UNKNOWN TO ME ON ONE OCCASION, THE MEMBER OF THE

PEDIATRIC STAFF WHO HAD REFERRED A WILMS' TUMOR TO ME,

TOOK FOUR MEDICAL STUDENTS ON ROUNDS TO FEEL THE MASS

WHILE I WAS OPERATING ON THE PRECEDING CASE. WHEN I

OPENED THE ABDOMEN, THE WILMS' TUMOR WAS RUPTURED AND

FRIABLE MALIGNANT TISSUE WAS FOUND THROUGH THE

RETROPERITONEUM; THE HEMORRHAGE HAD EXTENDED WELL TO

THE CONTRALATERAL SIDE AND HAD MADE ITS WAY UP INTO THE

MESOCOLON OF THE ASCENDING AND TRANSVERSE BOWELS.


THAT PATIENT DIED.

51


ONE OF THE MOST HORRENDOUS SURGICAL PROCEDURES IN

REFERENCE TO A WILMS' TUMOR THAT WE EVER UNDERTOOK

WAS A NEPHRECTOMY IN CONJUNCTION WITH THE REMOVAL, VIA

THE RENAL VEIN, OF A TUMOR THROMBOUS THAT EXTENDED UP

THE VENA CAVA, TURNED THE CORNER, AND ENDED IN THE RIGHT

ATRIUM. POSTOPERATIVELY, IN ORDER TO DEMONSTRATE, FOR

TEACHING PURPOSES, WHAT WE HAD DONE, AND WHILE THE

CHILD WAS STILL ON THE OPERATING TABLE IN A SUPINE

POSITION, WE PLACED THE TUMOR NEXT TO HIM AT HIS RIGHT

FLANK AND THEN LAID THE THROMBUS ON HIS BODY TO MIMICK

ITS INTERNAL POSITION.

52


IT STARTED AT THE LEVEL OF HIS LIGATED RENAL VEIN AND LAY

ACROSS HIS RIBCAGE AND TURNED AROUND TO END IN A
   @

BULBUS MASS JUST OVER HIS RIGHT ATRIUM.

WHEN, A YEAR OR SO LATER, I WAS PRESENTING A PAPER AT THE


BOSTON CITY HOSPITAL AS PART OF A SYMPOSIUM ON CANCER

IN CHILDHOOD, I SHOWED THIS CASE, INCLUDING A


MICROSCOPIC SECTION OF THE TIP OF THE THROMBUS FOUND IN

THE ATRIUM.

53


THERE WAS NO DOUBT THE THROMBUS WAS WILMS' TUMOR AND

THAT WAS THE ONLY POINT I WAS TRYING TO MAKE. IN THE

AUDIENCE, HOWEVER, WAS JUDAH FOLKMAN, THEN SURGEON-

IN-CHIEF OF THE CHILDREN'S HOSPITAL OF BOSTON, AND A

SCIENTIST WITH A LIFE-LONG INTEREST IN THE ANGIOGENESIS

FACTOR. AMONG OTHER CONCERNS, HIS THESIS WAS THAT

TUMORS CANT GROW WITHOUT BLOOD SUPPLY. WHERE DO THE

BLOOD VESSELS COME FROM, AND WHAT TRIGGERS THEIR

DEVELOPMENT?

54


I PUSHED A BUTTON ON THE PODIUM TO MOVE THE SLIDE AND

DR. FtkKMAN CRIED OUT, "WAIT, WAIT!" I BACKED THE SLIDE UP.

THERE HE DEMONSTRATED SOMETHING I HAD NOT SEEN. ON THE

VERY TIP OF THE THROMBUS, IN THE MIDST OF THE TELLTAIL

HISTOLOGY OF WILMS' TUMOR, THERE WERE TINY BLOOD

VESSELS GROWING MORE THAN TWO FEET AWAY FROM THE

PRIMARY TUMOR THAT GAVE BIRTH TO THE THROMBUS.

55


IT WAS, OF COURSE, THE ADVENT OF CHEMOTHERAPY THAT


CHANGED THE WHOLE CONCEPT OF THE MANAGEMENT OF

CHILDHOOD CANCER,--AND IT AFFECTED WILMS' TUMOR FIRST.

