The Surgical Treatment of Hodgkin's Disease

[CANCER RESEARCH 26 Part 1, 1254-1263, June 1966] The Surgical Treatment of Hodgkin's Disease

GEORGE T. PACK AND DAVID W. MOLANDER The Pack Medical Foundation, New York, New York

Summary matous, but it does not permit of detailed classification. If we stress this necessary minor surgery so strongly at this time, it is Re-evaluation of the role of radical surgery in the treatment of early Hodgkin's disease is proposed. The correct application for 3 reasons: (a) the incredible evidence that many physicians of surgical techniques for the diagnosis of Hodgkin's disease and in this present day ignore the presence of and do not remove an enlarged and obviously pathologic lymph node for biopsy, influ the treatment of complications and concurrent unrelated dis enced by the dangerous assumption that it is due to an inflam eases is elaborated. The acceptable indications and probable matory lymphadenitis; (6) some patients continue to be treated contraindications for radical extirpative dissection followed by a by irradiation and/or chemotherapy without histologie verifica full tumor dose of irradiation as the initial treatment of patients with unifocal Hodgkin's disease are discussed. tion of the diagnosis; (c) if such a lymph node were excised more frequently and earlier, the percentage of patients with Hodgkin's A significantly higher 10-year survival rate occurred in a limited number of patients with early Hodgkin's disease treated disease in unifocal Stage I would increase, thereby enlarging the opportunities for surgical treatment and greater curability initially with radical surgery and irradiation as compared with a group treated with irradiation only. Further re-examination of If suspicious peripheral lymph nodes do not exist, the surgeon may elect to perform an exploratory laparotomy to biopsy a this approach is justified. palpable mass of unknown character, although admittedly the majority of patients with retroperitoneal nodal Hodgkin's dis Introduction ease have definite enlargement of peripheral lymph nodes. In a series of 50 exploratory laparotomies for obscure abdominal In a legendary book on the natural history of Ireland, there diseases performed at the Memorial Hospital, only 4 were sub was purported to be a chapter listed in the table of contents as sequently labeled as futile in affording neither diagnosis nor "Snakes of Ireland," but on turning to the listed page number, the subject was disposed of with the laconic sentence: "There treatment (39). Thoracotomy is occasionally performed to biopsy a mediastinal or pulmonary mass of obscure nature. A prelimi are no snakes in Ireland." So today, some iconoclasts have inti nary scalene biopsy which reveals Hodgkin's disease would mated that "there is no surgical treatment of Hodgkin's disease" obviate the necessity for the more major thoracotomy since it and are inclined to refer all cases of this disease to the thera would offer presumptive evidence that the mediastinal lymph peutic disciplines of irradiation and chemotherapy. In the denial nodes were part of the same disease. of any indications for primary surgical treatment they could be 90% correct, but there are occasional settings in which surgical excision may serve beneficially as an ally of the more commonly Lymphangiographic Diagnosis employed modes of treatment (Table 1). It is essential not only to establish a definitive histologie diag nosis but also to determine by all possible means the probable Biopsy staging of the disease. In addition to radiographie visualization of chest and bones, medical surveys by physical examination, Three centuries have elapsed since Malpighi (20) in his "De blood counts and bone marrow studies, and scintigrams of bony Viscerum Structura" described the necropsy findings of nodular skeleton (radioactive fluorine-18) and liver (radioactive iodine- splenic lesions and lymphadenopathies characteristic of the 131 rose bengal), a minor surgical procedure known as lym- lymphoid disease to which we now apply the eponym, "Hodg phangiography may change the clinical staging of Hodgkin's dis kin's disease." Of the 7 cases originally described by Thomas ease from Stage I to Stage II. For example, by using a tiny No. Hodgkin in 1832 (14), only 3 would qualify today as truly repre 10 polyethylene catheter inserted into an intermetatarsal web sentative of the disease which bears his name. Regardless of lymphatic, made visible by a blue dye (alphazurine), a radio- specific signs and symptoms, the clinical diagnosis is never as paque liquid called Ethiodal (ethyl ester of iodized poppy seed accurate as a peripheral node biopsy. For the record, for future oil) is slowly injected by a small lymphangiogram pump [Ariel statistical evaluation, for the estimation of prognosis, for guid and Resnick (2)]. Visualization of the femoral, inguinal, iliac, ance in the choice of therapy, a biopsy is essential. It may be and paraaortic and paracaval nodes is achieved. Identification of accomplished most satisfactorily by the complete removal of a retroperitoneal Hodgkin's disease by this procedure has inhibited peripheral lymph node. Partial removal of a lymph node is us from performing groin dissections for erroneously labeled hazardous because the capsule is released and local spillage and unicentric disease (Stage I). Whenever the radiographie proce infiltration may occur. Aspiration biopsy is condemned; it may dure reveals a more advanced stage of this disease, Ariel has afford evidence to the pathologist that the lesion is lympho- continued the lymphatic infusion by substituting Ethiodal syn-

