE A CHUNK OF TUMOR 1387 00:47:14,600 --> 00:47:16,640 IS PUT IT INTO THE MICE. 1388 00:47:16,640 --> 00:47:18,720 AND THE DARK ORANGE, FOCUS ON 1389 00:47:18,720 --> 00:47:24,920 THE DARK ORANGE LINE WHICH IS 1390 00:47:24,920 --> 00:47:26,960 THE ANTISENSE, SO MY 1391 00:47:26,960 --> 00:47:29,240 COLLABORATORS MADE AN ANTISENSE 1392 00:47:29,240 --> 00:47:32,200 WITH THE TUMOR AND WE COMPARED 1393 00:47:32,200 --> 00:47:33,960 THE TREATMENT IN THE MICE AND IN 1394 00:47:33,960 --> 00:47:38,000 THE PD ACCESS TO TREATMENT OF 1395 00:47:38,000 --> 00:47:43,880 PROSTATE CANCER SO ENZALUTAMIDE 1396 00:47:43,880 --> 00:47:50,280 IS A CONTRIBUTOR TO PREVENTION 1397 00:47:50,280 --> 00:47:50,720 OF PROSTATE CANCER. 1398 00:47:50,720 --> 00:47:53,520 SO IN ALL THE ANIMALS YOU CAN 1399 00:47:53,520 --> 00:47:55,840 SEE WHEN WE USE ANTISENSE, THEY 1400 00:47:55,840 --> 00:47:57,120 TUMORS DIDN'T GROW, THE GROWTH 1401 00:47:57,120 --> 00:48:06,160 OF THE TUMOR WAS SLOWER, THAN IN 1402 00:48:06,160 --> 00:48:08,200 THE ENZALUTAMIDE, AND IN THE PDX 1403 00:48:08,200 --> 00:48:10,960 NODDLE THE SAME THING, THE DORK 1404 00:48:10,960 --> 00:48:12,960 ORANGE, THE GROWTH OF THE TUMOR 1405 00:48:12,960 --> 00:48:13,600 VOLUNTEERS UMKC WAS LOWER, THE 1406 00:48:13,600 --> 00:48:15,520 GROWTH OF THE TUMOR WAS SLOWER 1407 00:48:15,520 --> 00:48:17,560 AND IN FACT SPHARTED TO DECREASE 1408 00:48:17,560 --> 00:48:19,280 AT THE END OF THE STUDY, AND 1409 00:48:19,280 --> 00:48:20,480 THERE WAS A HUNDRED% SURVIVAL 1410 00:48:20,480 --> 00:48:22,200 COMPARED TO SOME OR MOST OF ALL 1411 00:48:22,200 --> 00:48:25,000 OF THE OTHER MICE DYING, EXTEN O 1412 00:48:25,000 --> 00:48:27,120 GRAPH AND THE PDX MODELS. 1413 00:48:27,120 --> 00:48:28,320 SO IN CONCLUSION, IT IS POSSIBLE 1414 00:48:28,320 --> 00:48:30,240 TO GO FROM BENCH TO BEDSIDE. 1415 00:48:30,240 --> 00:48:32,360 IT IS POSSIBLE TO UNDERSTAND A 1416 00:48:32,360 --> 00:48:35,560 DISEASE THAT WAS NOT PREVIOUSLY 1417 00:48:35,560 --> 00:48:36,560 TREATABLE OR UNDERSTOOD. 1418 00:48:36,560 --> 00:48:39,800 AND THAT PERSISTENCE AND 1419 00:48:39,800 --> 00:48:41,160 PATIENCE ARE KEY AND THIS IS THE 1420 00:48:41,160 --> 00:48:42,520 GREEN AT HOWARD IN THE 1421 00:48:42,520 --> 00:48:44,040 BACKGROUND OF MY SLIDES AS WELL 1422 00:48:44,040 --> 00:48:45,680 AS MY VIRTUAL BACKGROUND SO I 1423 00:48:45,680 --> 00:48:47,160 WANT TO THANK YOU VERY MUCH FOR 1424 00:48:47,160 --> 00:48:48,040 YOUR ATTENTION AND GIVE THANKS 1425 00:48:48,040 --> 