IT IS INTERESTING THAT UP UNTIL THE ADVENT OF

CHEMOTHERAPY, ALL OF THE MAJOR CHILDRENS HOSPITALS IN


THE COUNTRY HAD ABOUT THE SAME SURVIVAL RATE FOR

WILMS' TUMOR USING JUST ABOUT THE SAME PROTOCOL THAT I

HAVE DESCRIBED. SEVERAL OF US HAD ACHIEVED 47 POINT

SOMETHING % SURVIVAL BEFORE CHEMOTHERAPY. I KNOW OF

NO ONE WITH A RESPECTABLE SERIES WHO REACHED 48%.

56


UNTIL CANCER CHEMOTHERAPY GAINED A FOOTHOLD, THE

MANAGEMENT OF CHILDHOOD CANCER WAS THE SURGEON'S

DOMAIN, WITH AN ASSIST FROM THE RADIOLOGIST.

COLLEAGUES IN INSTITUTIONS SIMILAR TO MY OWN WERE NOT

ONLY SURGEONS AND PEDIATRICIANS, BUT FAMILY COUNSELORS

AND CHAPLAINS AS WELL. WITH THE ADVENT OF

CHEMOTHERAPY, THE SPECIALTY OF PEDIATRIC ONCOLOGY

CAME INTO ITS OWN. THERE IS NO DOUBT THAT BECAUSE OF

AVAILABLE RESEARCH FUNDING, THE INTEREST IN A NEW

FRONTIER, AND THE INCREASING SUCCESS WITH CHEMOTHERAPY

FOR WILMS' TUMOR AND RHABDOMYOSARCOMA (AS WELL AS

GREAT SUCCESS IN THE MANAGEMENT OF LEUKEMIA),

ONCOLOGY BEGAN TO ATTRACT MORE AND MORE BRIGHT YOUNG


PEDIATRICIANS AND HEMATOLOGISTS.

57


I HAVE CONSIDERABLE PRAISE FOR MEDICAL ONCOLOGISTS AND

THEIR ACCOMPLISHMENTS. I THINK, IN MANY INSTITUTIONS

ACROSS THE LAND, WHAT COULD HAVE BEEN A MAJOR THRUST

BY MANY DISCIPLINES INVOLVED IN THE MANAGEMENT OF THE

JUVENILE CANCER PATIENT FELL SHORT OF THE MARK. AS THE

ONCOLOGIST HAS RISEN, SO HAS THE PERCEPTION OF THE

VALUE OF THE SURGEON FALLEN. IT WOULD BE TRAGIC, IF, WITH

THE HISTORY OF THE PAST FEW YEARS, THE SURGEON IS

RELEGATED TO THE POSITION OF TECHNICIAN TO THE MEDICAL

ONCOLOGIST.

58


IT IS IRONIC THAT MOST GOOD MEDICAL ONCOLOGISTS WERE


ATTRACTED TO THEIR PRESENT SUB-SPECIALTY BY THE


REPUTATION AND CASE LOAD OF A PEDIATRIC SURGICAL

CANCER ENTHUSIAST.

AS FASCINATING AS ALL CHILDHOOD MALIGNANT TUMORS WERE,


IT WAS THE NEUROBLASTOMA AND ITS PECULIAR LIFE HISTORY

THAT RIVETED MY ATTENTION,--EVEN EARLY ON.

59


WHEN I DID MY RETROSPECTIVE STUDY OF RECORDS OF

DISCHARGE DIAGNOSES WITH MALIGNANT TUMORS, I HAD BEEN

N STRUCK THAT 25% OF THEM WERE NEUROBLASTOMA. I

ATTEMPTED TO TRACE THESE CHILDREN, FOUND THAT MOST OF

THEM HAD DIED, BUT THAT SOME RATHER REMARKABLE


YOUNGSTERS HAD SURVIVED.

