Pediatric Annals

A Pediatrician's View

Milton I Levine, MD

Abstract

Back in the early 1920s, my pre-medical days, I was a student of an inspiring and very famous biology professor. He was close to all of his students and frequently, on a Saturday or Sunday, would take us on walks into the countryside where we could observe animal life closely - in and on the ground, in lakes and streams, in bushes and trees, and in the air. Those were exciting, stimulating, happy and memorable days.

Frequently, the professor's daughter, a lovely little six or seven year old girl, would come on these hikes with us. She always wore a hat or bandanna to cover her head, for she was completely bald. Her father told us she had "ringworm of the scalp" and had received x-ray treatment - the standard treatment at that time. Her hair had fallen out and had never grown back.

Five years later this child developed a brain tumor and died within a few months. We felt, even in those early days, that there was a relationship between the scalp treatment and the malignancy.

However, this method of therapy continued for many years. According to a 1940 textbook, "Cure is difficult without epilation . . . Temporary roentgen epilation of the whole scalp, even if one or two small areas be involved, is the best preliminary measure to a cure in this usually obstinate and troublesome malady." Even into the 1960s, x-ray treatment was still advised for resistant cases. Griseofulvin was not yet discovered. We know today that our fears were probably well-grounded.

There was a time when if an infant had a laryngeal stridor, and x-ray revealed an enlarged thymic shadow, the routine treatment was radiation therapy which rapidly reduced the size of the thymus. This was in the late 1920s and into and through the 1930s. Some years later many of these children developed cancer of the thyroid gland.

We still know too little about the origin of cancer. We formerly believed that osteosarcoma was caused by an injury. It was found most frequently in adolescent boys, many of whom had been involved in sports. But studies have proven that trauma is not the etiological factor. In certain cases of cancer heredity seems to be a contributing cause, in other cases x-ray therapy or environmental conditions such as toxic waste or nuclear radiation appear to be involved.

However, within this past year there has been intense excitement in the field of oncogenesis as a result of genetic studies at the molecular level. This excitement has focused on the identification of certain genes called oncogenes which are thought to be responsible for causing cancer. Apparently, the oncogenes regulate the amount of protein in cells and are quiescent or they are under strict control by a cell. But, under certain influences, the cell loses control and the oncogenes are activated to cause unwanted protein growth, initiating cancer. If these theories are correct it may indicate that the oncogenes may be activated by any of the conditions known to be oncogenic such as irradiation, nuclear contact, or environmental toxic hazards in water, food or air.

It is much too early to determine if these new scientific advances will lead to the prevention or even treatment of cancer. But Dr. Lewis Thomas of the Memorial Sloan-Kettering Cancer Center in New York City is quoted in The New York Times as stating that he expects "the end of cancer before the century is over."

The second issue of the three-part symposium on cancer in infancy and childhood is once again under the guest editorship of Dr. Carl Pochedly.

This…

Back in the early 1920s, my pre-medical days, I was a student of an inspiring and very famous biology professor. He was close to all of his students and frequently, on a Saturday or Sunday, would take us on walks into the countryside where we could observe animal life closely - in and on the ground, in lakes and streams, in bushes and trees, and in the air. Those were exciting, stimulating, happy and memorable days.

Frequently, the professor's daughter, a lovely little six or seven year old girl, would come on these hikes with us. She always wore a hat or bandanna to cover her head, for she was completely bald. Her father told us she had "ringworm of the scalp" and had received x-ray treatment - the standard treatment at that time. Her hair had fallen out and had never grown back.

Five years later this child developed a brain tumor and died within a few months. We felt, even in those early days, that there was a relationship between the scalp treatment and the malignancy.

However, this method of therapy continued for many years. According to a 1940 textbook, "Cure is difficult without epilation . . . Temporary roentgen epilation of the whole scalp, even if one or two small areas be involved, is the best preliminary measure to a cure in this usually obstinate and troublesome malady." Even into the 1960s, x-ray treatment was still advised for resistant cases. Griseofulvin was not yet discovered. We know today that our fears were probably well-grounded.

There was a time when if an infant had a laryngeal stridor, and x-ray revealed an enlarged thymic shadow, the routine treatment was radiation therapy which rapidly reduced the size of the thymus. This was in the late 1920s and into and through the 1930s. Some years later many of these children developed cancer of the thyroid gland.