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thesized with radioactive iodine-131 and administered therapy in TABLE 2 doses of 20-40 me (Fig. 1). HODGKIN'S DISEASE: INITIAL LYMPHADENOPATHY

LymphadenopathyCervicalMediastinalAxillaryInguinalParaaorticMesenterioEpitrochlearPreauricularNasopharyngealMultipleTotalNo.ofpatients85524034161412622272%20.916.412.610.75.14.41.97.085.0 General Principles and Indications for Surgical Treatment

Williams et al. (38) have wisely considered 4 different condi tions under which surgery may be helpful to the patient with Hodgkin's disease: (a) surgery for diagnosis: peripheral node biopsy, even laparotomy or thoracotomy; (6) surgery for concur rent unrelated diseases, e.g., appendicitis; (c) surgery for com plications directly and indirectly related to Hodgkin's disease, such as hypersplenism, or compression of the spinal cord or trachea; (d) surgery for the definitive treatment of Hodgkin's disease per se. EVALUATION OF PROGNOSTIC FACTORS IN THE INDIVIDUAL PATIENT.Before subjecting the patient with Hodgkin's disease to the rigors of major surgen-, the acceptable indications and in tiding a patient with advanced Hodgkin's disease over the the probable contraindications should be fully evaluated. The surgical procedure. factors deemed favorable from the standpoint of a good prog STAGEi OR PHASEiâ€”UNICENTRICFOCUSOF HODGKIN'SDIS nosis are normal red blood cell and marrow cell counts; absence EASE.Stage I describes a unicentric focus of Hodgkin's disease of leukocytosis, leukopenia, eosinophilia, and thrombocyto- without constitutional symptomatology. In selected instances penia; lymphadenopathy localized to 1 region; early surgical within this group of patients, e.g., with either cervical, axillary, intervention for Stage I Hodgkin's disease; bulky local growth or groin lymphadenopathies, an initial surgical intervention may but remaining as a unicentric focus; and the histologie type of add many years to the life expectancy of the patient. If a surgi Hodgkin's disease with nodular sclerosis. Factors strongly sug cal attack cannot be applied, a no less aggressive approach with gesting that radical curative surgical efforts are contraindieated radiation therapy is indicated. In this stage of Hodgkin's disease, include the following states: rpimary abdominal Hodgkin's the best chance exists to prevent the malignant tumor from disease, Pel-Ebstein septic fever, fever concurrent with the very pursuing a progressive and, at times, intermittent and relent incipiency of the disease, splenomegaly, multiple regions of lessly malignant course. nodal involvement, severe pruritus, and antecedent acute infec Hodgkin's disease, as a disorder, may implicate the entire tion. Unfortunately, by the time the diagnosis is established reticuloendothelial system but, fortunately, may affect only a there are not too many patients free of 1 or more of the afore regional group of lymph nodes in its incipiency. In order of fre mentioned unfavorable factors. quency, the initial lymphadenopathies reported by our patients UNRELATED SURGICAL PROCEDURES IN PATIENTS WITH HODG- are as follows: cervical, mediastinal, axillary, inguinal, para- KIN'S DISEASE.Allthe usual unrelated surgical diseases and indi aortic, mesenteric, epitrochlear, preauricular, nasopharyngeal, cations which can afflict a group of otherwise normal people may and simultaneous multicentric regions (Table 2). The most funda occur in patients with Hodgkin's disease. Surgical procedures for mental concept here in the choice of future treatment is the cholelithiasis, appendicitis, lung abscess, bleeding ulcers, perfora realization that it may be a clinically localized disease and, tions of the gastrointestinal tract, even CesarÃansection for therefore, amenable to extirpative dissection (32). Such a uni dystocia must be done, employing the usual surgical indications. centric focus should be treated early in its development, and Bleeding and wound healing may require special attention. before dissemination occurs, either by complete regional dissec Transfusions of fresh whole blood and platelets may be helpful tion or by equally aggressive radiation therapy. Every diagnostic effort should be made to insure the unicentricity of this disease before venturing into a radical surgical approach. The number of TABLE 1 patients with Hodgkin's disease who fit into this favorable cate PERCENTAGEINCIDENCEOF VARIOUS MALIGNANTLYMPHOMAS" gory remains quite limited, but would increase many fold if earlier nodal biopsies were performed. For example, the present ing manifestations in 316 patients with Hodgkin's disease in oui- follicularlympho-6.76.44.611.6Lympho-sarcoma35.632.043.330.2Reticulum20.410.219.62.3sÃ©riesarelisted in Table 3. If the 159 patients who asserted that the initial manifestation of this disease was an enlarged lymph node in 1 of these 3 superficial regional groups (neck, axilla, Gall(13)Rosenberg, and Mallory groin) immediately had a peripheral node biopsy, the initial Diamond,Jaslowitz, therapy might well have been a radical node dissection and (24)Jackson and Graver greatly enhanced opportunity of cure for 50% of our patients. (10)Molanderand Parker Patients with Stage I Hodgkin's disease in whom the disease and PackHodgkin'sdisease37.051.232.034.6Giant has a slow evolutionary gamut do better with surgical treatment â€¢FromD.W. Molander and G. T. Pack (22), by courtesy of the than patients with a fulminating type of growth. Review of Surgery. Of course, there are surgical pessimists who assert that if a

