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	ABSTRACT

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
Background. This article discusses the nasopharyngeal carcinoma (NPC) of American baseball icon Babe Ruth, as well as the diagnosis and treatment of NPC.

Case Description. NPC is a tumor originating from the epithelium of the nasopharynx. It is the leading form of cancer in certain well-defined populations in areas such as southern China, Southeast Asia, the Arctic, North Africa and the Middle East; it is relatively rare in the United States. Despite the fact that Babe Ruth’s family was of German descent and NPC is not prevalent in Germany, reports regarding Ruth’s autopsy demonstrate that his head and neck cancer was NPC.

Clinical Implications. Dentists play a pivotal role in the recognition of oral signs and symptoms and in the diagnosis of NPC, as well as the subsequent oral care of patients during and after treatment.

Key Words: Babe Ruth; nasopharyngeal carcinoma; Epstein-Barr virus

Abbreviations: CN: Cranial nerve • EBV: Epstein-Barr virus • HLA: Human leukocyte antigen • IMRT: Intensity-modulated radiation therapy • NPC: Nasopharyngeal carcinoma • RT: Radiation therapy • TMD: Temporomandibular disorder

Much is known about the life of the great American baseball player Babe Ruth. His life and activities, both on and off the field, have been well-chronicled. His farewell address, delivered at Yankee Stadium while he was dying of cancer, has become part of American folklore. There have been many misconceptions about Babe Ruth’s illness—primarily, that he had laryngeal carcinoma. He, in fact, had a cancer, relatively rare in the United States, known as nasopharyngeal carcinoma (NPC).

	BABE RUTH: A BIOGRAPHICAL SKETCH AND A CASE REPORT

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
Early life. On February 6, 1895, George Herman Ruth Jr. was born in Baltimore to parents of German descent. George and his sister Mary were the only two of eight children to survive past infancy.

As a youngster, George started to use tobacco and drink alcohol. He once said, "I learned early to drink beer, wine, whiskey, and I think I was about five when I first chewed tobacco."¹ In June 1902, his father brought seven-year-old George Jr. to St. Mary’s Industrial School for Boys and signed over custody to the Xaverian Brothers there, because he was labeled as incorrigible and the family could not handle his behavior.²

The prefect of discipline at St. Mary’s, Brother Mathias, turned young George’s life around. Not only did he show the boy love and caring, he also introduced him to the game he loved himself—baseball. During the 12 years George spent at St. Mary’s, his extraordinary baseball talent became evident. By the time George was 10 years old, he was playing on the school’s varsity baseball team, which was composed mostly of 15-year-old boys.

Career. At 19 years of age, George signed a contract with one of the most well-known baseball scouts of the day, Jack Dunn.^3,4 Dunn also legally adopted George to circumvent the St. Mary’s rule specifying that he was required to remain at the school until he was 21 years of age. Dunn was the owner and manager of the Baltimore Orioles, which was, at that time, a minor league team of the Boston Red Sox. Members of the team referred to George as "Jack’s newest babe." From that point forward, George Herman Ruth Jr. became known as "Babe Ruth."

Babe Ruth made his major league debut in July 1914 at Boston’s Fenway Park as a pitcher in a game against the Cleveland Indians. In January 1920, Boston Red Sox owner Harry Frazee sold Ruth’s contract to the New York Yankees for $100,000 and a substantial loan.³ Before Ruth came to the Yankees, they had not been a very successful team.³ During his first few years with them, the Yankees played at the New York Giants’ home field, the Polo Grounds, but Ruth was so popular and drew such large crowds that it caused the Giants’ owner to become jealous, and he asked the Yankees to leave. The Yankees opened their own stadium in April 1923, and it immediately was dubbed "the house that Ruth built."²

During his career, Ruth struggled with his weight. Professional baseball players of that time did not value exercise as today’s do. Also, smoking and drinking were much more prevalent and not frowned on by management as they would be today.²

Illness and death: a case report. Throughout the summer of 1946, Ruth experienced intense left retro-orbital pain. In September of that year, Ruth was admitted to French Hospital in New York City. At this point, the entire left side of his face was swollen, and his left eye was completely closed. The physicians diagnosed his condition as either toothache or sinusitis. Treatment consisted of penicillin and the extraction of three teeth.⁵ This treatment provided no relief, and in November physicians at French Hospital diagnosed his condition as Horner syndrome when a radiograph revealed a large mass at the base of his skull extending from the foramen ovale to the jugular foramen.⁵ Radiation therapy (RT) was administered without further diagnostic work-up. As Ruth had a history of heavy alcohol and tobacco (cigars and snuff) consumption, his physicians made a diagnosis of laryngeal carcinoma.