00:48:50,040 TO THE PERSONS WHO HELPED ME 1426 00:48:50,040 --> 00:48:50,480 ALONG THE WAY. 1427 00:48:50,480 --> 00:48:59,960 THANK YOU SO MUCH. 1428 00:48:59,960 --> 00:49:03,760 >>THANK YOU SO MUCH 1429 00:49:03,760 --> 00:49:05,920 DR. HAYES DIXON ON THIS VERY 1430 00:49:05,920 --> 00:49:07,160 RARE TUMOR TYPE AND LAWEDDER 1431 00:49:07,160 --> 00:49:09,160 DALE YOU'VE DONE SO FAR TO MOVE 1432 00:49:09,160 --> 00:49:12,360 THIS FIELD FORWARD AND LEARN 1433 00:49:12,360 --> 00:49:12,880 ABOUT THIS TUMOR. 1434 00:49:12,880 --> 00:49:14,280 IT'S OPEN FOR QUESTIONS FOR 1435 00:49:14,280 --> 00:49:16,000 THOSE WHO HAVE ANY QUESTIONS, 1436 00:49:16,000 --> 00:49:18,680 YOU CAN PUT IT AGAIN THROUGH AT 1437 00:49:18,680 --> 00:49:21,280 THE BOTTOM OF YOUR SCREEN, BUT 1438 00:49:21,280 --> 00:49:23,040 BEFORE WE HAVE ANY--WHILE PEOPLE 1439 00:49:23,040 --> 00:49:27,040 ARE STILL BRINGS QUESTIONS, FOR 1440 00:49:27,040 --> 00:49:29,560 THIS RARE TUMOR TYPE I KNOW YOU 1441 00:49:29,560 --> 00:49:31,400 TALKED ABOUT DEVELOPING THE 1442 00:49:31,400 --> 00:49:35,880 MOUSE MODEL WHICH IS VERY 1443 00:49:35,880 --> 00:49:36,800 IMPORTANT BECAUSE FOR CHILDREN, 1444 00:49:36,800 --> 00:49:38,560 YOU DO NEED A MODEL BECAUSE YOU 1445 00:49:38,560 --> 00:49:42,200 CAN'T ALWAYS DO SOME OF 1446 00:49:42,200 --> 00:49:43,320 THESE--TEST THESE THINGS ON 1447 00:49:43,320 --> 00:49:43,560 CHILDREN. 1448 00:49:43,560 --> 00:49:45,440 SO IT'S IMPORTANT TO UNDERSTAND 1449 00:49:45,440 --> 00:49:47,560 THE BIOLOGY THROUGH THESE 1450 00:49:47,560 --> 00:49:48,960 PRECLINNAL MODELS: 1451 00:49:48,960 --> 00:49:51,960 HAVE YOU EVER THOUGHT OF DOING 1452 00:49:51,960 --> 00:49:54,160 HIPEC IN YOUR MICE MODELS TO SEE 1453 00:49:54,160 --> 00:50:00,040 IF THERE'S A RESPONSE TO 1454 00:50:00,040 --> 00:50:01,560 ANDROGEN RECEPTOR OR ANTAGONIST 1455 00:50:01,560 --> 00:50:02,080 YOU TALKED ABOUT. 1456 00:50:02,080 --> 00:50:05,360 AND DO YOU KNOW OF ANY SAY, 1457 00:50:05,360 --> 00:50:08,080 EXVIVO MODELS THAT PROVIDE MORE 1458 00:50:08,080 --> 00:50:10,640 INSIGHT TO WHAT YOU'RE LOOKING 1459 00:50:10,640 --> 00:50:10,920 INTO. 1460 00:50:10,920 --> 00:50:12,240 WELL, THANK YOU FOR THAT 1461 00:50:12,240 --> 00:50:12,520 QUESTION. 1462 00:50:12,520 --> 00:50:16,000 CAN YOU HEAR ME OKAY? 1463 00:50:16,000 --> 00:50:17,000 ALL RIGHT. 1464 00:50:17,000 --> 00:50:17,640 >>I CAN HEAR YOU. 1465 00:50:17,640 --> 00:50:18,000 >>ALL RIGHT. 