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TABLE 3 sis with collagen, suggesting to Lukes that a relationship exists PRESENTINGMANIFESTATIONSIN316 PATIENTS between the sclerosing feature of this regional lesion and quies WITHHODGKIN'SDISEASE cent Hodgkin's disease. Because of the unusually good prognosis, perhaps venturesome surgeons should attempt more mediastinal ofpatients85)40^Â° manifestationPeripheralInitial dissections through sternotomy incisions in suitable subjects. nodes The Surgical Treatment of Unicentric (Stage I) CervicalAxillary 9)12.6>Â°Hodgkin's Disease in Peripheral Lymph Nodes

Inguinal 34J 10. 7J A physician cannot accurately assay the exact extent of MultipleTotalHead 22624252614166423316%20.7.057.21.9 Hodgkin's disease, but it is a serious error to assume the incur ability of the disease when it is palpably limited to 1 regional group of lymph nodes and so to delay treatment while watch andneckNasopharyngeal fully waiting for dissemination to become clinically evident. It is also improper to administer a sublethal dose of irradiation when PreauricuhirSkinSupraorhitalTotalThoracicMediastino]Lung;0.31.30.33.816.41.918.34.45.11.911.41.37.2influenced by this defeatist attitude. The thesis has been held by many physicians that Hodgkin's disease is a generalized sys temic ailment even from the moment of its inception. There is sufficient evidence and experience to refute this opinion. In the American Journal of Pathology, in 1942, Gall and Mallory (13) made the astute statement that "malignant lymphoma should not be regarded as a systemic disease at the onset, but as uni- pleuralTotalAbdominalMesenterioParaaorticGastrointestinal centric in origin, spreading into other foci at extremely variable rates." Stage I unifocal Hodgkin's disease of the neck, axilla, and groin may be successfully eradicated by aggressive total lymph node dissection. Diamond (9), an internist, attempted to instruct surgeons concerning the restrictions or limitations in selecting patients for radical surgical extirpation of regional node groups (vide infra). organTotalSkeletalOtheror specific With the disease unilateral in the neck, radical neck dissection was to be done only when the involved nodes were superior to an imaginary line bisecting the neck horizontally at the midpoint of another imaginary line drawn from the mastoid eminence of the temporal bone to the midportion of the clavicle. If the mass sitesTotalXo. was at or inferior to this axis point, surgery should not be the elected discipline. In the axilla, with Clinical Class or Phase I setting, dissection should be done only when the involved nodes 0 If the 159patients who asserted that the initial manifestation are confined to the lower portion of the armpit and not up near, or in, the apical region. In the groin, it was his advice to recom of this disease was an enlarged lymph node in 1 of these 3 super ficial regional groups immediately had a peripheral node biopsy, mend dissection only in Clinical Class I cases with palpable fem the initial therapy might well have been a radical node dissection oral nodes but no enlarged inguinal nodes. These arbitrary and greatly enhanced opportunity of cure for 50% of our patients. limitations and selected indications for surgery are mentioned here because they have been given wide publication. We cannot cervical or axillary lymph node contains Hodgkin's disease, then subscribe to these dicta because they would deny opportunities for cure. Slaughter (29), for example, has had a patient surviving intrathoracic nodes are likewise involved, and if inguinal nodes for 20 years who had retroclavicular node dissection. We know are proved positive, then paraaortic nodes are inevitably so af that Hodgkin's disease appearing first in supraclavicular nodes fected. The apparent truth of this dogmatic attitude is proved to may represent the classic signal nodes of Troisier-Virchow, be their own satisfaction by their procrastinating in the institution tokening cryptic intrathoracic or intraabdominal foci, but it is of correct and agressive therapy until such extensions do occur. not necessarily so and the patient should be given the benefit of Lukes (19) has stated that nodular sclerosis, a histologie type of Hodgkin's disease characterized by the formation of collagen, the chance. is associated with a high incidence of mediastinal involvement and appears to represent a regional expression of Hodgkin's Scope of Surgical ExÃ©resis disease. Nodular sclerosis was the most common histologie type Our scope of surgical exenteration for Clinical Class I of Hodg observed in Stage I of his series; the patients had a median kin's disease in the lymph nodes of the neck, axilla, and groin is survival of 11 years. Lukes states that in Stage I the frequency as follows: The radical neck dissection includes the removal of of the nodular type, as compared with other types, was 15 times the sternocleidomastoid, omohyoicl, and platysma muscles, the as great as all the other types combined. Evidently this histo internal jugular vein, the adventitial coat of the carotid artery, logie variety of Hodgkin's disease undergoes spontaneous sclero and all of the fat, lymphoid, and areolar tissues in the neck, in-