ONE HAD BEEN IN THE HANDS OF A NEUROSURGEON WHO HAD

DONE A LAMINEt=TOMY AND REMOVED A PORTION OF A HIGHLY

UNDIFFERENTIATED NEUROBLASTOMA, CLOSING THE PATIENT UP

TO DIE.

60


IN RETROSPECT I THINK EVERYBODY MISSED THE ABDOMINAL

TUMOR, OF WHICH THE INT-RASPINAL EXTENSION WAS THE SMALL

END OF A DUMBBELL. SOME YEARS LATER WHEN SOMEBODY

FELT AN ABDOMINAL TUMOR IN THIS NOW PARAPLEGIC CHILD, IT

WAS BIOPSIED AND PROVED TO BE A QUITE BENIGN

GANGLIONEUROMA. THE OTHER LIVING PATIENTS IN THAT SMALL

GROUP OF NEUROBLASTOMA SURVIVORS IMPRESSED ME THAT

THE THERAPY SEEMED TO HAVE HAD LITTLE OR NOTHING TO DO

WITH SURVIVAL.

61


OF COURSE I CAN ONLY SPEAK ABOUT THOSE CHILDREN AND

KNEW NOTHING ABOUT THE QUALITY OR QUANTITY OF

TREATMENT ON THOSE WHO DIED.

EARLY IN MY TENURE AT CHILDRENS HOSPITAL, I WAS CALLED

UPON TO TREAT AN ABDOMINAL MASS IN THE INFANT SON OF A

FORMER RESIDENT WHO HAD MARRIED ONE OF OUR NURSES.

DURING SURGERY, I RUPTURED THE PSEUDOCAPSULE OF A

PERIRENAL NEUROBLASTOMA.

62


IN ADDITION TO THAT POOR PROGNOSTIC SIGN, THE CHILD ALSO

HAD MULTIPLE BARELY VISIBLE METASTASES TO THE LIVER,


CONFIRMED BY BIOPSY. THE SURGERY WAS CERTAINLY NOT THE


METICULOUS SURGERY OF CANCER THAT I HAD BEEN TAUGHT.


THERE WAS GROSS SPILL OF TUMOR THROUGHOUT THE


PERITONEAL CAVITY. I TOLD THE FAMILY THE SITUATION WAS


HOPELESS AND NO RADIATION THERAPY SHOULD BE GIVEN.

SIX WEEKS LATER THE CHILD RETURNED FOR A POSTOPERATIVE

VISIT AND HAD MULTIPLE SUBCUTANEOUS NODULES WHICH I


ASSUMED TO BE TUMOR. I DID NOT ASK FOR A BIOPSY.

63


THE YOUNGSTER WAS SENT HOME TO DIE. THAT PATIENT


EVENTUALLY GRADUATED FROM LAW SCHOOL AND WHEN LAST

SEEN BY ME, THE PYELOGRAM SHOWED NOTHING MORE THAN A

DISTORTED CAL& OF ONE KIDNEY ON THE SIDE OF THE               i/


SURGERY.

64


A THREE AND ONE-HALF YEAR OLD GIRL WAS SENT TO ME WITH

THE DIAGNOSIS OF SPLENOMEGALY. IT WAS OBVIOUS THAT THE

MASS IN QUESTION WAS NOT A SPLEEN, BUT A TUMOR, AND

AFTER SUITABLE WORKUP, ABDOMINAL EXPLORATION REVEALED

A MALIGNANT NEUROBLASTOMA ARISING FROM THE ABDOMINAL

SYMPATHETIC CHAIN, FASTENED TIGHTLY TO THE SPINAL

COLUMN AND DIFFUSE ENOUGH IN THE RETROPERITONEUM AS

TO BE NONRESECTABLE.

THE TUMOR WAS SOFT AND SUCCULENT, AND AFTER OPENING

THE POSTERIOR P ERITONEUM, IN THE COURSE OF BIOPSY,

THERE WAS GROSS SPILL OF THE TUMOR INTO THE PERITONEAL

CAVITY.