1466 00:50:18,000 --> 00:50:21,000 IT WOULD BE HELPFUL TO ACTUALLY 1467 00:50:21,000 --> 00:50:22,640 RECREATE HIPEC IN AN ANIMAL 1468 00:50:22,640 --> 00:50:23,720 MODEL AND THERE ARE RESEARCHERS 1469 00:50:23,720 --> 00:50:25,040 WHO ARE DOING SO, WHAT I'M 1470 00:50:25,040 --> 00:50:28,160 HOPING TO DO BEFORE I DO THAT IS 1471 00:50:28,160 --> 00:50:29,240 TO IDENTIFY SOME NOVEL DRUG 1472 00:50:29,240 --> 00:50:33,680 TARGETS WE CAN USE IN THE PIPE O 1473 00:50:33,680 --> 00:50:35,880 THERMOGENESISSIC CHEMO THERAPY 1474 00:50:35,880 --> 00:50:36,240 INFUSION. 1475 00:50:36,240 --> 00:50:38,240 ONE OF THE NUMBER OF GENES AND 1476 00:50:38,240 --> 00:50:39,520 PROTEINS I SHOWED IN THE LAST 1477 00:50:39,520 --> 00:50:40,600 COUPLE OF SLIDES, I WANT TO KNOW 1478 00:50:40,600 --> 00:50:42,120 IF WE CAN DEVELOP A NEW DRUG 1479 00:50:42,120 --> 00:50:44,760 THAT WILL SPECIFICALLY TARGET 1480 00:50:44,760 --> 00:50:44,960 THAT. 1481 00:50:44,960 --> 00:50:47,960 THE ANTISENSE THAT MY 1482 00:50:47,960 --> 00:50:48,560 COLLABORATOR, [INDISCERNIBLE] 1483 00:50:48,560 --> 00:50:51,280 MADE IS NOT SOMETHING THAT'S 1484 00:50:51,280 --> 00:50:52,360 IMMEDIATELY TRANSLATABLE TO A 1485 00:50:52,360 --> 00:50:54,600 DRUG AND SO, WE'VE GOT TO FIND 1486 00:50:54,600 --> 00:50:56,000 THAT PLUS OTHER TARGETS TO 1487 00:50:56,000 --> 00:50:58,000 DEVELOP AND ONCE WE GET THAT, I 1488 00:50:58,000 --> 00:51:00,680 THINK I WILL TRY DOING THE HIPEC 1489 00:51:00,680 --> 00:51:03,240 IN THE MICE THEMSELVES. 1490 00:51:03,240 --> 00:51:05,040 BUT THE OTHER POINT IS THAT 1491 00:51:05,040 --> 00:51:06,880 THERE MAY BE A SMARTER WAY TO DO 1492 00:51:06,880 --> 00:51:11,400 THINGS AS FAR AS INSTEAD OF 1493 00:51:11,400 --> 00:51:12,560 INFUSING HOT CHEMO THERAPY OVER 1494 00:51:12,560 --> 00:51:14,720 AN HOUR AND A HALF, MAYBE 1495 00:51:14,720 --> 00:51:16,640 THERE'S AN IMPLANT WE COULD PUT 1496 00:51:16,640 --> 00:51:18,160 INSIDE THE ABDOMINAL CAVITY THAT 1497 00:51:18,160 --> 00:51:21,040 WILL SLOWLY RELEASE CHEMO 1498 00:51:21,040 --> 00:51:22,360 THERAPY OR SOME TYPE OF DRUGS 1499 00:51:22,360 --> 00:51:24,960 OVER DAYS TO WEEKS, THAT WILL 1500 00:51:24,960 --> 00:51:26,480 ALLOW THE PATIENT NOT TO HAVE TO 1501 00:51:26,480 --> 00:51:28,120 BE SUBJECT TO THAT. 1502 00:51:28,120 --> 00:51:30,760 SO I'M LOOKING AT OTHER 1503 00:51:30,760 --> 00:51:33,520 ALTERNATIVES, I'M NOT BEING 1504 00:51:33,520 --> 00:51:35,360 NARROW MINDED ABOUT HIPEC BUT 1505 00:51:35,360 --> 00:51:42,120 OTHER WAY FOR CELL DEATH AT THE 1506 00:51:42,120 --> 00:51:43,280 MICROSCOPIC LEVEL. 