When Ruth underwent RT in November, it relieved some of his neurological symptoms. However, in December, a mass appeared in the left side of his neck. Surgical resection of the tumor was unsuccessful because it wrapped around the external carotid artery. After the surgery, Ruth’s voice was soft and low, and because he was unable to swallow, he required a feeding tube.

In June 1947, after Ruth received another course of RT as well as a course of female hormone therapy, oncologist Dr. Richard Lewisohn began daily injections of teropterin, which would be the precursor of the future class of chemotherapeutic drugs known as "folic acid antagonists" (amethopterin, now known as methotrexate).^5–7 Ruth had responded dramatically well to this treatment; the tumor mass in his neck disappeared, he gained weight, and he experienced less hoarseness and a significant decrease in facial pain. Unfortunately, this improvement was short-lived, and he returned to the hospital in June 1948. There he received more RT and underwent implantation of radiated gold seeds into his neck.⁵

On Aug. 16, 1948, Ruth was admitted to Memorial Hospital in New York, where he died of a right-sided lobar pneumonia secondary to the carcinoma. His autopsy revealed that he had had not laryngeal carcinoma but NPC. The primary site of the disease was the superior part of the nasopharynx (nose and mouth); however, it had metastasized to the lymph nodes on the left side of his neck, one lung, his liver, both of his adrenal glands and cranial nerves (CNs) 9, 19 and 11, which it surrounded. His larynx was normal on examination.

	NASOPHARYNGEAL CARCINOMA

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
NPC, the cancer that took Babe Ruth’s life, is a relatively rare cancer in the United States. Here we provide an overview of the condition.

Anatomy of the nasopharynx. The nasopharynx is the superior portion of the pharynx lying above the soft palate. It communicates with the nasal cavity anteriorly through the choanae. The lateral walls are formed by the eustachian tube and the fossa of Rosenmüller. The roof is surrounded by the pharyngeal hypophysis, the pharyngeal tonsil and the pharyngeal bursa, with the base of the skull above. The posterior boundary is formed by the muscles of the posterior pharyngeal wall. Inferiorly, the nasopharynx ends at an imaginary horizontal line formed by the upper surface of the soft palate and the posterior pharyngeal wall. NPC usually originates in the lateral wall of the nasopharynx.

Epidemiology. NPC is a rare tumor arising from the epithelium of the nasopharynx and is considered a variant of squamous cell carcinoma. It is relatively uncommon in the United States, with an incidence of less than 1 percent of all cancers.^8,9 However, it is a leading form of cancer in a few well-defined populations, including middle-aged natives of southern China, Southeast Asia, the Arctic, North Africa and the Middle East.¹⁰ The cause of increased risk of developing NPC in these regions is not entirely understood. The incidence is lower in northern China and Japan. The estimated number of deaths attributable to NPC worldwide annually exceeds 50,000, making it the 23rd most common cancer in the world.¹¹ The distinctive racial/ethnic and geographic distribution of NPC worldwide suggests that both environmental factors and genetic traits contribute to its development.¹⁰ NPC occurs more commonly in men than in women, and the peak age of diagnosis is between 50 and 59 years, decreasing thereafter.¹²

Risk factors. The primary risk for NPC most likely is multifactorial; those factors include viruses, consumption of salted fish,¹³ genetic factors and environmental factors.¹⁴ NPCs (also known as lymphoepitheliomas) have high Epstein-Barr virus (EBV)^15,16 antibody titer and an overexpression of the B-cell CLL/lymphoma 2 product. All NPCs are associated with EBV-latent gene products, unlike other head and neck carcinomas, including laryngeal carcinoma. The presence of EBV nuclear antigen 1 in peripheral blood cells denotes a significantly higher risk of developing distant metastases and a lower survival rate.¹⁷

Specific human leukocyte antigen (HLA) allele subtypes or combinations of alleles may carry particular risk of development of NPC.¹⁸ HLA-E has been reported as having a possible role through natural killer cell or cytotoxic lymphocyte function.¹⁹ Additionally, researchers found HLA-A2, B14 and B46 to be positively correlated with NPC but that HLA-A11, B13 and B22 were negatively correlated.¹⁹

Inhaled carcinogens—including fumes, smoke and chemicals in areas with poor ventilation—may be an important risk factor for development of NPC.²⁰ A history of disease of the ear, nose and throat may be associated with an increased risk of developing NPC.²⁰ In the United States, among whites, smoking and alcohol use generally have not been implicated as risk factors²¹; however, there may be an association,²¹ and further research is needed.

