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Diagnosis and treatment of testicular tumors
Diagnosis and Treatment Testicular Tumors
of
COL. JOHN F. PATTON, MC, USA, CAPT. DAVID N. SEITZMAN,MC, USA AND CAPT. ROBERT A. ZONE, MC, USA, Washington, D. C. From tbe Urology Service, Department of Surgery, Walter Reed Army Hospital, Wasbington, D. C.
oping sperm as we11 as act as a supporting framework. They may aIso be the source of estrogens produced by the testes [5]. The interstitia1 ceIIs, or ceIIs of Leydig, secrete androgens which stimuIate and maintain the maIe sexua1 characteristics and induce enIargement of the penis and the secondary sex glands. The major androgen is testosterone, the most potent and perhaps the onIy androgen produced. Androgenic compounds are present in the urine of a11 norma persons, both maIe and femaIe. They are minima1 in quantity during the preadoIescent period, readiIy demonstrabIe in aduIt Iife, and tend to decrease with senescence. The interstitial ceIIs are stimuIated by the Iuteinizing hormone secreted by the anterior Iobe of the pituitary. There is a strong reciproca1 action between the pituitary and the gonads, and the testes act as a contro1 for the sexua1 function of the anterior pituitary. EIimination of androgens by castration resuIts in ceIIuIar changes in the hypophysis and an increase in urinary gonadotrophin excretion. PrepuberaI castration resuIts in the familiar picture of eunuchoidism. Castration in the aduIt never causes regression to the preadoIescent state but certain changes occur, particuIarIy in the young aduIt. The prostate and semina1 vesicIes undergo atrophy but there is Iittle or no decrease in the size of the penis, hair distribution remains essentiaIIy the same and there is no voice change. Libido and the abiIity to have erections may persist. Administration of androgens to the maIe castrate restores the norma histoIogy of the pituitary and reduces excessive urinary gonadotrophin excretion. Such repIacement therapy may be provided in the form of testosterone propionate or methy testosterone. The influence of androgens upon the intact testis is a contro-
HIS paper is concerned with the cIinicaI aspects of the management of tumors of the testis. The great majority are highIy mahgnant, metastasize earIy and the mortaIity is considerabIe; as a group, they comprise the most common form of maIignancy encountered in the young aduIt maIe. These facts emphasize the urgency for earIy diagnosis and prompt therapy. The materia1 presented herein is based on a study of 570 patients with testicuIar tumors treated at the Waiter Reed Army HospitaI from January I, 1940 to January I, 1959. AIthough the various types of tumors wiI1 be discussed brieffy in certain aspects of their behavior, we are concerned chieffy with the tumors of germina1 ceI1 origin.
T
FUNDAMENTALCONSIDERATIONS For a proper understanding of the origin and behavior of testicuIar tumors, a basic knowledge of the embryoIogy, anatomy and physioIogy of these structures is essentia1. It seems pertinent at this point, to present briefly those features which are reIevant to this discussion. For a more detaiIed review, the reader is referred to numerous texts on the subject [1,4]. The function of the testes is twofold: (I) production of spermatozoa, and (2) eIaboration of hormones. InvoIved in these processes are three types of ceIIs: the germ ceIIs, SertoIi ceIIs and the interstitia1 or ceIIs of Leydig. The germ ceIIs and SertoIi ceIIs are found within the tubuIes of the testis. Spermatogenesis begins at puberty and is provoked and maintained by the foIIicIestimuIating hormone secreted by the anterior Iobe of the pituitary. The SertoIi ceIIs are thought to provide nourishment for the deveI525
American
Journal
of Surgery,
Volume
gg, April,
rg6o
Patton,
Seitzman
versiaI subject and not fuIIy understood. Administration of testosterone propionate may stimuIate production of spermatozoa but in some instances wiI1 cause reduction of the sperm count, presumabIy by inhibition of pituitary secretion of gonadotrophins. There are many facets of this compIex subject of hypophyseaI-gonada reIationship which are not understood and the cIinica1 picture produced by hypo- or hypergonadism in many instances is d&cuIt to expIain. CLASSIFICATION
AND
ORIGIN
The cIassification of testicuIar tumors perhaps most wideIy accepted at the present time is that introduced and in use at the Armed Forces Institute of PathoIogy [z]. TesticuIar tumors may be divided into two broad categories, the germina1 and non-germina1. The germina1 tumors, which comprise 96.5 per cent of testicuIar tumors, are composed of one or any combination of four morphoIogic patterns, and may be divided into five groups : seminoma, embryona1 carcinoma, teratocarcinoma, teratoma and choriocarcinoma. A seminoma, which probabIy arises from the primordia1 germ ceI1, is composed of uniform ceIIs and does not seem to be intimateIy reIated to the other types. The other types, aIthough arising from the germ ceI1, show more potentiaIity, and embryona1 carcinoma appears to be the earIiest and most undifferentiated form. Further differentiation into choriocarcinoma with its cyto- and syncytia1 trophobIasts produces an extremeIy maIignant form of neoplasm. Somatic differentiation may occur to produce teratocarcinoma and teratoma with their recognizabIe feta1 and aduIt structures. The germina1 tumors may be further cIassifIed cIinicaIIy according to their response to radiation. A seminoma is sensitive to x-ray therapy and the others are highIy resistant. Non-germina1 tumors account for onIy 3.5 per cent of testicuIar neopIasms, and incIude the foIIowing: (I) interstitia1 or Leydig ceI1 tumors; (2) SertoIi ceI1 tumors; (3) tumors arising from supporting tissues, such as Iymphosarcomas and other types which have their counterparts in other regions of the body; and (4) those tumors of specific gonadal stroma. The last three groups are extremeIy rare and the stroma tumors, in particuIar, present many problems of histogenesis [9].
526
and Zone HORMONAL
ACTIVITY
Gonadotrophins are found normaIIy in the urine, and the aduIt maIe wiI1 excrete between 6 and approximateIy 50 mouse units per twenty-four hours. In the presence of a testicuIar tumor the titer may range from 200 to as high as 50,000 mouse units per day. ApproximateIy 85 per cent of a11 testicuIar tumors wiI1 show a positive A-Z test. In generaI, the more differentiated the tumor, the greater its output of hormone in the urine. Hamburger [3] was the first to describe the urinary gonadotrophins in testicuIar tumors and found two types: foIIicIe-stimulating hormones and chorionic gonadotrophins. The A-Z test provides a quantitative determination but does not distinguish between the two types. Further assay is necessary to measure the quantity of chorionic gonadotrophins, an important factor in those tumors showing syncytia1 eIements. In choriocarcinoma, chorionic gonadotrophins are excreted in the urine in Iarge amounts. In a seminoma, the range of the foIIicIe-stimuIating hormone excreted may vary from 400 to IO,000 mouse units per Iiter of urine. Both types of gonadotrophins may be excreted by the same tumor and this presumabIy depends upon the morphoIogic eIements present. There is very IittIe correIation between the histoIogic appearance of testicuIar tumors and the rate of hormona1 excretion as determined by the A-Z test. This has been shown by TwombIy and others [12], and has been noted in our own series. The A-Z determination, however, is usefu1 as a prognostic sign and an indicator of response to therapy. A return to norma IeveIs foIIowing orchiectomy is a weIcome finding. In some patients the titer may remain eIevated for an indefinite period foIIowing treatment without cIinica1 evidence of recurrence of the tumor. FaiIure to return to norma IeveIs, however, or to show some decrease, shouId be regarded with suspicion, and a continuous rise in any case is an ominous sign. Gynecomastia is not an unusua1 finding associated with testicuIar tumors and may occur with aImost any type. It is thoroughIy unpredictabIe, however, and the expIanation is often not apparent. The breast is a sensitive end organ and may respond to smaI1 increases in circulating gonadotrophins, but even high IeveIs do not aIways result in gynecomastia. GerminaI tumors often produce gonado-
Testicdar
Tumors in twenty-one). Six of these had undergone previous orchiopexy. It is we11 documented that the cryptorchid testis is more Iikely to undergo mahgnant degeneration than the norma scrota1 testis. It is likewise we11 accepted that successful orchiopexy does not Iessen the chance of maIignancy. These facts should be considered when there is a question as to whether the undescended testis in a given patient should be treated by orchiopexy or removal of the testis. Five of the patients in this series had biIateraI tumors. In one patient an interstitia1 cell tumor occurred in both testes simuItaneousIy. In the other four patients a tumor deveIoped in the opposite testis at intervaIs of from one to fourteen years, two of the same type and two of different types. This high incidence of one in I 14 patients justifies our opinion that there is a much greater probabiIity of a tumor deveIoping in the remaining testis of persons who have had a testicuIar tumor than there is in norma maIes who have never had a testicuIar tumor. Likewise it points up an important consideration in the follow-up examination.