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Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1966 American Association for Cancer Research. Surgical Treatment eluding all the unilateral triangles. In dissecting the involved 6-14 years. The same group of patients are now well for 12-20 axilla, the pectoralis major and minor muscles are removed and years, with the exception of 1 patient who died of multiple the axilla freed of all lymph nodes from the apical region down to sclerosis in his llth postoperative year. Since the 1958 report, 16 and including the subscapular nodes, sparing only the long more patients have survived the 5-year interval after neck dis thoracic and subscapular nerves. In groin dissections, a liberal section. ellipse of skin is sacrificed, the skin flaps dissected widely back, LACHER(18). Lacher cited 11 cases from the Memorial Hos the inguinal ligament detached temporarily from the anterior pital, New York City, in which the patients had radical surgical superior spine, the retroperitoneum entered, and all lymph nodes dissection, with or without combined radiation therapy, for from the bifurcation of the aorta dissected downward to include Stage I Hodgkin's disease. Two patients having only surgerv all iliac, obturator, inguinal, and femoral groups (Fig. 2). Inas survived more than 5 years. Five patients who had surgery com much as the operative mortality is practically zero, why should bined with irradiation survived 5 years. The 5-year survival in the surgeon compromise on the scope of the exÃ©resis? this group was, therefore, 63.6%. Of the 93 patients with Stage If the regional node dissection is thorough, there should be no I Hodgkin's disease in the total group, which included a majority reasonable need for supplemental external radiation therapy. treated by irradiation alone, the 5-year survival was 65.6%, a Influenced by a combination of caution and fear, we have rou comparable salvage. tinely administered X-ray therapy after dissections of the neck, MOLANDERANDPACK. The end results of the 316 patients axilla, and groin for Hodgkin's disease. Postoperative irradiation treated in the Pack Medical Group are given in Tables 4-6. The should be given with the same dosage factors as for primary most significant observation here is obtained by a study of the irradiation of Hodgkin's disease. We have not used preliminary end results of Stage I patients. The 5-year end results secured by radiation therapy followed by dissection for 2 reasons: the subse surgical excision and radiation therapy are almost identical, but quent dissection is more technically difficult, and wound healing the 10-year survival, without recurrence in the interval, is over is impaired. Postirradiation dissection is indicated in some in whelmingly in favor of surgical treatment. stances for the removal of nodes which have become resistant to In this regard, it is our contention that the number of patients irradiation. Slaughter and Craver (30) stated that if the results with unifocal Hodgkin's disease suitable for radical node dissec of surgical therapy equal the results of irradiation, surgery should tion could be increased by 1000% if early peripheral node biopsy be used because the local effects of such operations are apt to were done shortly after the appearance of a painless, palpably remain permanent, whereas the side effects of irradiation not enlarged lymph node. only are permanent but also may be progressive. Splenectomy in Hodgkin's Disease Results of Surgical Treatment The end results of definitive surgical therapy for Clinical The consideration of possible surgical therapy involving re Class or Phase I Hodgkin's disease may be summarized from moval of the spleen in patienta with Hodgkin's disease entails 2 major problems: (o) the management of Hodgkin's disease in the several sources. GALL(12). Gall, in 1943, was the earliest advocate of surgical spleen either as a primary site or when splenic involvement is treatment for unifocal Hodgkin's disease. The median survival part of the systemic disease; and (b) splenectomy as a means of correcting the secondary hypersplenism which complicates the of the group treated surgically was 5.4 years, and of the group life history of Hodgkin's disease in some patients. treated by X-ray therapy, 3.2 years. None of the patients treated by surgery received postoperative irradiation. Surgical treatment The gross types of splenic involvement have been classified resulted in a 5-year survival rate of 41%. into 4 general groups by Ahmann et al. of the Mayo Clinic (1): WILLIAMSET AL. (38). In their group of 400 patients (240 (a) homogeneous enlargement, in which there is no discernible hospitalized for study and treatment), there was only 1 instance discrete mass, with diffuse replacement of the splenic architec of definitive surgical treatment, a radical neck dissection. The ture; (b) miliary type, in which there are fine nodules distributed patient was living 8.5 years later. uniformly throughout the parenchyma of the spleen (the follicu- SLAUGHTER(29). In Slaughter's original report of 1958 (31), lar distribution throughout the organ corresponds with the gross 11 of 18 patients having radical neck dissections survived for miliary appearance, e.g., Hodgkin's disease with nodular sclero-