1507 00:51:43,280 --> 00:51:53,560 >>THANK YOU. 1508 00:51:54,160 --> 00:51:55,160 >>I DON'T SEE ANY QUESTIONS IN 1509 00:51:55,160 --> 00:51:55,960 THE CHAT RIGHT NOW. 1510 00:51:55,960 --> 00:51:57,080 >>I DON'T SEE IT AS WELL. 1511 00:51:57,080 --> 00:52:00,040 BUT JUST AS A FOLLOW UP TO 1512 00:52:00,040 --> 00:52:02,120 LOOKING NOT JUST AT THE MODEL 1513 00:52:02,120 --> 00:52:04,880 BUT THE TUMOR BIOLOGY, HAVE YOU 1514 00:52:04,880 --> 00:52:07,480 NOTED ANY DIFFERENCES IN THE 1515 00:52:07,480 --> 00:52:11,840 BIOLOGY AS YOU SAID STAGE 1 1516 00:52:11,840 --> 00:52:13,840 VERSUS MORE ADVANCED BECAUSE AS 1517 00:52:13,840 --> 00:52:16,000 YOU SAID, THEY DEFINITELY HAVE 1518 00:52:16,000 --> 00:52:16,920 DIFFERENT MUTATIONAL STATUSES 1519 00:52:16,920 --> 00:52:18,720 WITHIN THE DIFFERENT TUMORS 1520 00:52:18,720 --> 00:52:21,760 WHICH MAKES IT DIFFICULT TO 1521 00:52:21,760 --> 00:52:22,480 TARGET THAT HETEROGENERATED AITY 1522 00:52:22,480 --> 00:52:23,800 MAKES IT DIFFICULT TO TARGET BUT 1523 00:52:23,800 --> 00:52:24,960 HAVE YOU NOTICED ANY 1524 00:52:24,960 --> 00:52:26,560 SIMILARITIES BETWEEN THOSE WHO 1525 00:52:26,560 --> 00:52:30,080 HAVE THE MORE FAVORABLE OUTCOME 1526 00:52:30,080 --> 00:52:31,520 VERSUS THOSE THAT DON'T. 1527 00:52:31,520 --> 00:52:32,920 >>I'M HOPING TO LOOK AT THAT 1528 00:52:32,920 --> 00:52:34,200 MOVING FORWARD, I HAVEN'T HAD A 1529 00:52:34,200 --> 00:52:36,280 CHANCE TO DO THAT JUST YET. 1530 00:52:36,280 --> 00:52:39,680 YOU NEED QUITE A FEW PATIENT 1531 00:52:39,680 --> 00:52:41,000 SAMPLES TO COMPARE 1 TO OTHER 1532 00:52:41,000 --> 00:52:42,280 AND SINCE IT'S SUCH A RARE 1533 00:52:42,280 --> 00:52:43,760 DISEASE, IT TAKES YEARS TO GET 1534 00:52:43,760 --> 00:52:44,800 ALL THE SAMPLES. 1535 00:52:44,800 --> 00:52:46,440 BUT YES, IT'S DEFINITELY 1536 00:52:46,440 --> 00:52:47,120 SOMETHING ON MYRA DART--DARTH TO 1537 00:52:47,120 --> 00:52:48,520 LOOK AT THE STAGE 1 PATIENTS AND 1538 00:52:48,520 --> 00:52:51,640 COMPARE THEM TO THE OTHER 1539 00:52:51,640 --> 00:52:52,080 PATIENTS. 1540 00:52:52,080 --> 00:52:53,520 THE OTHER COMMONALITY IN THE 1541 00:52:53,520 --> 00:52:55,240 STAGE 1 PATIENTS IS THEY ALL 1542 00:52:55,240 --> 00:52:59,280 HAVE DISEASE IN THE OMENTEM, SO 1543 00:52:59,280 --> 00:53:01,360 THE OTHER SORT OF IDEA THAT I'M 1544 00:53:01,360 --> 00:53:03,200 WORKING THROUGH IS HOW MUCH THE 1545 00:53:03,200 --> 00:53:05,040 OMENTUM PLAYS A ROLE IN THE 1546 00:53:05,040 --> 00:53:08,000 CONTROL OF THIS DISEASE OR THE 1547 00:53:08,000 --> 00:53:09,800 DISSEMINATION OF THIS DISEASE. 