The outline of the programme is as follows:
27 April 2011 Wednesday at 17:30 -19:00
- Opening remarks
- Sven Erik Hansen (On the origin of institutions for medical education and treatment in 18th century Copenhagen) 15 mins
- Ole H Nielsen (History of Paediatric Urology in Denmark) 15 mins
- Michael Ritchey (Introduction of chemotherapy for Wilms tumor, with a focus on Dr Dana Farber) 15 mins
- Faruk Hadziselimovich (History of undescended testis) 15 mins
- John Hutson (The history of Paediatric Urology: Australia’s first paediatric urologist) 15 mins
- Concluding Remarks
On the origin of institutions for medical education and treatment in 18th century Copenhagen.
Sven Erik Hansen
In the 18th century The Danish state comprised Denmark, Norway, Schleswig and Holstein with a long coast line from the river Elbe to the Arctic Ocean. Copenhagen was the capital, and base for a big navy which ran a hospital for sailors. In 1736 a school of surgery was established for the improvement of the education of barber surgeons. In the mid-18th century Danish trade prospered, and the city of Copenhagen became enlarged by a new district called “Frederiksstaden” after the king Frederic V. The best architects created a range of magnificent buildings, several of which were intended for medical purposes. In 1757 a big hospital opened for clinical education of physicians and both military and civil surgeons. The buildings still exist as a museum for decorative arts. In addition a maternity ward, a nursing home for abandoned infants, a municipal hospital and a botanical garden were established close to each other. Finally in 1787 the school of surgery was accommodated in a new spacious Academy of Surgery, the present day’s Medical Museion. The buildings and the activities in them, the first medical center of Copenhagen, will be described
History of Pædiatric Urology in Denmark
Ole H Nielsen
Records of pædiatric urology in Denmark before 1950 are sporadic. Undescended testes and hypospadias are treated randomly in surgical departments. There is no tradition of circumcision in Denmark. The few childrens’ hospitals - later to be closed – had no surgical departments, and there are no records of treatment of congenital anomalies.
In 1950 a pædiatric surgical service was established within the pædiatric department of Copenhagen University Hospital with C.C. Winkel Smith as chief. All branches of soft tissue pædiatric surgery are taken up, and for the first time the term Pædiatric Urology is used. In the 1960’s there is a debate in the medical press about the treatment of undescended testes, because endocrinologists maintain that surgery is harmful and causes infertility. In the 1970’s pædiatric urologic activity starts in the urological department of Aarhus University Hospital and it develops in the following years.
In Copenhagen urodynamics was taken up in the 1960’s and under Ole Henrik Nielsen and Jørgen Thorup the department has contributed to pædiatric urology in the fields of hydronephrosis, undescended testes, prænatal diagnosis, neuroblastoma, neurogenic bladder and urogenital and intersex conditions.
In Aarhus, under Troels Munch Jørgensen and Henning Olsen activities have centered mainly on hydronephrosis and vesico-ureteral reflux, and on laparoscopic robotic surgery.
Evolution of chemotherapy treatment for Wilms tumor
Chemotherapy was introduced for the treatment of pediatric solid tumors just over five decades ago. Prior to that time, surgery and radiotherapy were the only effective treatment modalities. Actinomycin D was the first agent shown to be effective for treatment of Wilms tumor. Actinomycin, derived from Streptomyces and discovered in 1940, was initially thought to be useful as an antibiotic. The drug was noted to be too toxic causing myelosuppression.
Actinomycin D was noted to have anticancer activity in animal models by Dr. Sidney Farber, a pathologist at Harvard. Farber had previously reported the successful treatment of acute leukemia in children with antifolate drugs. They noted that actinomycin D could eliminate some metastases in children with advanced Wilms tumor. More importantly, they demonstrated improved survival in children when the drug was given immediately after nephrectomy. This was the beginning of routine adjuvant therapy for the treatment of solid neoplasms in children. Dr. Dan D’Angio, a radiation oncologist and one of the founders of the National Wilms Tumor Study, working with Dr. Farber reported that the effects of radiotherapy could be potentiated by administration of actinomycin D.