TABLE 4 UNIFOCALHODGKIN'SDISEASE:SURGICALTREATMENTWITHELECTIVE POSTOPERATIVERADIATIONTHERAPY

ProcedureRadical of patients3 X-ray(r)3000-3000

neck dissection N.E.D.Â»(10, 12yr.); 1 dead 3 yr. 6 mo. Radical axillary dissection 3 3000-31)00 2 N.E.D. (10, 11 yr.); 1 dead 2 yr. 8 mo. RadicaldissectionSegmentai groin 51Postoperative3()00-3(i(X)3400Follow-up242mo.Dead N.E.D. (7,10,11, 11.5yr.); 1 dead 3 yr.

excision of lungNo. 2 yr. 6 mo. ' N.E.D., no evidence of disease; no further definitive treatment has been necessary.

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TABLE 5 joined removal of the hilar lymph nodes. The surgical exposure HODGKIN'SDISEASE:SURVIVALOF316 PATIENTS permits a concomitant biopsy of the liver, which may expose FROMDATEOF HISTOLOGICDIAGNOSIS unsuspected involvement. Most critical judgment must be exer cised in advocating splenectomy for patients with systemic Hodgkin's disease, because of the unusual hazards and the weight

orPATIENTS7418854316TREATMENT12 yr..â€ž of cumulative evidence that the operation does not measurably STAGEIIIIIITotalNo. alter the inexorable course of the disease. Strawitz et al. (34) yr.(%)83.378.464.931.462.35yr.(%)66.664.943.618.544.310 .Â°58.312.98.55.510.7No.ofpatients7816334have asserted that patients with Hodgkin's disease and leukemia exhibited a shorter survival time and higher operative mortality and morbidity after splenectomy than those patients with lym- Surgery+ X-ray02 phosarcoma and myeloid metaplasia. The prognosis following X-rayX-rayX-raySURVIVAL3 splenectomy for Hodgkin's disease is said to be much worse than for lymphocytic lymphosarcoma or for reticulum cell sarcoma.