We still know too little about the origin of cancer. We formerly believed that osteosarcoma was caused by an injury. It was found most frequently in adolescent boys, many of whom had been involved in sports. But studies have proven that trauma is not the etiological factor. In certain cases of cancer heredity seems to be a contributing cause, in other cases x-ray therapy or environmental conditions such as toxic waste or nuclear radiation appear to be involved.

However, within this past year there has been intense excitement in the field of oncogenesis as a result of genetic studies at the molecular level. This excitement has focused on the identification of certain genes called oncogenes which are thought to be responsible for causing cancer. Apparently, the oncogenes regulate the amount of protein in cells and are quiescent or they are under strict control by a cell. But, under certain influences, the cell loses control and the oncogenes are activated to cause unwanted protein growth, initiating cancer. If these theories are correct it may indicate that the oncogenes may be activated by any of the conditions known to be oncogenic such as irradiation, nuclear contact, or environmental toxic hazards in water, food or air.

It is much too early to determine if these new scientific advances will lead to the prevention or even treatment of cancer. But Dr. Lewis Thomas of the Memorial Sloan-Kettering Cancer Center in New York City is quoted in The New York Times as stating that he expects "the end of cancer before the century is over."

The second issue of the three-part symposium on cancer in infancy and childhood is once again under the guest editorship of Dr. Carl Pochedly.

This present segment of the symposium is devoted to malignant tumors and will discuss those most common during childhood and adolescence. These are Wilms' tumors, neuroblastomas, osteosarcomas, brain tumors, and rhabdomyosarcomas.

Those of us who have practiced pediatrics for a number of years have had the upsetting experience of occasionally diagnosing malignancies in our patients. At times we can make the diagnosis by simple x-ray. In other cases the diagnosis becomes most difficult.

I often reflect on these "mystery cases" and wonder if 1 would make a quicker diagnosis if I saw them today.

Some years ago, I completely missed the diagnosis on a seven-year-old girl who had what at first seemed to be an upper respiratory infection. But the next day her mother called to tell me that the child was complaining of abdominal pain and that her skin had a yellowish tint. I went to my patient's home and on examining her found her to be mildly jaundiced with a slightly enlarged and slightly tender liver. A blood count and urinalysis were normal but there was, as expected, a rise in serum bilirubin and a darkening in color of the urine. Liver function tests were reported as normal.

I told the mother that, in my opinion, her daughter had infectious hepatitis, that the prognosis was excellent in children, that the jaundice should leave in a few weeks and that her child should be normal again.

But the jaundice did not clear and the abdominal pain, rather than lessening became more severe. Finally, we hospitalized the child and an abdominal operation disclosed a rhabdomyosarcoma of the liver.

In most cases the signs and symptoms lead us to the diagnosis whether it be a palpable abdominal tumor, a painful leg, or the frequent headaches and vomiting that direct us to the possibility of a brain tumor.

It should be remembered, however, that many malignancies originate with few or no symptoms. Fortunately, malignancies are comparatively rare in children, but the fact that the earlier the diagnosis is made the better the chance is for a cure, makes it essential that every child be examined most carefully at each annual visit.

The first article in this symposium, on "Wilms' Tumors" has been written by Dr. Edward S. Baum and Dr. Elaine R. Morgan, both Assistant Professors at Northwestern University Medical School and members of the Division of Hematology/ Oncology at Children's Memorial Hospital, Chicago, Illinois.

This is one of the most common malignant tumors in infancy and early childhood. It follows brain tumors in frequency and usually occurs during the first three years of life. It is usually diagnosed by the parents noting the enlarged abdomen of the child, or the pediatrician finding an abdominal mass on examination.

Until less than 15 years ago our routine treatment of rapid surgical removal plus irradiation was successful in less than 10% of the cases.

Dr. Baum and Dr. Morgan review the present status of therapy enhanced by the use of chemotherapy. Under this modern approach the cure rate for children with Wilms' tumor has risen to more than 80%.

The second paper deals with "Neuroblastomas" and is contributed by Dr. F. Ann Hayes and Dr. Alexander A. Green, both Associate Professors of Pediatrics at the University of Tennessee and Associate Members of the Division of Hematology/ Oncology at St. Jude Children's Research Hospital, Memphis, Tennessee.