trophins but even when present in Iarge amounts, physica changes are unusual. When somatic changes occur, such as gynecomastia, the features are usually not prominent and do not constitute a cIinica1 problem or aIter the course of therapy. The stroma tumors likewise present no endocrine probIem, but are equaIIy interesting from this standpoint. The tumors of chief bioIogic interest are the interstitia1 ceI1 tumors and SertoIi ceI1 tumors. The Leydig or interstitia1 ceIIs are concerned with the production of androgens, and their tumors may stimulate various bodiIy changes. InterstitiaI ceII tumors in chiIdren produce precocious sexua1 and somatic deveIopment. In the aduIt, the increased androgen IeveIs produce IittIe change, as the secondary sex characteristics are we11 estabIished. Gynecomastia and loss of libido are the major findings but are present in only a smaI1 number. Sertoli ceI1 tumors are extremeIy rare and with the Iimited number of reported cases, physical changes are not we11 estabIished. In generaI, however, they foIIow the pattern of other feminizing testicuIar neopIasms in that changes are inconsistent. INCIDENCE
AND
METASTASIS
DATA
TesticuIar tumors metastasize IargeIy by way of the Iymphatics, with the exception of choriocarcinoma which spreads by the hematogenous route. The Iungs are the next most frequent site of distant invoIvement. Metastasis occurs aIong the Iymphatic pathways which accompany the interna spermatic vesseIs in the cord, passing to the retroperitonea1 periaortic and pericava1 nodes to the IeveI of the renaI pedicles and above. The inguinal and femora1 nodes are not important unIess there is IocaI spread with extension to the scrotum or spermatic tunics. Local involvement, however, when present, portends a grave prognosis. As a ruIe, spread to the retroperitoneal nodes is Iimited to the affected side. However, not infrequentIy crossed metastasis occurs and the incidence is sufficient to warrant biIatera1 lymphadenectomy. In an anaIysis of 5 I0 patients, seventy-one (13.9 per cent) had demonstrabIe metastasis on admission as determined by physica examination, x-ray fiIm or urographic study. Fortyeight patients (9.4 per cent) showed no cIinica1 evidence of metastasis on admission, but on attempted Iymphadenectomy were found to have inoperabIe conditions. Thus, a tota of I 19
Tumors of the testis have an incidence of Iess than one in 50,ooo males, and represent approximateIy I per cent of a11 mahgnant tumors of maIes. They occur more frequentIy in the young aduIt maIe and comprise the most common form of mahgnancy encountered in patients from twenty to thirty-five years of age. Distribution of the 570 patients as to type of tumor is as foIIows: seminoma, 206 cases (36.1 per cent) ; embryona1 carcinoma, 177 (31.1 per cent); teratocarcinoma, 149 (26.1 per cent) ; teratoma, fourteen (2.5 per cent); choriocarcinoma, ten (I .8 per cent) ; interstitia1 ceI1, six (I per cent) ; and misceIIaneous, eight (I .4 per cent). The tumors in the misceIIaneous group incIude mesothehoma, Iymphosarcoma, rhabdosarcoma, adenomatoid tumor and undifferentiated sarcoma. The average age of 510 patients was 27.9 years. The youngest was three years of age and the eldest was fifty-seven. Seminomas occur in somewhat older persons, with an average age in this series of 30.7 years. EmbryonaI carcinoma and teratocarcinoma occurred at an average age of 26. I and 26.6 years, respectively. The tumor appeared in a cryptorchid testis in twenty-seven patients, or 4.7 per cent (one 527
Patton, Seitzman and Zone patients, is not considered an etioIogic factor. Rather it is thought to be coincident4 in attracting the patient’s attention to a preexisting Iesion. The duration of symptoms is shown in TabIe II. Sixty-five per cent of the patients had symptoms for Iess than six months, whiIe more than one-third had symptoms ranging from six months to more than two years. The average period for the entire series of patients, from the onset of symptoms to the time of definitive therapy, was approximateIy five months.
TABLE I SYMPrOMS (491 CASES) Symptom
No. of Cases I
Sweiling ................... Hardness or “Iump”. ....... No pain ................... Pain ....................... Symptoms of spread ......... No symptoms (routine examination). ................. History of trauma ...........
Per cent
I---74 22
365 Iog I25 IIf 47
25 23 IO
23 35
5 7
DIAGNOSIS
patients (23.3 per cent) had gross metastasis when first seen. The over-a11 mortaIity for the I Ig patients was more than 92 per cent. The preceding figures do not in&de those cases in which Iymphadenectomy was successfuIIy accompIished but the nodes were found to be positive. SYMPTOMS
The symptoms associated with tumors of the testis vary considerabIy and are often misIeading. Table I Iists the symptoms experienced by 491 of the 570 patients. The majority compIained of the presence of a painIess sweIIing or hardness of the testis. Absence of pain, however, is not a constant feature; in fact, aImost an equa1 number had pain in varying degrees. Pain, when present, is usuaIIy not severe and is probabIy expIained by hemorrhage within the testis. A sensation of “heaviness” in the scrotum is a frequent compIaint. Ten per cent of the patients initiaIIy had symptoms indicating spread of the disease. Five per cent had no symptoms whatever, and the Iesion in the testis was found on routine examination. A history of trauma, aIthough present in 7 per cent of the
TABLE INITIAL
Duration*
OF
SYMPTOMS
(442
III
-
(5 IO
CASES)
-
1No. of Cases i I‘er cent --
Tumor. ..................... None stated ................. E rroneous. ..................
CASES)
/No.ofCasesI
DIAGNOSIS
Diagnosis
TABLE II DURATION
The history reIated to tumors of the testis is thoroughIy unreIiabIe and one must depend upon careful examination of the scrota1 contents for a diagnosis. The mortaIity rate in patients with testicuIar tumors is exceedingIy high. Surgery and x-ray therapy have improved the outIook but the technics in both fieIds have about reached their maximum degree of refinement. With our present methods of treatment, the greatest hope in reducing the mortaIity lies in earIier diagnosis. From the figures presented in the preceding paragraph, it can readiIy be seen that this opportunity exists. The testis is an externa1 organ and, except in cryptorchism, is readily accessibIe for minute examination. Why, then, is there a deIay in diagnosis? The patient’s procrastination in seeking medica attention, of course, is a contributing factor over which we have no contro1. Perhaps some type of discreet educationa program might be devised. In many cases the
Percent
Epididymitis .............. “Nothing”. ............... Hydrocele................. Orchitis. .................. HematoceIe............... Torsion. .................. Seminal vesicIe. ........... Varicoceie................. cyst. .....................