1548 00:53:09,800 --> 00:53:13,840 IT SEEMS LIKE THE OMENTA MIGHT 1549 00:53:13,840 --> 00:53:15,960 BE THE FIRST ORGAN OF ORIGIN 1550 00:53:15,960 --> 00:53:19,280 THAT IT MAY BE BECAUSE OF 1551 00:53:19,280 --> 00:53:22,400 GRAVITY THAT THE OMENTUM IS DOWN 1552 00:53:22,400 --> 00:53:25,840 IN THE PELVIS TOUCHING THE IT 1553 00:53:25,840 --> 00:53:27,240 WITH THE CELLS, I DON'T KNOW 1554 00:53:27,240 --> 00:53:28,760 IT'S A HYPOTHESIS RIGHT NOW BI I 1555 00:53:28,760 --> 00:53:30,760 THINK WE NEED MORE MORE TISSUE 1556 00:53:30,760 --> 00:53:32,440 FROM PATIENTS THAT ARE EARLY 1557 00:53:32,440 --> 00:53:34,520 STAGE DISEASE TO COMPARE THEM TO 1558 00:53:34,520 --> 00:53:36,880 LATER STAGES. 1559 00:53:36,880 --> 00:53:37,360 UNFORTUNATELY THERE'S 1560 00:53:37,360 --> 00:53:39,080 ONLY--THERE'S NO COMMERCIAL CELL 1561 00:53:39,080 --> 00:53:41,280 LINES FOR DSRCT WHICH ADDS AN 1562 00:53:41,280 --> 00:53:42,000 ADDITIONAL CHALLENGE. 1563 00:53:42,000 --> 00:53:43,320 SO YOU HAVE TO GET PATIENT 1564 00:53:43,320 --> 00:53:44,720 TUMORS TO STUDY IT. 1565 00:53:44,720 --> 00:53:46,440 THERE'S 1 CELL LINE THAT THE 1 I 1566 00:53:46,440 --> 00:53:48,840 WAS STUDYING THAT I BORROWED 1567 00:53:48,840 --> 00:53:50,720 FROM AN INVESTIGATOR IN JAPAN, 1568 00:53:50,720 --> 00:53:52,600 BUT THERE'S NO OTHER CELL LINES 1569 00:53:52,600 --> 00:53:54,640 IN THE WORLD RIGHT NOW TO STUDY 1570 00:53:54,640 --> 00:53:55,360 THIS DISEASE. 1571 00:53:55,360 --> 00:54:04,360 SO WE NEED SOME MORE PATIENT 1572 00:54:04,360 --> 00:54:05,280 TISSUES. 1573 00:54:05,280 --> 00:54:08,360 >>WE HAVE 1 REQUESTY THAT CAME 1574 00:54:08,360 --> 00:54:11,440 IN, WOULD YOU COMEBT ON THE 1575 00:54:11,440 --> 00:54:13,600 MOLECULAR GENETICS OF DSRCT? 1576 00:54:13,600 --> 00:54:14,240 >>WELL THE ONLY TECHNOLOGY 1577 00:54:14,240 --> 00:54:17,080 TRANSFER WE KNOW IS THE EWTS E1 1578 00:54:17,080 --> 00:54:18,840 FUSION GENE THAT,'S WHATY WOO 1579 00:54:18,840 --> 00:54:20,720 KNOW AND THEN THE PROTEINS I'M 1580 00:54:20,720 --> 00:54:22,840 LOOKING AT THROUGH THE SINGLE 1581 00:54:22,840 --> 00:54:26,480 CELL SEQUENCING SERIES, SO THE 1582 00:54:26,480 --> 00:54:27,880 PDGF RECEPTOR ALPHA IS 1 OF THE 1583 00:54:27,880 --> 00:54:31,120 TOP 1S AND BYS6 IS ANOTHER 1. 