Neuroblastomas are the most common solid malignant tumors of young children, with the vast majority of cases being diagnosed in the first five years of life. There is rapid metastasis making it especially urgent for the examining pediatrician to diagnose the condition as early as possible. The authors of this paper emphasize the importance of a good abdominal examination, for a neuroblastoma tumor often enlarges in the abdomen or pelvic region without any other signs or symptoms.

This article carefully reviews the clinical manifestations and diagnostic approach for neuroblastomas. The authors then point out that prognosis depends on the extent of the disease at diagnosis. Various means of therapy are presented: surgery, radiation, and chemotherapy, with chemotherapy being the most valuable.

Of course, therapy should be in the hands of an oncologist. Nevertheless, the pediatrician is of vital importance, for this is where the responsibility rests for early diagnoses, a prerequisite for remissions or an eventual cure.

The next contribution is on "Osteosarcoma" and has been written by Dr. Lawrence J. Ettinger of the Division of Hematology/ Oncology of the Children's Hospital of Los Angeles, and Assistant Professor of Pediatrics at the UCLA School of Medicine.

Dr. Ettinger notes at the outset that prior to the approximate date of 1970 the diagnosis of osteosarcoma was essentially a death warrant, even though amputation was used in almost all cases. Today, he reports, "50% or more of all children and adolescents with newly diagnosed osteosarcomas will be long-term survivors and potentially will be cured of their malignancy."

This improved survival rate is, of course, due to chemotherapy. Prior to its use, more than 80% of patients who underwent amputation for the condition subsequently developed pulmonary metastases.

An interesting new approach to treatment of osteosarcoma is reported in a study by Rosen et al at the Memorial Sloan-Kettering Cancer Center of New York. Here chemotherapy is given for four to 16 weeks prior the surgery, and following surgery as well. They showed that 98% of the patients remained continuously free of the condition with a median time on study of 31 months.

Once again this emphasizes the importance of referring a child with osteosarcoma to an oncologist for the latest advice before immediately suggesting an amputation.

The fourth contribution to this symposium deals with "Pediatric Brain Tumors" and is authored by Dr. Russell W. Walker and Dr. Jeffrey C. Allen, both of the Department of Pediatric Neuro-oncology of the Memorial Sloan-Kettering Cancer Center where Dr. Walker is a Fellow and Dr. Allen is an Associate Attending Physician. These are the most common solid tumors in children, so those of us with fairly large practices have had one or more of these malignancies develop in the children under our care. Most of these are incurable, although I have had the good fortune to have had two children with astrocytomas where total removal resulted in complete cure.

The authors discuss the clinical findings relative to the location of these tumors, and diagnostic aids such as the CT scan and the use of an intravenous contrast material to enhance the appearance of the lesion.

The four methods of treatment are next mentioned - surgery, radiation therapy, chemotherapy and corticosteroids.

The remainder of the article is given to a review of specific infratentorial and supratentorial tumors and their treatment. One important area of the discussion is given to CNS side effects of the therapy, whether it be by radiation or chemotherapy.

This excellent article leads to the hope that in the nottoo-distant future, therapy may become more effective, hopefully leading to an eventual cure of most cases.

The final paper is on "Rhabdomyosarcomas" and has been written by Dr. Fereshteh Ghavimi, Attending Pediatrician of the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York City. The author notes that these are the most common soft tissue sarcomas in children under 15 years of age, with approximately 70% presenting before the age often years.

Dr. Ghavimi emphasizes the importance of staging the patients with this condition, for treatment depends on the extent of the disease. Unfortunately most patients have advanced stages of the disease when first diagnosed. The clinical symptoms of these sarcomas vary with the location of the primary site and the sites of metastases.

Present combination therapy of surgery, radiation and modern chemotherapeutic drugs have greatly improved the survival rate of children with rhabdomyosarcomas, especially when diagnosed in the early stages. However, delayed side effects from such treatment occasionally occur.

This whole issue of Pediatric Annals once again emphasizes two important precepts for every pediatrician. The first is the need for careful examination for detection of malignancies in their earliest stages, and the second is the importance of sending all malignancies to a center of oncology for the latest treatment.

10.3928/0090-4481-19830501-01

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