16.3 %:i 1.6
2 I
.
. .
I I I I
-
528
46.3 25.5
83 r9 13 8
Rupture .................. * Average, 4 months, 28 days.
28.2
I44 236 r3o
.
-
Tes&uIar
Tumors
TABLE FIVE-YEAR
SURVIVAL:
IV
TOTAL SERIES
(389
CASES FOLLOWED
UP) AIive or Dead without Tumor
Dead
No. of Cases
Type of Tumor
Alive From Tumor
Seminoma................ Embryonai carcinoma. ..... Teratocarcinoma. ......... Teratoma. ................ Choriocarcinoma. ......... Others. .................. Total.............................
...... ...... ...... ...... ...... ......
138 125 103 8 8 7
II
103 48 42 7 I 3
I
3%
tumor may produce no symptoms or the Iesion may be so smaII that it is not readity detected. Another, and important, source of deIay is that an appreciabIe number are not recognized as tumors on the initia1 examination. It can be seen in TabIe III that an erroneous diagnosis was made in more than one-fourth of the patients, epididymitis being the most common. Examination. As stated previousIy, the diagnosis wiI1 depend not on the history but on carefu1 examination. Variation in the size of the scrota1 contents may be noted on inspection. PaIpation of the testis shouId aIways be performed bimanualIy. A usefu1 ruIe of thumb is to examine the opposite, supposedly norma testis prior to paIpation of the affected side. This wiI1 give the examiner a baseline for comparison. The epididymis normaIIy can be distinguished easily from the testis proper by careful palpation. The norma parenchyma of the testis is uniform in consistency and any mass or area of induration, whether sharpIy demarcated or iIIdetined, may be considered a tumor unti1 proved otherwise. Not infrequentIy the entire testis may be repIaced by the tumor, in which case the consistency wiI1 be firm to hard. Tenderness is usuaIIy absent but may be present to a miId or moderate degree. The epididymis wiI1 be normal except in those rare instances when the tumor may have spread by direct extension. If a hydrocele is present and proper evaIuation of the testis is made diffIcuIt, carefu1 aspiration should be performed to permit more accurate paIpation. The differentia1 diagnosis includes any and a11 conditions the scrota1 contents may demonstrate.
529
204
Other Cause
I
70 57
24 7 4
I
0
7 4
0
150
0
I
Total
Per cent
‘27 55 46 7 I
92.0 44.0 44.7 87.5 12.5
3 _______
57-I
35
239
61.4
The genera1 physica examination incIudes paIpation of the abdomen for evidence of metastasis, a careful search for Iymphadenopathy and examination of the breasts. A paIpabIe Ieft supracIavicuIar node may be the first cIinica1 evidence of metastasis. Laboratory Studies. In addition to the routine tests, the work-up shouId incIude x-ray films of the chest, excretory urograms, a quantitative A-Z test, sedimentation rate and pIateIet count. Special hormona1 studies are desirabIe. A skeIeta1 survey may be made if desired but metastasis to bone is exceedingIy rare. If the diagnosis remains doubtfu1 after carefu1 examination, the testis shouId be expIored. This is performed through an inguina1 incision, occIuding the cord with a rubber-shod cIamp before delivering the testis into the wound for inspection. If doubt stiI1 exists, the testis shouId be removed. Aspiration biopsies shouId never be performed and open biopsies are equaIIy hazardous. RESULTS
OF THERAPY
TabIe IV shows the five-year surviva1 rate and incIudes the resuIts in a11 types and combinations of treatment. One hundred two of 389 patients had demonstrable metastasis on admission or were found to have inoperabIe conditions on attempted Iymphadenectomy. An additiona fifty-one had positive nodes on Iymphadenectomy, making a tota of 153 (39.3 per cent) who had proved spread of their disease at the time treatment was instituted. The
Patton, TABLE COMPOSITE
TABLE
OF
SURVIVING
Seitzman
hemorrhagic areas. When the type of tumor has been established, further treatment is then outIined, and wiI1 depend, of course, on the presence or absence of metastasis. The practice of extending the inguina1 incision at the time of orchiectomy to palpate the retroperitonea1 space for evidence of Iymph node invoIvement is, in our opinion, unreIiabIe and not justified. Lymph nodes may be invoIved but not paIpabIe, and even if paIpabIe may show onIy reactive hyperpIasia on microscopic section. Only gross invoIvement can be detected by bIind paIpation and even then wiII not necessariIy indicate operabiIity. Radiation. The vaIue of radiation therapy in the treatment of seminomas of the testis is we11 known. One can expect a cure in approximateIy gs per cent of patients by treatment with orchiectomy and radiation aIone, appIied in a dosage of 2,000 r. EmbryonaI carcinomas and teratocarcinomas are highly radioresistant, and the dosage required is much greater. AIthough we include radiation in the treatment of these tumors, its vaIue is diffrcuIt to assess. In our series of 127 patients treated by orchiectomy and radiation aIone, none of those with Iymph node metastasis responded to radiation and a11 died within two years. The morbidity associated with the appIication of Iarge dosages of roentgen rays may be considerabIe, and compIications with Iate sequeIae are not infrequent. As applied to the treatment of the radioresistant tumors, it must be considered in the reaIm of radica1 therapy. RetroperitoneaI IymLymphadenectomy. phadenectomy shouId be performed in a11 cases of maIignant radioresistant tumors of the testis except choriocarcinoma. This appIies, of course, onIy in the absence of cIinica1 metastasis. Lymphadenectomy shouId be biIatera1 in a11 cases, as a significant number show invoIvement of the contraIatera1 nodes. BiIateraI dissection has been performed at Walter Reed Army HospitaI since 1954. During the past two years a transperitonea1 approach has been used [8]. This has definite advantages, in our opinion, over other incisions used in the past. It provides good access to the critica area around the renaI pedicIes on both sides and permits adequate simuItaneous biIatera1 dissection. One has good control of the major vesseIs if by chance they are injured during the procedure. The operative time is considerabIy reduced because of better exposure and the time
v
PER
CENT
OF
PATIENTS
FIVEYEARS
Lymphadenectomy (243)
TOd Type
of Tumor
sem1noma.. . Embryomd carcinoma. Teratocarcinome. Teratoma Total,
Group
Radiation Therapy
(389)
(127)
92.0 44.0 44.7 87.5 6.14
86.1 13.0 17.7
~
Total
Positive Nodes
tive Nodes
96.0
72.7
98.9
72.3 60.6
65.0 30.0
75.6 73.9 85.7
52.9
86.5
l00.0 ___-
85.7
35.4
79.4
and Zone
Nega-
resuIts may be interpreted in the Iight of these figures. TabIe v is a composite tabIe, and the surviva1 rate figures for the various types of tumors are given in percentages. The number of patients for each type is not shown. The majority of the 127 patients treated by radiation had known metastasis when treatment was instituted. Of 243 patients undergoing Iymphadenectomy, aII but sixteen received radiation therapy. TREATMENT
Tumors of the testis shouId be treated as surgica1 emergencies. Any patient with a scrota1 Iesion admitted to the urologica ward, regardless of the admitting diagnosis, is seen promptIy by a member of the uroIogy staff. If a tumor of the testis is suspected, preIiminary studies are obtained on an emergency basis and the patient is taken directIy to the operating room. Orchiectomy. AIthough some aspects of the treatment of testicuIar tumors remain controversia1, there is genera1 agreement that high orchiectomy shouId be performed through an inguina1 incision and the cord severed at the IeveI of the interna inguina1 ring. FoIIowing remova of the testis with its tunics, the inguina1 canal shouId be cIeaned of a11 Ioose fat and connective tissue and the stump of the cord Iikewise freed of surrounding attachments. It is a good practice to fix the Iigated stump of the cord to the roof of the cana with a suture of pIain catgut to prevent retraction. We prefer to wait for a study of the permanent pathoIogic sections rather than to proceed with Iymphadenectomy at this time. MuItipIe sections of the tumor are cut to incIude any unusua1 or 530
Testicdar
Tumors
saved in opening and cIosing the wound. A tota of twenty-eight node dissections by this route have been performed to date. There have been no deaths and the morbidity is so minimal as to justify the removal of this procedure from the reaIm of radicalism. (Fig. I.) Cbemotberupy. This therapeutic field hoIds promise but as yet is in the earIy stages of deveIopment. Numerous compounds are under investigation in various clinics and an active program is in progress at our own institution. Our experience during the past two years has produced some encouraging resuIts, but a report at this time would seem premature. PLAN
OF TREATMENT
The current policy for treatment of testicuIar tumors at the Waiter Reed Army Hospital is as foIIows: I. Seminoma. Orchiectomy is foIIowed by radiation of the entire lymphatic chain. This includes the abdomen, mediastinum and supraclavicular region, giving a tota tumor dose of 2,000 r to each area. Lymphadenectomy is not considered necessary for seminomas but if the microscopic sections show anapIasia or the diagnosis of “pure” seminoma is doubtful, Iymphadenectomy is performed prior to radiation.