Secondary Hypersplenism Numerous therapists have agreed that splenectomy is a valu able accessory measure to medical treatment of secondary hypersplenism associated with Hodgkin's disease. The intended TABLE 6 HODGKIN'SDISEASE:SURVIVALOF316 PATIENTS surgical patient should be critically evaluated and selected with FROMTIME OF 1st VISIT TO care. The overactivity of the spleen in hypersplenism creates an PACKMEDICALGROUP abnormal hÃ©matologiestate which requires immediate correction. The mechanism of secondary hypersplenism has been illusory, but the explanation of Doan (10) appears logical, namely, of sequestration and phagocytosis of blood cells and platelets by OFPATIENTS7418854316TREATMENT12 yr.(Â°7 STAGEIIIIIITotalNo. the spleen. Duckett (11) asserts that an autoimmunologic factor yr.(%)83.372.959.526.058.25yr.(%)66.637.524.614.826.910 1Â°58.39.76.43.68.4No.ofpatients7612227is apparent in many patients. According to Williams et al. (38), the bone marrow picture associated with secondary hypersple nism reveals the following alterations: megakarocytic hyper- Surgery+ X-ray62 plasia if there is peripheral thrombocytopenia; erythroid hyper- X-rayX-rayX-raySURVIVAL3 plasia in the presence of secondary hemolytic anemia; myeloid hyperplasia associated with peripheral neutropenia; or marrow hyperplasia affecting all cellular components if there exists a peripheral pancytopenia. It would be a truism to declare that the cellular marrow should be proved adequate before ventur ing to perform splenectomy in these patients, although Grace and colleagues (34) have successfully performed splenectomy in sis); (c) multiple discrete masses or conglomerations of smaller the presence of hypoplastic marrow. It is rational, therefore, to masses; (d) a huge, solitary, circumscribed mass. state that patients with Hodgkin's disease that is not accelerat ing, whose life is in danger from cytopenia and/or hemolysis Primary Hodgkiris Disease in the Spleen and who are recalcitrant to steroid therapy, should accept sple In the rare instance of primary Hodgkin's disease in the spleen, nectomy as a necessary surgical expedient. without studies suggesting the nature of the ailment such as blood Results of Splenectomy for Secondary Hypersplenism Associated count deviations, bone marrow changes, absence of suspicious with Hodgkin's Disease peripheral lymph node enlargement, the removal of the spleen may be done as an organ biopsy. Needle aspiration of the spleen Two parenthetic remarks should preface the summary of the is not often diagnostic. If the patient does not have generalized end results of treatment: (a) The surgical procedure of splenec Hodgkin's disease, there could be little objection to splenectomy tomy apparently does not accelerate the course of Hodgkin's as an initial measure. If splenomegaly is caused by visceral disease; (6) Splenectomy for secondary hypersplenism probably Hodgkin's disease which is systemic in distribution, sentiment does not change the eventual outcomeâ€”namely, fatalityâ€”for based on past experience is strongly against splenectomy and patients with Hodgkin's disease. preference is properly given to conventional irradiation and WILLIAMSETAL. (38). In a survey of some 400 patients with chemotherapy. There are circumstances, however, which compel Hodgkin's disease seen at the Ohio State University School of the therapist seriously to consider splenectomy in certain patients Medicine between 1940 and 1950, the most frequently occurring with generalized Hodgkin's disease. An example is a massive complication requiring surgical intervention was hypersplenism, splenic infarction with attendant pain and other acute symptoms. for which splenectomy was performed in 11 instances. Nine of Another example is a spleen which remains large and provocative these patients showed the hÃ©matologiere-equilibration that was of discomfort subsequent to proper antecedent irradiation and anticipated and predicted on the assumption that the spleen was chemotherapy. The extirpation of the spleen entails also a con the organ principally responsible for the cytopenic mecha-