Vincristine, a plant alkaloid derived from the periwinkle plant, was the second drug shown to marked activity in children with Wilms tumor. Dr. Wataru Sutow, an oncologist at M. D. Anderson Cancer Center, showed that this drug could rapidly reduce the size of metastases and the primary tumor with little myelosuppression. These two drugs, dactinomycin and vincristine, were later studied as a combination therapy in the first randomized trial for the treatment of Wilms tumor conducted by the National Wilms Tumor Study.
Infertility and Cryptorchidism – A Historical Perspective
In 1786, John Hunter attributed the cause of congenital malformation of one of both testes to infertility development. During last three centuries, different hypotheses were put forth as possible causes of infertility in cryptorchid males. They included: 1) congenital malformation, 2) secondary damage to initially normal testis due to persistent malposition, or 3) endocrinopathy leading to defective spermatogenesis.Research into infertility caused by cryptorchidism was greatly influenced by studies of testicular histology. The first histological description of pre-pubertal undescended testes was published by Felizet and Branca in 1898. In 1940, Charny reported the feasibility of performed sequential biopsies of cryptorchid testis in boys who had successful orchidopexy. He realized that in those boys with severe pathological changes in their undescended testes at the time of the surgery, no improvement of testicular tissue was seen for several years/months after the successful orchidopexy. Therefore, he postulated that cryptorchid testis must be a congenital malformation. Performing the surgery early in life, from age 2 years up to shortly before puberty was recommended in the early 70es, but this had already been propagated by Eisendrath in 1916 and was later supported by histological examination Southam and Cooper in 1927. However in 1965, Hedinger was able to show, using an improved histological technique, that testis of cryptorchid boys younger than 2 years of age had normal numbers of germ cells. Therefore, it was postulated that orchidopexy of cryptorchid boys had to be performed before the second birthday. During the last 70 years, substantial evidence has appeared in the literature to support a strong correlation between unilateral or bilateral testicular malposition and the incidence of azoospermia. This mean incidence for bilateral malposition is 23% and, for unilateral, 10% , regardless of the age at the time of surgery. Thus early and successful surgery could not prevent the development of azoospermia. In 1977, the Nobel Prize was awarded to eminent peptide chemists for their pioneering work on neuropeptides including GnRH. Soon after GnRH synthesis was realized, Job et al found LH deficiciency in unilateral cryptorchid boys and were later the first to describe a blunted T increase during physiological T surge in infancy. The importance of T surge become clear, only recently when the results of histological analyses of the biopsies taken at the surgery were compared with the fertility results. It became clear that mini-puberty is not an insignificant physiological gonadotropin rebound phenomenon, but rather the critical point for determination of future male fertility. Recently, advances in molecular genetics of cryptorchidism have provided necessary evidence to disprove Hunters more than 220 year old thesis that cryptorchid testis is a congenital abnormality that is ab initio imperfect and incapable of development into normal testicular structure and function.
The history of Paediatric Urology: Australia’s first paediatric urologist
John M. Hutson
The history of paediatric urology is the history of Douglas Stephens (FDS). Born 1913, son of Henry Douglas Stephens, a paediatrician and surgeon at Royal Children’s Hospital Melbourne for 50 years. Joined the army medical corps after early surgical training. Served in Tobruk. Returned to Melbourne 1945, scholarship to GOS in 1947-1950 (where he worked with Sir Denis Browne). Began studying anorectal anatomy and embryology. Returned to RCH in 1950 and established Urology Unit. Studied urinary tract anomalies 1950-1963. First book 1963 on malformations. “Anorectal Malformations in Children” in 1971, with Durham Smith. “Discovered” by American urologists and moves to Children’s Memorial Hospital, Chicago, for 12 years. “Congenital Anomalies of the kidney, urinary and genital tracts” published in 1996, with the second edition in 2002 when FDS is 89.