Embryonal and Teratoma. 2.
Carcinoma,
FIG. I. RetroperitoneaI space at compIetion of Iymphadenectomy. I. Vena cava. 2. Aorta. 3. Right kidney. 4. Right ureter. 5. L.eft renaI vein. 6. Inferior mesenteric artery. 7. Bifurcation of aorta.
with chemotherapy. Chemotherapy offers the onIy hope in the presence of metastasis. 4. Non-germinal Tumors. The treatment of the wide variety of neoptasms in the reIativeIy smaI1 group of non-germina1 tumors is not incIuded in this discussion. In generaI, however, orchiectomy alone is performed; Iymphadenectomy and/or radiation are applied only in specific cases. 5. Follow-up Examinations. AI1 patients with testicuIar tumors are examined at periodic intervaIs over an indefinite period.
Teratocarcinoma
In the absence of cIinica1 metastasis, orchiectomy is foIIowed by biIatera1 Iymphadenectomy performed through a transperitonea1 approach. If the nodes removed are negative pathoIogicaIIy, no further therapy, such as radiation, is given. If any of the nodes removed revea1 metastasis, or if at the time of surgery the patient was found to have an inoperabIe condition and onIy a biopsy specimen could be obtained, postoperative radiation is applied to the entire Iymphatic chain, incIuding the Ieft SupracIavicuIar area, mediastinum and abdomen. A tumor dose of 4,000 r is deIivered to each of these areas over an average period of I IO days, beginning with the upper abdomina1 porta1. An exposure of 4,000 r is considered the upper Iimit of safety. AI1 radiation is given with the miIIion-voIt therapy equipment. Treatment in advanced cases, or in those patients who return with metastasis, consists of chemotherapy and other measures. 3. Choriocarcinoma. Patients with choriocarcinoma are treated by orchiectomy aIone or
SUMMARY I. Tumors of the testis are reIativeIy uncommon but are among the most maIignant of the body. In patients from twenty to thirty-five years of age, they comprise the most common form of maIignancy encountered, and reap a heavy to11 of life. At least four of ten of these young adult maIes wiII die of the disease. This fact emphasizes the importance of earIy detection and prompt therapy. 2. The germina1 tumors comprise more than
531
Patton, Seitzman and Zone 95 per cent of a11 testicular tumors and in&de the most malignant types. HormonaI activity is present in the majority, as demonstrated by gonadotrophin excretion, but physica changes are unusual. There is poor correIation between the histoIogic picture and the rate of gonadotrophin excretion. HormonaI assays of the urine, however, are of definite vaIue in indicating response to therapy and as a guide to prognosis. 3. EarIy diagnosis is imperative and offers the best opportunity for reducing the present excessive mortaIity. An average of five months eIapsed in this series between the onset of symptoms and the institution of therapy. This deIay was due in part (25 per cent) to an erroneous diagnosis at the time of initial examination. One shouId acquaint himseIf with the anatomy of the scrotum and be abIe to paIpate its contents accurateIy. TesticuIar tumors shouId be considered surgica1 emergencies. 4. Seminomas are radiosensitive and one can expect a cure rate of over go per cent by orchiectomy and radiation aIone. However, the microscopic sections shouId be carefuIIy studied for the presence of other eIements and if doubt exists, Iymphadenectomy is indicated. 5. The treatment of the radioresistant tumors (embryona1 carcinomas, teratocarcinomas and teratomas) shouId incIude retroperitonea1 and biIatera1 dissection Iymphadenectomy, shouId be performed in a11 cases. 6. The transperitonea1 approach to the retroperitonea1 space, in our opinion, offers definite advantages over other incisions. It
provides good access to the critica area around the renaI vessels on both sides and permits simukaneous biIatera1 resection.
REFERENCES
H. A. PrincipIes of SurgicaI Physiology. New York, 1957. Paul B. Hoeber, Inc. 2. DIXON, F. J. and MOORE, R. A. TesticuIar tumors: clinicopathologic study. Cancer, 6: 427, 1953. 3. HAMBURGER,C., BANG, F. and NIELSON, J. Studies on gonadotrophin hormones in cases of testicular tumors. Acta patb. et microbial. scandinau., 13: 75, I.
DAVIS,
1936. 4. HOWARD, J. E. and Scorn, W. W. In: WiIIiams’ Textbook of EndocrinoIogy, chapt. 5, p. 316. PhiIadeIphia, rg5o. W. B. Saunders Co. 5. HUGGINS,C. and MOULDER, P. V. Estrogen production by SertoIi cell tumors of the testis. Cancer Res., 5: 510, 1945. 6. LEADBE~TER, W. F., FEELEY, J. R. and WHEELER, J. S. TesticuIar tumors: summarized data and suggested plan of treatment. In: Urological Survey, vo1. I, p. 447. Baltimore, 1951. WiIIiams & WiIkins Co. 7. LEWIS, L. G. RadicaI orchiectomy for tumors of the testis. J. A. M. A., 137: 828, 1948. 8. MALLIS, N. and PATTON, J. F. Transperitoneal biIatera1 Iymphadenectomy in testis tumor. J. Ural., 80: 501, 1958. 9. MOSTOFI, F. K., THEISS, E. A. ~~~ASHLEY, D. J. B. Tumors of speciaIized gonada stroma in human maIe patients. Cancer, 12: 944, 1959. IO. PA-I-~oN,J. F. and MALLIS, N. Tumors of the testis. J. Ural., 81: 457, 1959. II. TWOMBLY, G. H. The reIationship of hormones to testicuIar tumors. Surgery, 16: 181, 1944. 12. TWOMBLY, G. H., TEMPLE, H. M. and DEAN, A. L. CIinicaI value of the Ascheim-Zondek test in the diagnosis of testicular tumors. J. A. M. A., I 18: 106, 1942.