65


I PRESENTED THE FATHER WITH A HOPELESS PROGNOSIS AFTER

WHICH HE BEGAN TO READ BROADLY ABOUT NEUROBLASTOMA,-

-WHAT LITTLE THERE WAS WRITTEN ABOUT IT,--AND BECAME AN

ALLY WITH ME AGAINST THE TUMOR.

THE TUMOR SLOWLY ENLARGED AND ITS LOWER TIP, WHICH HAD

BEEN PALPABLE JUST BELOW THE COSTAL CAGE, DESCENDED

UNTIL IT REACHED THE PELVIS, TURNED TOWARD THE RIGHT,

AND EVENTUALLY POINTED UPWARD IN THE RIGHT LOWER

QUADRANT. AFTER A PERIOD OF STABILIZATION THERE, THE

TUMOR SLOWLY RECEDED IN THE DIRECTION FROM WHENCE IT

HAD COME UNTIL IT WAS BARELY PALPABLE HIGH UP UNDER THE

COSTAL CAGE ON THE LEFT. BY THAT TIME, IT WAS THE FATHER,

NOT I, WHO WAS PUSHING FOR ANOTHER LOOK.

66


THIS WE DID AND FOUND AN EXTREMELY FIRM, SMALL

GANGLIONEUROMA ABOUT THE SIZE OF A TENNIS BALL, WHICH I

RESECTED, WITHOUT BEING ABLE TO DETACH EVERY CELL FROM

THE SPINAL COLUMN. THE CHILD SURVIVED, AND WAS LOST TO


FOLLOW-UP IN HER TEENS.

THE SURVIVAL OF THOSE YOUNGSTERS FOLLOWING GROSS

SPILL OF THE TUMOR INTRAPERITONEALLY LED ME TO BELIEVE


THAT PERHAPS THE VERY SPILL MIGHT HAVE HAD A BENEFICIAL

EFFECT. AFTER MORE EXPERIENCE, MY FIRST PRESENTATION ON


THE SUBJECT OF NEUROBLASTOMA WAS BEFORE THE SOCIETY

OF UNIVERSITY SURGEONS IN 1955.

67


I ENTITLED THE PAPER "NEUROBLASTOMA IN CHILDHOOD: THE

EFFECT OF MAJOR SURGICAL INSULT ON SURVIVAL." I

REPORTED A 38% SURVIVAL IN MY EXPERIENCE THUSFAR.

IN A DISCUSSION FOLLOWING MY PRESENTATION, CRITICS

SUGGESTED THAT IF ONLY I HAD BEEN SMART ENOUGH TO USE

RADIATION THERAPY IN ADDITION TO SURGERY, I COULD HAVE

IMPROVED MY RESULTS.

68


THE NEXT EIGHT NEUROBLASTOMAS I TREATED WITH RADIATION.

ALL OF THEM DIED. I THEN RETURNED TO MY LONG-HELD BELIEF

TtiAT THE ADJUNCT OF RADIATION THERAPY FOR

NEUROBLASTOMA DID NOT REALLY INCREASE SURVIVAL.

THIS POSITION, WHICH WAS LATER CLARIFIED BY THE WORK OF

MANY OTHERS, EVENTUALLY LED TO OUR UNDERSTANDING OF

THE CURRENT STAGING OF NEUROBLASTOMA. SOME

YOUNGSTERS, FOR EVERY SCIENTIFIC REASON, ENTITLED TO A

POOR PROGNOSIS AND m ON THEIR WAY TO DEATH, WERE

PATIENTS WITH STAGE IV-S DISEASE.


THEIR PROGNOSIS WAS NOT IMPROVED BY RADIATION AND

THEIR SURVIVAL WAS ALMOST UNIFORMLY GOOD.

WHEN I LEFT THE PRACTICE OF SURGERY IN 1981 TO GO TO

WASHINGTON, MY OWN SURVIVAL RATE WAS THE SAME 38% THAT

MY PATIENTS ENJOYED IN 1955, IN SPITE OF ADJUNCTIVE

RADIATION AND CHEMOTHERAPY. UNFORTUNATELY,

NEUROBLASTOMA HAS NEVER HAD THE REMARKABLE

SUCCESSFUL INCREASE IN SURVIVAL THAT WAS ACCOMPLISHED

FOR WILMS' TUMOR WITH CHEMOTHERAPY.