1584 00:54:31,120 --> 00:54:32,440 SO, I'M STILL WORKING THROUGH 1585 00:54:32,440 --> 00:54:37,160 WHICH THAT IS, WE DO KNOW 1586 00:54:37,160 --> 00:54:38,360 GENETICALLY THAT--NOT 1587 00:54:38,360 --> 00:54:39,440 GENETICALLY IMMUNOLOGICALLY THAT 1588 00:54:39,440 --> 00:54:41,160 DSRCT IS IMMUNE COLD AND SO WE 1589 00:54:41,160 --> 00:54:42,840 CAN'T USE OUR WONDERFUL NEW 1590 00:54:42,840 --> 00:54:44,600 IMMUNE THERAPY DRUGS THAT WE 1591 00:54:44,600 --> 00:54:45,760 HAVE FOR OTHER CANCERS, IT JUST 1592 00:54:45,760 --> 00:54:47,200 DOESN'T WORK ON THAT TUMOR SO A 1593 00:54:47,200 --> 00:54:56,640 LOT MORE WORK TO DO. 1594 00:54:56,640 --> 00:54:58,840 >>NO OTHER QUESTIONS, ALL 1595 00:54:58,840 --> 00:54:59,240 RIGHT? 1596 00:54:59,240 --> 00:54:59,600 >>DEFINITELY. 1597 00:54:59,600 --> 00:55:02,520 >>WELL I HOPE THAT WAS REALLY 1598 00:55:02,520 --> 00:55:03,360 HELPFUL TO EVERYONE. 1599 00:55:03,360 --> 00:55:04,120 >>ONE MORE QUESTION. 1600 00:55:04,120 --> 00:55:06,400 ONE MORE QUESTION. 1601 00:55:06,400 --> 00:55:06,720 >>OKAY. 1602 00:55:06,720 --> 00:55:09,800 >>SOMEONE SAID GREAT TALK, I 1603 00:55:09,800 --> 00:55:10,640 REMEMBER DR. HAYES DIXON SHOWING 1604 00:55:10,640 --> 00:55:12,640 A TUMOR SECTION IN THE GIRL IN 1605 00:55:12,640 --> 00:55:14,040 KENYA, WHAT OTHER GROABAL TUMOR 1606 00:55:14,040 --> 00:55:16,880 RESECTIONS HAVE YOU DONE FOR 1607 00:55:16,880 --> 00:55:17,720 THIS DSRCT? 1608 00:55:17,720 --> 00:55:19,480 >>THAT'S THE ONLY CASE I DID. 1609 00:55:19,480 --> 00:55:20,800 IT WAS QUITE CHALLENGING TO DO 1610 00:55:20,800 --> 00:55:22,240 THAT IN A COUNTRY THAT'S YOU 1611 00:55:22,240 --> 00:55:23,720 SHOULD RESOURCED BUT I'M NOT 1612 00:55:23,720 --> 00:55:25,360 OPPOSED TO DO IT AGAIN. 1613 00:55:25,360 --> 00:55:26,720 I THINK THAT, IN THAT PARTICULAR 1614 00:55:26,720 --> 00:55:28,200 CASE THAT CHILD AND THEIR FAMILY 1615 00:55:28,200 --> 00:55:28,960 COULDN'T TRAVEL TO THE UNITED 1616 00:55:28,960 --> 00:55:32,680 STATES AND SO I WENT THERE TO 1617 00:55:32,680 --> 00:55:33,680 HELP HER. 1618 00:55:33,680 --> 00:55:34,840 THERE ARE OTHER CHALLENGES. 1619 00:55:34,840 --> 00:55:36,440 YOU KNOW SOME OF THE PLACES 1620 00:55:36,440 --> 00:55:39,760 DON'T HAVE BLOOD BANKS, IT'S 1621 00:55:39,760 --> 00:55:42,480 DIFFICULT TO DO SURGERY WITHOUT 1622 00:55:42,480 --> 00:55:43,640 BLOOD AVAILABLE, SIMPLE THINGS 1623 00:55:43,640 --> 00:55:46,840 THAT WE TAKE FOR GRANTED LIKE 1624 00:55:46,840 --> 00:55:49,560 SUCTION AND CAUTERY ARE ARE 1625 00:55:49,560 --> 00:55:50,160 SPARSELY AVAILABLE AS WELL AS 1626 00:55:50,160 --> 00:55:51,800 SOME OF THE THINGS, LITTLER 1627 00:55:51,800 --> 00:55:53,680 THINGS WE TAKE FOR GRANTED LIKE 1628 00:55:53,680 --> 00:55:55,200 SUTURE AND TUBES AND DRAINS THAT 1629 00:55:55,200 --> 00:55:57,520 THEY JUST DON'T HAVE AVAILABLE 1630 00:55:57,520 --> 00:55:58,160 IN THOSE COUNTRIES. 