532
of
COL. JOHN F. PATTON, MC, USA, CAPT. DAVID N. SEITZMAN,MC, USA AND CAPT. ROBERT A. ZONE, MC, USA, Washington, D. C. From tbe Urology Service, Department of Surgery, Walter Reed Army Hospital, Wasbington, D. C.
oping sperm as we11 as act as a supporting framework. They may aIso be the source of estrogens produced by the testes [5]. The interstitia1 ceIIs, or ceIIs of Leydig, secrete androgens which stimuIate and maintain the maIe sexua1 characteristics and induce enIargement of the penis and the secondary sex glands. The major androgen is testosterone, the most potent and perhaps the onIy androgen produced. Androgenic compounds are present in the urine of a11 norma persons, both maIe and femaIe. They are minima1 in quantity during the preadoIescent period, readiIy demonstrabIe in aduIt Iife, and tend to decrease with senescence. The interstitial ceIIs are stimuIated by the Iuteinizing hormone secreted by the anterior Iobe of the pituitary. There is a strong reciproca1 action between the pituitary and the gonads, and the testes act as a contro1 for the sexua1 function of the anterior pituitary. EIimination of androgens by castration resuIts in ceIIuIar changes in the hypophysis and an increase in urinary gonadotrophin excretion. PrepuberaI castration resuIts in the familiar picture of eunuchoidism. Castration in the aduIt never causes regression to the preadoIescent state but certain changes occur, particuIarIy in the young aduIt. The prostate and semina1 vesicIes undergo atrophy but there is Iittle or no decrease in the size of the penis, hair distribution remains essentiaIIy the same and there is no voice change. Libido and the abiIity to have erections may persist. Administration of androgens to the maIe castrate restores the norma histoIogy of the pituitary and reduces excessive urinary gonadotrophin excretion. Such repIacement therapy may be provided in the form of testosterone propionate or methy testosterone. The influence of androgens upon the intact testis is a contro-
HIS paper is concerned with the cIinicaI aspects of the management of tumors of the testis. The great majority are highIy mahgnant, metastasize earIy and the mortaIity is considerabIe; as a group, they comprise the most common form of maIignancy encountered in the young aduIt maIe. These facts emphasize the urgency for earIy diagnosis and prompt therapy. The materia1 presented herein is based on a study of 570 patients with testicuIar tumors treated at the Waiter Reed Army HospitaI from January I, 1940 to January I, 1959. AIthough the various types of tumors wiI1 be discussed brieffy in certain aspects of their behavior, we are concerned chieffy with the tumors of germina1 ceI1 origin.
T
FUNDAMENTALCONSIDERATIONS For a proper understanding of the origin and behavior of testicuIar tumors, a basic knowledge of the embryoIogy, anatomy and physioIogy of these structures is essentia1. It seems pertinent at this point, to present briefly those features which are reIevant to this discussion. For a more detaiIed review, the reader is referred to numerous texts on the subject [1,4]. The function of the testes is twofold: (I) production of spermatozoa, and (2) eIaboration of hormones. InvoIved in these processes are three types of ceIIs: the germ ceIIs, SertoIi ceIIs and the interstitia1 or ceIIs of Leydig. The germ ceIIs and SertoIi ceIIs are found within the tubuIes of the testis. Spermatogenesis begins at puberty and is provoked and maintained by the foIIicIestimuIating hormone secreted by the anterior Iobe of the pituitary. The SertoIi ceIIs are thought to provide nourishment for the deveI525
American
Journal
of Surgery,
Volume
gg, April,
rg6o
Patton,
Seitzman
versiaI subject and not fuIIy understood. Administration of testosterone propionate may stimuIate production of spermatozoa but in some instances wiI1 cause reduction of the sperm count, presumabIy by inhibition of pituitary secretion of gonadotrophins. There are many facets of this compIex subject of hypophyseaI-gonada reIationship which are not understood and the cIinica1 picture produced by hypo- or hypergonadism in many instances is d&cuIt to expIain. CLASSIFICATION
AND
ORIGIN
The cIassification of testicuIar tumors perhaps most wideIy accepted at the present time is that introduced and in use at the Armed Forces Institute of PathoIogy [z]. TesticuIar tumors may be divided into two broad categories, the germina1 and non-germina1. The germina1 tumors, which comprise 96.5 per cent of testicuIar tumors, are composed of one or any combination of four morphoIogic patterns, and may be divided into five groups : seminoma, embryona1 carcinoma, teratocarcinoma, teratoma and choriocarcinoma. A seminoma, which probabIy arises from the primordia1 germ ceI1, is composed of uniform ceIIs and does not seem to be intimateIy reIated to the other types. The other types, aIthough arising from the germ ceI1, show more potentiaIity, and embryona1 carcinoma appears to be the earIiest and most undifferentiated form. Further differentiation into choriocarcinoma with its cyto- and syncytia1 trophobIasts produces an extremeIy maIignant form of neoplasm. Somatic differentiation may occur to produce teratocarcinoma and teratoma with their recognizabIe feta1 and aduIt structures. The germina1 tumors may be further cIassifIed cIinicaIIy according to their response to radiation. A seminoma is sensitive to x-ray therapy and the others are highIy resistant. Non-germina1 tumors account for onIy 3.5 per cent of testicuIar neopIasms, and incIude the foIIowing: (I) interstitia1 or Leydig ceI1 tumors; (2) SertoIi ceI1 tumors; (3) tumors arising from supporting tissues, such as Iymphosarcomas and other types which have their counterparts in other regions of the body; and (4) those tumors of specific gonadal stroma. The last three groups are extremeIy rare and the stroma tumors, in particuIar, present many problems of histogenesis [9].
526
and Zone HORMONAL
ACTIVITY
Gonadotrophins are found normaIIy in the urine, and the aduIt maIe wiI1 excrete between 6 and approximateIy 50 mouse units per twenty-four hours. In the presence of a testicuIar tumor the titer may range from 200 to as high as 50,000 mouse units per day. ApproximateIy 85 per cent of a11 testicuIar tumors wiI1 show a positive A-Z test. In generaI, the more differentiated the tumor, the greater its output of hormone in the urine. Hamburger [3] was the first to describe the urinary gonadotrophins in testicuIar tumors and found two types: foIIicIe-stimulating hormones and chorionic gonadotrophins. The A-Z test provides a quantitative determination but does not distinguish between the two types. Further assay is necessary to measure the quantity of chorionic gonadotrophins, an important factor in those tumors showing syncytia1 eIements. In choriocarcinoma, chorionic gonadotrophins are excreted in the urine in Iarge amounts. In a seminoma, the range of the foIIicIe-stimuIating hormone excreted may vary from 400 to IO,000 mouse units per Iiter of urine. Both types of gonadotrophins may be excreted by the same tumor and this presumabIy depends upon the morphoIogic eIements present. There is very IittIe correIation between the histoIogic appearance of testicuIar tumors and the rate of hormona1 excretion as determined by the A-Z test. This has been shown by TwombIy and others [12], and has been noted in our own series. The A-Z determination, however, is usefu1 as a prognostic sign and an indicator of response to therapy. A return to norma IeveIs foIIowing orchiectomy is a weIcome finding. In some patients the titer may remain eIevated for an indefinite period foIIowing treatment without cIinica1 evidence of recurrence of the tumor. FaiIure to return to norma IeveIs, however, or to show some decrease, shouId be regarded with suspicion, and a continuous rise in any case is an ominous sign. Gynecomastia is not an unusua1 finding associated with testicuIar tumors and may occur with aImost any type. It is thoroughIy unpredictabIe, however, and the expIanation is often not apparent. The breast is a sensitive end organ and may respond to smaI1 increases in circulating gonadotrophins, but even high IeveIs do not aIways result in gynecomastia. GerminaI tumors often produce gonado-
Testicdar
Tumors in twenty-one). Six of these had undergone previous orchiopexy. It is we11 documented that the cryptorchid testis is more Iikely to undergo mahgnant degeneration than the norma scrota1 testis. It is likewise we11 accepted that successful orchiopexy does not Iessen the chance of maIignancy. These facts should be considered when there is a question as to whether the undescended testis in a given patient should be treated by orchiopexy or removal of the testis. Five of the patients in this series had biIateraI tumors. In one patient an interstitia1 cell tumor occurred in both testes simuItaneousIy. In the other four patients a tumor deveIoped in the opposite testis at intervaIs of from one to fourteen years, two of the same type and two of different types. This high incidence of one in I 14 patients justifies our opinion that there is a much greater probabiIity of a tumor deveIoping in the remaining testis of persons who have had a testicuIar tumor than there is in norma maIes who have never had a testicuIar tumor. Likewise it points up an important consideration in the follow-up examination.