Oral signs and symptoms and diagnosis. In the United States, routine screening for NPC, which involves a blood test for EBV and visualization of the nasopharynx with an endoscope, is not conducted and not indicated because the disease is rare here. Rather, the focus here is on the signs and symptoms at diagnosis. NPC often is misdiagnosed in its early stages because its symptoms are vague and because of the difficulty of examining the nasopharynx.²² The first observable sign of the disease may be metastases to the cervical lymph nodes and involvement of the CNs, which indicates advanced disease. On examination, Babe Ruth had lymphadenopathy of the parotid and submandibular glands. According to Skinner and Van Hasselt,²³ the mean delay from the onset of the first symptom to diagnosis is six months. A patient may seek dental treatment for facial pain, a mass in the neck or trismus.²⁴ The dentist should be familiar with the signs and symptoms of NPC; this would help achieve an early diagnosis.^24,25 A differential diagnosis is temporomandibular joint disorder. These diseases share similar signs and symptoms, including trismus and facial pain (in the head, ear and jaw) (Box).^23,26

 
If the clinician suspects a diagnosis of NPC, fiber-optic endoscopy is essential so that he or she can view the nasopharynx and obtain a biopsy specimen, which is challenging because the tumor usually either is hidden, is too small or has spread. Once the diagnosis is confirmed, adjunctive tests are performed to determine the stage or metastasis of the cancer. These adjunctive tests include computed tomographic scan, magnetic resonance imaging, bone scan and lymph node biopsy. In the United States, NPC is classified into five stages depending on the extent of metatastsis (Table 1).²⁶

View this table: [in this window] [in a new window]   TABLE 1 Stages of nasopharyngeal carcinoma.*

 
Course of invasion. Tumor invasion into the skull base occurs in approximately 25 percent of cases and may lead to CN deficit.²⁷ CN VI (the abducens nerve) and CN V (the trigeminal nerve), in that order, are most commonly involved,²⁸ followed by CN III (the oculomotor nerve) and CN IV (the trochlear nerve). Patients with involvement of CN III, IV and VI demonstrate changes in ocular motion. Intracranial spread may occur via direct extension from the base of the skull or via perineural spread. Perineural spread usually affects branches of the trigeminal nerve.²⁹ Downward extension of the tumor into the palate may lead to referred ear pain caused by involvement of the trigeminal nerve. Trigeminal neuropathy is one of the most observable neurological manifestations of NPC.²⁹

In November 1946, Ruth was found to have paralysis of the left soft palate. Severe facial pain, including pain around the eye such as Ruth experienced, indicates trigeminal nerve involvement. Pain due to involvement of the sensory fibers of the trigeminal nerve usually precedes motor fiber involvement.

Babe Ruth’s complaints of difficulty in chewing and dysphagia may have been due to trismus, which occurs with direct invasion of the medial or lateral pterygoid muscles, involvement of CN XI (spinal accessory nerve) (which controls swallowing movements), CN V (which innervates the muscles of mastication) or both.

When a tumor infiltrates the pterygoid muscles, the infratemporal fossa is at risk. The maxillary sinus and orbits may be involved with invasion of the tumor from the pterygoid muscles. This explains Ruth’s complaints of left frontal headaches and diagnosis of sinusitis, which resulted in the inappropriate extraction of three teeth.

Ruth’s tumor had encircled the internal carotid artery. It also may have invaded through the foramen lacerum into the cavernous sinus. Symptoms of this invasion include ophthalmoplegia due to the involvement of CNs III, IV and VI and facial numbness caused by involvement of CN V.

Ruth was diagnosed as having Horner syndrome in November 1946. Horner syndrome occurs with injury to the cervical sympathetic chain, and more extensive skull base involvement produces deficits of the lower CNs (IX, X, XI, XII).³⁰

Current treatment modalities. Treatment options, which depend on the stage of the disease, include RT, intensity-modulated radiation therapy (IMRT), chemotherapy, chemoradiotherapy and surgery^22,24,30,31 (Table 2). Owing to the anatomical position of the nasopharynx, surgical intervention is difficult.³⁰ The most important immediate outcome of NPC treatment is control of the cancer at its initial primary site at the back of the nose.

View this table: [in this window] [in a new window]   TABLE 2 Options for treatment of nasopharyngeal carcinoma based on stage of disease.*

 
In curative therapy, RT is directed principally to this site and to the surrounding tissues and lymph nodes. For early-stage NPC (stage I or II), RT is used as the only treatment; thus, its success depends on the accurate delivery of radiation beams.^31,32 The RT doses delivered to the head and neck region are high, and the surrounding normal tissues—such as salivary glands, the temporal lobe, the spinal cord and optic nerves—are exposed to potential long-term adverse effects of RT.