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Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1966 American Association for Cancer Research. Surgical Treatment nism (10). No contraindications to splenectomy for hypersple gastrointestinal tract results from invasion via retroperitoneal nism were experienced in this series. The patients survived from or mesenteric nodes. Generally speaking, when the stomach is 1 to 28 months following removal of the spleen. involved, it is found in the terminal phase of the disease or at SCHULTZETAL. (26). Of 10 patients undergoing splenectomy necropsy. The Gastric Service at Memorial Hospital has not ob for hypersplenism, the postoperative survival was from 2 weeks served primary Hodgkin's disease of the stomach so diagnosed by to 25 months. the pathologists of that institution. Portmann et cd. (23) found WTKAWITZETAL. (34). Eighty % of the patients having sple 46 such cases and added 6 of their own for a total of 52. Warren nectomy for secondary hypersplenism in this series revealed a and Littlefield (37) as well as Marshall (21), all from the Lahey favorable hÃ©matologieresponse.The operative mortality was 8%. Clinic, reported 9 instances of primary Hodgkin's disease of the DUCKETT (11). Of 5 patients with Hodgkin's disease and stomach. hypersplenism who had splenectomy, 4 lived from 2 to 3.5 years Atlee (3) performed a gastrectomy for priman- Hodgkin's dis and 1 died in 2 months but not until platelets increased from ease; the patient was living and well 7 years later. Our report in 50,000 to 600,000 during the 1st postoperative week. cludes only 2 subtotal gastrectomies, both performed for intrac ROUSSELOTETAL.(25). Of 347 patients with Hodgkin's disease, table gastric hemorrhage in stomachs secondarily involved by 14 (4f;Â¿)required splenectomy. The operative mortality was 7%. Hodgkin's disease: 1 patient survived 17 months, the other for Two patients survived for 7.5 and 11.5 years, respectively. The 4.5 years (Table 7). Contrast the results with primary lympho- postoperative survival time of 12 patients was 5.9 months. sarcoma of the stomach, of which there were 9 cases among 567 patients (22), with several long-term cures following total gas Gastrointestinal and Retroperitoneal Involvement trectomy. Graver and Herrmann (8) have stated that survival from the immediate effects of gastrointestinal surgen- confers as Abdominal involvement was the initial manifestation of Hodgkin's disease in 26 patients (11.4%) in our present series. much as twice the usual life expectancy on the treated patient. Other authorities assert that surgical therapy offers no better If laparotomy for biopsy is done, the surgeon, by the exercise of results than proper irradiation. It has been said, without ade judgment and technical skill, may remove the bulk or all of the quate proof, that extirpation of a major focus of this disease tumor, possibly relieving distressing symptoms and affording palliation. The periphery of the tumor-bearing region is marked affords temporary growth restraint on the residual disease. SMALLINTESTINE.Primary Hodgkin's disease of the small in by silver clips, followed postoperatively by an adequate dose of irradiation. testine occurred in 2 instances in the present series; the more LIVER. At the time of death, the liver may be implicated in common secondary involvement occurred in 6 patients. In 50-60 9Â¿ofpatients (15). Primary hepatic Hodgkin's disease has testinal obstruction, partial or complete, is the signal of involve been reported (35) but is indeed rare. We have not encountered ment; children may have intussusception. Of 6 of our patients it once in our 316 patients. Not one of the 60 hepatic lobectomies having laparotomy for intestinal obstruction, 2 were inoperable, we have performed has been for primary Hodgkin's disease. 2 had bypass enteroenterostomy (surviving for 7 and 10 months), STOMACH.During the years 1932-55, postmortem examina and 2 had resection and anastomosis (surviving for 6 and 16 tions were performed on 217 patients with Hodgkin's disease at months). Memorial Hospital, and in 29 (13.4%) the stomach was involved. COLON.Priman- Hodgkin's disease of the colon occurred in Gastric localization as a part of generalized Hodgkin's disease is no patient in this series; secondary involvement was found in 9 not rare, but the disease in a few instances has been limited to the instances. Three patients had lesions within the reach of the gastrointestinal tract (4, 28). Usually the involvement of the sigmoidoscope. Complications included obstruction, perforation,

TABLE 7 PALLIATIVESURGICALPROCEDURESIN12 PATIENTSWITHHODGKIN'SDISEASE

StageIIIIIIIIIKo. ofpatients26112IndicationGastric life4.5 of

hemorrhageSmall gastrectomyResection yr.; 17mo.6

intestinal and anastomosis, mo.; Hi mo. obstructionIntestinal 2 patients Bypass enteroenterostomy, 7 mo.; 10 mo. 2 patients patientsHemicolectomySplenectomyKemovalInoperable, 2 4 mo.; 6mo.4

obstructionHemolytic yr. 1(1mo.4

anemiaBulky mo.7

retroperitoneal of bulky massDuration mo.; 2 yr. Hodgkin's diseaseProcedureSubtotal

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TABLE 8 space is fibrotic and unusually radioresistant. Under these and THORACICINVOLVEMENTINHODGKIN'SDISEASE certain other circumstances, laminectomy is feasible for quick de compression. Laminectomy is also indicated whenever there is INVOLVEMENTNo bony compression of the spinal cord secondary to vertebral frac ture due to osteolytic Hodgkin's disease. Graver (7) has cited an .ofpatients17521%5.416.4SECONDARYINVOLVEMENTNo.ofpatients5711186%18.035.127.2instance in which the surgical removal of a bulky protruding mass invading both plates of the skull, with pressure on the brain, PleuritieffusionMediastinalLung, was definitely of palliative value.