trophins but even when present in Iarge amounts, physica changes are unusual. When somatic changes occur, such as gynecomastia, the features are usually not prominent and do not constitute a cIinica1 problem or aIter the course of therapy. The stroma tumors likewise present no endocrine probIem, but are equaIIy interesting from this standpoint. The tumors of chief bioIogic interest are the interstitia1 ceI1 tumors and SertoIi ceI1 tumors. The Leydig or interstitia1 ceIIs are concerned with the production of androgens, and their tumors may stimulate various bodiIy changes. InterstitiaI ceII tumors in chiIdren produce precocious sexua1 and somatic deveIopment. In the aduIt, the increased androgen IeveIs produce IittIe change, as the secondary sex characteristics are we11 estabIished. Gynecomastia and loss of libido are the major findings but are present in only a smaI1 number. Sertoli ceI1 tumors are extremeIy rare and with the Iimited number of reported cases, physical changes are not we11 estabIished. In generaI, however, they foIIow the pattern of other feminizing testicuIar neopIasms in that changes are inconsistent. INCIDENCE
AND
METASTASIS
DATA
TesticuIar tumors metastasize IargeIy by way of the Iymphatics, with the exception of choriocarcinoma which spreads by the hematogenous route. The Iungs are the next most frequent site of distant invoIvement. Metastasis occurs aIong the Iymphatic pathways which accompany the interna spermatic vesseIs in the cord, passing to the retroperitonea1 periaortic and pericava1 nodes to the IeveI of the renaI pedicles and above. The inguinal and femora1 nodes are not important unIess there is IocaI spread with extension to the scrotum or spermatic tunics. Local involvement, however, when present, portends a grave prognosis. As a ruIe, spread to the retroperitoneal nodes is Iimited to the affected side. However, not infrequentIy crossed metastasis occurs and the incidence is sufficient to warrant biIatera1 lymphadenectomy. In an anaIysis of 5 I0 patients, seventy-one (13.9 per cent) had demonstrabIe metastasis on admission as determined by physica examination, x-ray fiIm or urographic study. Fortyeight patients (9.4 per cent) showed no cIinica1 evidence of metastasis on admission, but on attempted Iymphadenectomy were found to have inoperabIe conditions. Thus, a tota of I 19
Tumors of the testis have an incidence of Iess than one in 50,ooo males, and represent approximateIy I per cent of a11 mahgnant tumors of maIes. They occur more frequentIy in the young aduIt maIe and comprise the most common form of mahgnancy encountered in patients from twenty to thirty-five years of age. Distribution of the 570 patients as to type of tumor is as foIIows: seminoma, 206 cases (36.1 per cent) ; embryona1 carcinoma, 177 (31.1 per cent); teratocarcinoma, 149 (26.1 per cent) ; teratoma, fourteen (2.5 per cent); choriocarcinoma, ten (I .8 per cent) ; interstitia1 ceI1, six (I per cent) ; and misceIIaneous, eight (I .4 per cent). The tumors in the misceIIaneous group incIude mesothehoma, Iymphosarcoma, rhabdosarcoma, adenomatoid tumor and undifferentiated sarcoma. The average age of 510 patients was 27.9 years. The youngest was three years of age and the eldest was fifty-seven. Seminomas occur in somewhat older persons, with an average age in this series of 30.7 years. EmbryonaI carcinoma and teratocarcinoma occurred at an average age of 26. I and 26.6 years, respectively. The tumor appeared in a cryptorchid testis in twenty-seven patients, or 4.7 per cent (one 527
Patton, Seitzman and Zone patients, is not considered an etioIogic factor. Rather it is thought to be coincident4 in attracting the patient’s attention to a preexisting Iesion. The duration of symptoms is shown in TabIe II. Sixty-five per cent of the patients had symptoms for Iess than six months, whiIe more than one-third had symptoms ranging from six months to more than two years. The average period for the entire series of patients, from the onset of symptoms to the time of definitive therapy, was approximateIy five months.
TABLE I SYMPrOMS (491 CASES) Symptom
No. of Cases I
Sweiling ................... Hardness or “Iump”. ....... No pain ................... Pain ....................... Symptoms of spread ......... No symptoms (routine examination). ................. History of trauma ...........
Per cent
I---74 22
365 Iog I25 IIf 47
25 23 IO
23 35
5 7
DIAGNOSIS
patients (23.3 per cent) had gross metastasis when first seen. The over-a11 mortaIity for the I Ig patients was more than 92 per cent. The preceding figures do not in&de those cases in which Iymphadenectomy was successfuIIy accompIished but the nodes were found to be positive. SYMPTOMS
The symptoms associated with tumors of the testis vary considerabIy and are often misIeading. Table I Iists the symptoms experienced by 491 of the 570 patients. The majority compIained of the presence of a painIess sweIIing or hardness of the testis. Absence of pain, however, is not a constant feature; in fact, aImost an equa1 number had pain in varying degrees. Pain, when present, is usuaIIy not severe and is probabIy expIained by hemorrhage within the testis. A sensation of “heaviness” in the scrotum is a frequent compIaint. Ten per cent of the patients initiaIIy had symptoms indicating spread of the disease. Five per cent had no symptoms whatever, and the Iesion in the testis was found on routine examination. A history of trauma, aIthough present in 7 per cent of the
TABLE INITIAL
Duration*
OF
SYMPTOMS
(442
III
-
(5 IO
CASES)
-
1No. of Cases i I‘er cent --
Tumor. ..................... None stated ................. E rroneous. ..................
CASES)
/No.ofCasesI
DIAGNOSIS
Diagnosis
TABLE II DURATION
The history reIated to tumors of the testis is thoroughIy unreIiabIe and one must depend upon careful examination of the scrota1 contents for a diagnosis. The mortaIity rate in patients with testicuIar tumors is exceedingIy high. Surgery and x-ray therapy have improved the outIook but the technics in both fieIds have about reached their maximum degree of refinement. With our present methods of treatment, the greatest hope in reducing the mortaIity lies in earIier diagnosis. From the figures presented in the preceding paragraph, it can readiIy be seen that this opportunity exists. The testis is an externa1 organ and, except in cryptorchism, is readily accessibIe for minute examination. Why, then, is there a deIay in diagnosis? The patient’s procrastination in seeking medica attention, of course, is a contributing factor over which we have no contro1. Perhaps some type of discreet educationa program might be devised. In many cases the
Percent
Epididymitis .............. “Nothing”. ............... Hydrocele................. Orchitis. .................. HematoceIe............... Torsion. .................. Seminal vesicIe. ........... Varicoceie................. cyst. .....................