70


I GUESS THE FIRST OF MANY SURGICAL AND PUBLIC HEALTH


CRUSADES OF MY LIFE CENTERED AROUND AWAKENING


PEDIATRICIANS TO THE POSSIBILITY OF DIAGNOSING CANCER IN

CHILDREN. ITS HARD TO BELIEVE, @I!`@59 AT THIS LATE TIME,

HOW DIFFICULT IT WAS TO FIND RECEPTIVE AUDIENCES AMONG


PEDIATRICIANS. AS I TRIED TO AROUSE A FEELING OF GUILT FOR

MISSING DIAGNOSES, BUT AT THE SAME TIME PROVIDING A WAY

OUT FOR THE IMPOSSIBLE PROBLEMS, I USED TO SPEAK OF


FOUR CATEGORIES OF TUMOR:

71


1.   THE VISIBLE OR PALPABLE LESION WHICH NO ONE COULD

  BE EXCUSED FOR MISSING;

2.  THE TUMOR THAT, BY ITS SYMPTOMATOLOGY, SHOULD

   AROUSE SUSPICION OF CANCER IF ONE INCLUDED IT IN THE

  DIAGNOSTIC POSSIBILITIES;

3.   THOSE TUMORS WHOSE SYMPTOMS MIMICKED OTHER

  MORE FAVORABLE DIAGNOSES (SUCH AS THE DIAGNOSIS OF

RHEUMATIC FEVER, INSTEAD OF NEUROBLASTOMA);

4.   THE TUMORS HERALDED BY SUCH VAGUE

  SYMPTQMATOLOGY THAT NO ONE COULD BE BLAMED FOR A


   DELAYED DIAGNOSIS.

72


AS I LOOK BACK OVER THE LAST HALF-CENTURY, IT'S HARD TO


BELIEVE HOW LITTLE WE ALL KNEW WHEN I GRADUATED FROM


MEDICAL SCHOOL AND WHAT TREMENDOUS ADVANCES THERE


HAVE BEEN IN MEDICINE DURING MY LIFETIME.

73


THE OPPORTUNITIES FOR LABORATORY AND CLINICAL

INVESTIGATIONS OF CHILDHOOD CANCER ARE STILL LEGION. I

STILL FEEL THAT IF SOMEONE COULD UNDERSTAND, IN ITS

TOTALITY, THE BEHAVIOR OF NEUROBLASTOMAS, A KEY WOULD

TURN IN MANY LOCKS IN OUR UNDERSTANDING OF

ONCOGENESIS, MATURATION, AND SPONTANEOUS REMISSION.

OF COURSE, ADJUNCTS TO THERAPY WOULD SOON FOLLOW. I

THINK THAT COMBINATIONS OF ADJUNCTIVE THERAPY ALONG

WITH SURGERY WILL CONTINUE TO LOWER MORTALITY RATES

BUT ONLY SLOWLY WHILE I'NCREASING THE LONGEVITY OF

CHILDREN DESPITE THE ULTIMATE FATAL OUTCOME. THE REAL

BREAKTHROUGH, I THINK, WILL COME WITH A BETTER

UNDERSTANDING OF THE IMMUNOLOGY OF CANCER AS WELL AS

THE ELUCIDATION OF THE COMBINED FACTORS OF GENETIC

PROPENSITY AND ENVIRONMENTAL STIMULI.

74


WHILE THE DAY-TO-DAY CARE OF THE YOUNGSTER WITH THE


MALIGNANT TUMOR IS ONE OF THE ULTIMATE CHALLENGES IN

PEDIATRIC MANAGEMENT, THE IMPROVED SURVIVAL OF PATIENTS


WITH PEDIATRIC MALIGNANT TUMORS HAS BEEN ONE OF THE


OUTSTANDING SUCCESSES IN THE FIELD OF ONCOLOGY. IT HAS


BEEN A GOOD TIME TO BE ALIVE.

--END--

75