IMRT is an advanced mode of high-precision RT that uses computer-controlled x-ray accelerators to deliver precise radiation doses. Conventional RT irradiates both parotid glands because they are in the pathway of radiation, resulting in irreversible xerostomia. IMRT conforms high-dose radiation to the tumor while conforming low-dose radiation to normal tissue, thus preserving the salivary glands and maintaining salivary function and quality of life.³³

Unfortunately, even with RT, the overall five-year survival rate is only 41 percent.³² Small early-stage (stages I and II) lesions are highly curable by means of RT, with survival rates of 60 to 80 percent^31,34; however, most cases are not diagnosed early enough.²⁵ Patients with moderately advanced stage III lesions treated by means of RT have shown five-year survival rates of about 46 percent.³⁵ Patients with advanced stage IV lesions—especially those associated with clinically positive cervical lymph nodes, CN involvement and bone destruction—have disease that is poorly controlled locally by RT with or without surgery, and the lesions often develop distant metastases despite local control.³⁶ Such patients have a five-year survival rate of about 30 percent.³³ Thus, because of the low cure rates with RT alone, various combinations of RT and chemotherapy may be superior to RT alone, with respect to overall survival, for patients who have advanced NPC.^25,37–40

Oral complications during and after treatment. The incidence of xerostomia and osteoradionecrosis may be reduced with the use of IMRT. However, the incidence of mucositis and osteoradionecrosis caused by the use of altered fractionation RT and higher total doses of RT and reirradiation persists. Thus, oral health care before, during and after therapy is important. Other oral complications due to RT include candidiasis, taste alterations, weight loss, dysphagia and trismus.²⁶

	DISCUSSION

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
NPC is difficult to diagnose because of the anatomical inaccessibility of the nasopharynx, the nonspecific nature of symptoms when the disease is in its early stages and the predisposition of the tumor to spread submucosally, making it clinically difficult to see on direct inspection. After a biopsy specimen is obtained and histology and imaging studies are performed to aid in diagnosis, the treatment of choice is RT, IMRT and chemoradiotherapy, while surgery is reserved for advanced cases. Ruth most likely was the first cancer patient to receive sequential RT and chemotherapy for NPC.⁴¹

Ruth wrote concerning the experimental injections of teropterin, "I realized that if anything was learned about that type of treatment, whether good or bad, it would be of use in the future to the medical profession and maybe to people with my same trouble."⁴¹ This statement led The Wall Street Journal to feature as its lead story of Sept. 11, 1947, an account of Dr. Lewisohn’s presentation of this case, which concluded that researchers might be on the verge of a cure for cancer.⁴¹

	NASOPHARYNGEAL CARCINOMA: THE DENTIST’S ROLE

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
Dentists are integral in the treatment of patients with NPC, especially in the process of referring such patients to the proper medical specialists. The patient may demonstrate symptoms such as a mass in the neck, trismus, or neck and facial pain that should alert the dentist to the possibility of NPC and the need for referral.

Advanced NPC mimics symptoms of temporomandibular disorders (TMDs) and laryngeal carcinoma. Both Babe Ruth’s physician and the public thought that he had laryngeal carcinoma, as evidenced by his symptom of hoarseness, due to tobacco use (in the form of cigars, chewing tobacco and snuff) and to heavy alcohol consumption. While tobacco and alcohol use have not been considered to be risk factors for NPC in Asian populations, their role in NPC is far less understood for white populations.

A differential diagnosis of NPC is TMD. While the two conditions have similar oral signs and symptoms, it is important that the dentist rule out TMD by recognizing other signs and symptoms unique to NPC.

In addition, dentists should be part of the patient’s health care team before, during and after treatment. The dentist will be involved in managing the care of a patient with NPC before, during and after radiation and chemotherapy. The patient must undergo a dental examination before initiating radiation therapy and chemotherapy. The dentist also will see the patient during and after treatment. During this time, the patient may experience xerostomia, caries and radiation mucositis.

	CONCLUSION

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 
The dentist plays an important role in the oral care of the patient with NPC. At the same time that the patient’s medical team is preparing the cancer treatment plan, the dentist should assess the patient’s oral needs before he or she undergoes treatment, especially radiotherapy. Thereafter, the dentist should monitor the patient for signs of xerostomia, oral mucositis, taste changes, infection, candidiasis and caries and should treat accordingly. The dentist should do everything possible to provide adequate oral care and to maintain the patient’s quality of life during treatment.

Babe Ruth now rests in Gate of Heaven Cemetery in Hawthorne, N.Y., with his wife, Claire. His grave still is visited, more than 50 years after his death, by many people who leave notes and gifts. On Ruth’s gravestone are the words of Cardinal Francis Joseph Spellman, archbishop of New York from 1939 through 1967: "May the divine spirit that animated Babe Ruth to win the crucial game of life inspire the youth of America."

	FOOTNOTES

Dr. Weinberg is a clinical associate professor, Department of Periodontology and Implant Dentistry, New York University College of Dentistry, New York City.

Disclosures. Drs. Maloney and Weinberg did not report any disclosures.

	REFERENCES

TOP ABSTRACT BABE RUTH: A BIOGRAPHICAL... NASOPHARYNGEAL CARCINOMA DISCUSSION NASOPHARYNGEAL CARCINOMA: THE... CONCLUSION REFERENCES

 

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