1631 00:55:58,160 --> 00:56:01,400 DOESN'T MEAN IT CAN BE DONE, IT 1632 00:56:01,400 --> 00:56:02,360 JUST TAKES PLANNING AND THOUGHT 1633 00:56:02,360 --> 00:56:04,000 AND COMMITMENT BY THE PERSONS 1634 00:56:04,000 --> 00:56:11,640 THERE ON THE GROUND. 1635 00:56:11,640 --> 00:56:17,960 >>I SEE, NO FURTHER QUESTIONS. 1636 00:56:17,960 --> 00:56:19,280 THIS IS AGAIN, VERY EVOLVING 1637 00:56:19,280 --> 00:56:20,480 FIELD WHICH IS VERY EXCITING TO 1638 00:56:20,480 --> 00:56:22,120 SEE WHAT YOU ARE DOING AND WILL 1639 00:56:22,120 --> 00:56:25,280 CONTINUE TO DO AS YOU DEVELOP 1640 00:56:25,280 --> 00:56:28,600 MORE MODELS AND UNDERSTAND THE 1641 00:56:28,600 --> 00:56:29,320 DISEASE MORE. 1642 00:56:29,320 --> 00:56:33,440 BUT WITHOUT ANY FURTHER 1643 00:56:33,440 --> 00:56:34,800 QUESTIONS, IF YOU ANY ANY 1644 00:56:34,800 --> 00:56:35,840 CLOSING REMARKS WE WOULD LOVE TO 1645 00:56:35,840 --> 00:56:36,320 HEAR FROM YOU. 1646 00:56:36,320 --> 00:56:38,200 >>I WANT TO THANK YOU SO MUCH 1647 00:56:38,200 --> 00:56:39,520 FOR THE INVITATION AND I KNOW 1648 00:56:39,520 --> 00:56:40,720 THIS IS RECORDED SO PEOPLE CAN 1649 00:56:40,720 --> 00:56:42,680 WATCH IT LATER AND I HOPE TO 1650 00:56:42,680 --> 00:56:44,640 INSPIRE PEOPLE TO INNOVATE AND 1651 00:56:44,640 --> 00:56:45,840 QUESTION WHEN SOMEONE TELLS YOU 1652 00:56:45,840 --> 00:56:47,280 THERE'S NOTHING THAT CAN BE DONE 1653 00:56:47,280 --> 00:56:48,320 OR THE STABBED ARD OF CARE, THIS 1654 00:56:48,320 --> 00:56:50,760 IS THE BEST IT GETS, THINK ABOUT 1655 00:56:50,760 --> 00:56:53,160 IT, ASK ABOUT IT, THINK 1656 00:56:53,160 --> 00:56:53,760 CAREFULLY AND SCIENTIFICALLY 1657 00:56:53,760 --> 00:56:55,680 ABOUT SO THAT WE CAN CHANGE HOW 1658 00:56:55,680 --> 00:56:56,520 MEDICINE IS PRACTICED. 1659 00:56:56,520 --> 00:57:00,000 SO THANK YOU ALL FOR YOUR 1660 00:57:00,000 --> 00:57:01,160 ATTENTION. 1661 00:57:01,160 --> 00:57:01,720 >>THANK YOU DR. DIXON. 1662 00:57:01,720 --> 00:57:03,760 >>AND THANK YOU DR. TEKE, FOR 1663 00:57:03,760 --> 00:57:05,360 THE INTRODUCTION AND MODERATING, 1664 00:57:05,360 --> 00:57:06,680 I APPRECIATE IT AND EVERYONE 1665 00:57:06,680 --> 00:57:07,240 HAVE A WONDERFUL DAY. 1666 00:57:07,240 --> 00:57:08,000 >>PLEASURE. 1667 00:57:08,000 --> 00:57:36,720 THANK YOU.