16.3 %:i 1.6
2 I
.
. .
I I I I
-
528
46.3 25.5
83 r9 13 8
Rupture .................. * Average, 4 months, 28 days.
28.2
I44 236 r3o
.
-
Tes&uIar
Tumors
TABLE FIVE-YEAR
SURVIVAL:
IV
TOTAL SERIES
(389
CASES FOLLOWED
UP) AIive or Dead without Tumor
Dead
No. of Cases
Type of Tumor
Alive From Tumor
Seminoma................ Embryonai carcinoma. ..... Teratocarcinoma. ......... Teratoma. ................ Choriocarcinoma. ......... Others. .................. Total.............................
...... ...... ...... ...... ...... ......
138 125 103 8 8 7
II
103 48 42 7 I 3
I
3%
tumor may produce no symptoms or the Iesion may be so smaII that it is not readity detected. Another, and important, source of deIay is that an appreciabIe number are not recognized as tumors on the initia1 examination. It can be seen in TabIe III that an erroneous diagnosis was made in more than one-fourth of the patients, epididymitis being the most common. Examination. As stated previousIy, the diagnosis wiI1 depend not on the history but on carefu1 examination. Variation in the size of the scrota1 contents may be noted on inspection. PaIpation of the testis shouId aIways be performed bimanualIy. A usefu1 ruIe of thumb is to examine the opposite, supposedly norma testis prior to paIpation of the affected side. This wiI1 give the examiner a baseline for comparison. The epididymis normaIIy can be distinguished easily from the testis proper by careful palpation. The norma parenchyma of the testis is uniform in consistency and any mass or area of induration, whether sharpIy demarcated or iIIdetined, may be considered a tumor unti1 proved otherwise. Not infrequentIy the entire testis may be repIaced by the tumor, in which case the consistency wiI1 be firm to hard. Tenderness is usuaIIy absent but may be present to a miId or moderate degree. The epididymis wiI1 be normal except in those rare instances when the tumor may have spread by direct extension. If a hydrocele is present and proper evaIuation of the testis is made diffIcuIt, carefu1 aspiration should be performed to permit more accurate paIpation. The differentia1 diagnosis includes any and a11 conditions the scrota1 contents may demonstrate.
529
204
Other Cause
I
70 57
24 7 4
I
0
7 4
0
150
0
I
Total
Per cent
‘27 55 46 7 I
92.0 44.0 44.7 87.5 12.5
3 _______
57-I
35
239
61.4
The genera1 physica examination incIudes paIpation of the abdomen for evidence of metastasis, a careful search for Iymphadenopathy and examination of the breasts. A paIpabIe Ieft supracIavicuIar node may be the first cIinica1 evidence of metastasis. Laboratory Studies. In addition to the routine tests, the work-up shouId incIude x-ray films of the chest, excretory urograms, a quantitative A-Z test, sedimentation rate and pIateIet count. Special hormona1 studies are desirabIe. A skeIeta1 survey may be made if desired but metastasis to bone is exceedingIy rare. If the diagnosis remains doubtfu1 after carefu1 examination, the testis shouId be expIored. This is performed through an inguina1 incision, occIuding the cord with a rubber-shod cIamp before delivering the testis into the wound for inspection. If doubt stiI1 exists, the testis shouId be removed. Aspiration biopsies shouId never be performed and open biopsies are equaIIy hazardous. RESULTS
OF THERAPY
TabIe IV shows the five-year surviva1 rate and incIudes the resuIts in a11 types and combinations of treatment. One hundred two of 389 patients had demonstrable metastasis on admission or were found to have inoperabIe conditions on attempted Iymphadenectomy. An additiona fifty-one had positive nodes on Iymphadenectomy, making a tota of 153 (39.3 per cent) who had proved spread of their disease at the time treatment was instituted. The
Patton, TABLE COMPOSITE
TABLE
OF
SURVIVING
Seitzman
hemorrhagic areas. When the type of tumor has been established, further treatment is then outIined, and wiI1 depend, of course, on the presence or absence of metastasis. The practice of extending the inguina1 incision at the time of orchiectomy to palpate the retroperitonea1 space for evidence of Iymph node invoIvement is, in our opinion, unreIiabIe and not justified. Lymph nodes may be invoIved but not paIpabIe, and even if paIpabIe may show onIy reactive hyperpIasia on microscopic section. Only gross invoIvement can be detected by bIind paIpation and even then wiII not necessariIy indicate operabiIity. Radiation. The vaIue of radiation therapy in the treatment of seminomas of the testis is we11 known. One can expect a cure in approximateIy gs per cent of patients by treatment with orchiectomy and radiation aIone, appIied in a dosage of 2,000 r. EmbryonaI carcinomas and teratocarcinomas are highly radioresistant, and the dosage required is much greater. AIthough we include radiation in the treatment of these tumors, its vaIue is diffrcuIt to assess. In our series of 127 patients treated by orchiectomy and radiation aIone, none of those with Iymph node metastasis responded to radiation and a11 died within two years. The morbidity associated with the appIication of Iarge dosages of roentgen rays may be considerabIe, and compIications with Iate sequeIae are not infrequent. As applied to the treatment of the radioresistant tumors, it must be considered in the reaIm of radica1 therapy. RetroperitoneaI IymLymphadenectomy. phadenectomy shouId be performed in a11 cases of maIignant radioresistant tumors of the testis except choriocarcinoma. This appIies, of course, onIy in the absence of cIinica1 metastasis. Lymphadenectomy shouId be biIatera1 in a11 cases, as a significant number show invoIvement of the contraIatera1 nodes. BiIateraI dissection has been performed at Walter Reed Army HospitaI since 1954. During the past two years a transperitonea1 approach has been used [8]. This has definite advantages, in our opinion, over other incisions used in the past. It provides good access to the critica area around the renaI pedicIes on both sides and permits adequate simuItaneous biIatera1 dissection. One has good control of the major vesseIs if by chance they are injured during the procedure. The operative time is considerabIy reduced because of better exposure and the time
v
PER
CENT
OF
PATIENTS
FIVEYEARS
Lymphadenectomy (243)
TOd Type
of Tumor
sem1noma.. . Embryomd carcinoma. Teratocarcinome. Teratoma Total,
Group
Radiation Therapy
(389)
(127)
92.0 44.0 44.7 87.5 6.14
86.1 13.0 17.7
~
Total
Positive Nodes
tive Nodes
96.0
72.7
98.9
72.3 60.6
65.0 30.0
75.6 73.9 85.7
52.9
86.5
l00.0 ___-
85.7
35.4
79.4
and Zone
Nega-
resuIts may be interpreted in the Iight of these figures. TabIe v is a composite tabIe, and the surviva1 rate figures for the various types of tumors are given in percentages. The number of patients for each type is not shown. The majority of the 127 patients treated by radiation had known metastasis when treatment was instituted. Of 243 patients undergoing Iymphadenectomy, aII but sixteen received radiation therapy. TREATMENT
Tumors of the testis shouId be treated as surgica1 emergencies. Any patient with a scrota1 Iesion admitted to the urologica ward, regardless of the admitting diagnosis, is seen promptIy by a member of the uroIogy staff. If a tumor of the testis is suspected, preIiminary studies are obtained on an emergency basis and the patient is taken directIy to the operating room. Orchiectomy. AIthough some aspects of the treatment of testicuIar tumors remain controversia1, there is genera1 agreement that high orchiectomy shouId be performed through an inguina1 incision and the cord severed at the IeveI of the interna inguina1 ring. FoIIowing remova of the testis with its tunics, the inguina1 canal shouId be cIeaned of a11 Ioose fat and connective tissue and the stump of the cord Iikewise freed of surrounding attachments. It is a good practice to fix the Iigated stump of the cord to the roof of the cana with a suture of pIain catgut to prevent retraction. We prefer to wait for a study of the permanent pathoIogic sections rather than to proceed with Iymphadenectomy at this time. MuItipIe sections of the tumor are cut to incIude any unusua1 or 530
Testicdar
Tumors
saved in opening and cIosing the wound. A tota of twenty-eight node dissections by this route have been performed to date. There have been no deaths and the morbidity is so minimal as to justify the removal of this procedure from the reaIm of radicalism. (Fig. I.) Cbemotberupy. This therapeutic field hoIds promise but as yet is in the earIy stages of deveIopment. Numerous compounds are under investigation in various clinics and an active program is in progress at our own institution. Our experience during the past two years has produced some encouraging resuIts, but a report at this time would seem premature. PLAN
OF TREATMENT
The current policy for treatment of testicuIar tumors at the Waiter Reed Army Hospital is as foIIows: I. Seminoma. Orchiectomy is foIIowed by radiation of the entire lymphatic chain. This includes the abdomen, mediastinum and supraclavicular region, giving a tota tumor dose of 2,000 r to each area. Lymphadenectomy is not considered necessary for seminomas but if the microscopic sections show anapIasia or the diagnosis of “pure” seminoma is doubtful, Iymphadenectomy is performed prior to radiation.
Embryonal and Teratoma. 2.
Carcinoma,
FIG. I. RetroperitoneaI space at compIetion of Iymphadenectomy. I. Vena cava. 2. Aorta. 3. Right kidney. 4. Right ureter. 5. L.eft renaI vein. 6. Inferior mesenteric artery. 7. Bifurcation of aorta.
with chemotherapy. Chemotherapy offers the onIy hope in the presence of metastasis. 4. Non-germinal Tumors. The treatment of the wide variety of neoptasms in the reIativeIy smaI1 group of non-germina1 tumors is not incIuded in this discussion. In generaI, however, orchiectomy alone is performed; Iymphadenectomy and/or radiation are applied only in specific cases. 5. Follow-up Examinations. AI1 patients with testicuIar tumors are examined at periodic intervaIs over an indefinite period.
Teratocarcinoma
In the absence of cIinica1 metastasis, orchiectomy is foIIowed by biIatera1 Iymphadenectomy performed through a transperitonea1 approach. If the nodes removed are negative pathoIogicaIIy, no further therapy, such as radiation, is given. If any of the nodes removed revea1 metastasis, or if at the time of surgery the patient was found to have an inoperabIe condition and onIy a biopsy specimen could be obtained, postoperative radiation is applied to the entire Iymphatic chain, incIuding the Ieft SupracIavicuIar area, mediastinum and abdomen. A tumor dose of 4,000 r is deIivered to each of these areas over an average period of I IO days, beginning with the upper abdomina1 porta1. An exposure of 4,000 r is considered the upper Iimit of safety. AI1 radiation is given with the miIIion-voIt therapy equipment. Treatment in advanced cases, or in those patients who return with metastasis, consists of chemotherapy and other measures. 3. Choriocarcinoma. Patients with choriocarcinoma are treated by orchiectomy aIone or
SUMMARY I. Tumors of the testis are reIativeIy uncommon but are among the most maIignant of the body. In patients from twenty to thirty-five years of age, they comprise the most common form of maIignancy encountered, and reap a heavy to11 of life. At least four of ten of these young adult maIes wiII die of the disease. This fact emphasizes the importance of earIy detection and prompt therapy. 2. The germina1 tumors comprise more than
531
Patton, Seitzman and Zone 95 per cent of a11 testicular tumors and in&de the most malignant types. HormonaI activity is present in the majority, as demonstrated by gonadotrophin excretion, but physica changes are unusual. There is poor correIation between the histoIogic picture and the rate of gonadotrophin excretion. HormonaI assays of the urine, however, are of definite vaIue in indicating response to therapy and as a guide to prognosis. 3. EarIy diagnosis is imperative and offers the best opportunity for reducing the present excessive mortaIity. An average of five months eIapsed in this series between the onset of symptoms and the institution of therapy. This deIay was due in part (25 per cent) to an erroneous diagnosis at the time of initial examination. One shouId acquaint himseIf with the anatomy of the scrotum and be abIe to paIpate its contents accurateIy. TesticuIar tumors shouId be considered surgica1 emergencies. 4. Seminomas are radiosensitive and one can expect a cure rate of over go per cent by orchiectomy and radiation aIone. However, the microscopic sections shouId be carefuIIy studied for the presence of other eIements and if doubt exists, Iymphadenectomy is indicated. 5. The treatment of the radioresistant tumors (embryona1 carcinomas, teratocarcinomas and teratomas) shouId incIude retroperitonea1 and biIatera1 dissection Iymphadenectomy, shouId be performed in a11 cases. 6. The transperitonea1 approach to the retroperitonea1 space, in our opinion, offers definite advantages over other incisions. It
provides good access to the critica area around the renaI vessels on both sides and permits simukaneous biIatera1 resection.
REFERENCES
H. A. PrincipIes of SurgicaI Physiology. New York, 1957. Paul B. Hoeber, Inc. 2. DIXON, F. J. and MOORE, R. A. TesticuIar tumors: clinicopathologic study. Cancer, 6: 427, 1953. 3. HAMBURGER,C., BANG, F. and NIELSON, J. Studies on gonadotrophin hormones in cases of testicular tumors. Acta patb. et microbial. scandinau., 13: 75, I.
DAVIS,
1936. 4. HOWARD, J. E. and Scorn, W. W. In: WiIIiams’ Textbook of EndocrinoIogy, chapt. 5, p. 316. PhiIadeIphia, rg5o. W. B. Saunders Co. 5. HUGGINS,C. and MOULDER, P. V. Estrogen production by SertoIi cell tumors of the testis. Cancer Res., 5: 510, 1945. 6. LEADBE~TER, W. F., FEELEY, J. R. and WHEELER, J. S. TesticuIar tumors: summarized data and suggested plan of treatment. In: Urological Survey, vo1. I, p. 447. Baltimore, 1951. WiIIiams & WiIkins Co. 7. LEWIS, L. G. RadicaI orchiectomy for tumors of the testis. J. A. M. A., 137: 828, 1948. 8. MALLIS, N. and PATTON, J. F. Transperitoneal biIatera1 Iymphadenectomy in testis tumor. J. Ural., 80: 501, 1958. 9. MOSTOFI, F. K., THEISS, E. A. ~~~ASHLEY, D. J. B. Tumors of speciaIized gonada stroma in human maIe patients. Cancer, 12: 944, 1959. IO. PA-I-~oN,J. F. and MALLIS, N. Tumors of the testis. J. Ural., 81: 457, 1959. II. TWOMBLY, G. H. The reIationship of hormones to testicuIar tumors. Surgery, 16: 181, 1944. 12. TWOMBLY, G. H., TEMPLE, H. M. and DEAN, A. L. CIinicaI value of the Ascheim-Zondek test in the diagnosis of testicular tumors. J. A. M. A., I 18: 106, 1942.
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