parenchymalINITIAL Involvement of Bone An extremely high percentage of patients with Hodgkin's dis and hemorrhage. One patient had a hemiooleetomy for Hodgkin's ease ultimately have foci in the red marrow of the vertebrae, ribs, disease causing obstruction at the splenic flexure; survival was pelvis, skull, and femurs. Kooreman and Haex (17) have re for 4 years and 10 months. ported primary disease of the skeleton, but surgical therapy for bone lesions other than rare pathologic fractures is seldom em Intrathoracic Involvement ployed. In our series, almost 1 in 6 patients had initial intrathoracic Hodgkin's disease. Fifty-two patients (16.49o) had mediastinal Involvement of Other Viscera adenopathy; 12 (23f;Â¿)had associated pleural effusion. Five pa Primary Hodgkin's disease has been reported as originating in tients had pleural effusion without detectable mediastinal in the kidney, the uterus, and the ovary, but nephrectomy and pan- volvement. One patient had a solitary nodular intrapulmonic hysterectomy are seldom applicable. Primary Hodgkin's dis lesion which proved to be Hodgkin's disease on segmental ex ease of the breast is rare; radical mastectomy for secondary cision. Primary pulmonary Hodgkin's disease has been reported mammary involvement is not done. by Charr and Wascolonis (5), VersÃ©(36),and Simonds (27). The mediastinal nodes are commonly involved, especially during Conclusions childhood. It can be readily appreciated that surgical therapy rarely is indicated under these circumstances. Graver relates an 1. The clinical settings in Hodgkin's disease in which a surgical instance of upper right pulmonary lobectomy for repeated and approach may be the initial treatment of choice are enumerated. worsening hemoptysis arising from an eroded bronchus. Lung 2. A plea is made for the earlier diagnosis of unifocal Hodgkin's abscesses are not infrequent and present a special problem. disease in the hope that this may allow a higher salvage rate and In patients who have been on long-term steroid therapy, potential cure in this limited group of patients. nocanlial abscesses sometimes occur. Aspiration of these cavities, 3. The general principles and indications for the initial treat or even thoracotomy with adequate biopsy, culture, and drain ment of patients with unifocal Hodgkin's disease by surgen* are age, may be necessary. The only surgical procedure done with discussed. A full tumor dose of irradiation is, nevertheless, given some frequency is the minor expedient of pleurocentesis when to any patient who undergoes wide dissection for unifocal Hodg indicated, although this procedure also offers an avenue for the kin's disease. intrapleural introduction of chemotherapeutic agents or radio 4. The 10-year survival rate of a limited number of Stage I active ceramic microspheres (Table 8). patients treated initially with surgery and irradiation at the Pack Medical Group seems to indicate that an initial radical surgical Involvement of the Central Nervous System approach followed by an adequate dose of irradiation (3000- Prevertebral Hodgkin's disease may invade between the verte 3600 r) offers these patients a better chance for long-term sur vival and potential cure than irradiation alone. The 10-year sur brae to reach the epidural space, producing a dumbbell tumor vival rate of patients thus treated was significantly higher than effect. With rapid growth, paraplegia may result, thus creating that of patients with Stage I disease that was amenable only to an acute emergency. The pressure on the spinal cord must be irradiation. relieved immediately; else the paralysis may be permanent. Two 5. Palliative surgical procedures, employing accepted surgical methods of procedure have their stout advocates and both are criteria, are at times necessary, and prolonged survival of some probably right. One school of thought immediately administers a patients has been noted. large dose of nitrogen mustard or vinblastine followed as soon as 6. Surgery as the initial treatment of choice in early Hodgkin's possible, day or night, by the 1st exposure to external irradiation. disease, followed by irradiation in adequate dosage, should be re- Complete relief from the compression symptoms and signs of evaluated. myelitis has been secured many times by external irradiation alone (33). One of our patients obtained complete remission and has been in good health for 4 posttreatment years. Radiation ther References apy in Â¡adequatedosage may induce edema of tissue within an en 1. Ahmann, D. L., Kiely, J. M., Harrison, E. G., and Payne, closed space, which could aggravate the cord compression. This W. S. Splenic Lymphoma: A Study of 49 Cases in Which the contingency seldom occurs unless previous radiation therapy has Diagnosis Was Made at Splenectomy. Cancer, 19: 461-69,1966. been given, or the focus of Hodgkin's disease in the epidural 2. Ariel, I. M., and Resnick, M. I. The Intralymphatic Admin-

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istration of Radioactive Isotopes and Cancer Chemotherapeu- tions of Hodgkin's Disease of (he Gastrointestinal Tract. Am. tic Drugs. Surgery, 55: 355-63, 1964. J. Roentgenol., 78: 772-87, 1954. 3. Atlee, J. L., Jr., Rowan, P. J., and /iegler, E. E. Hodgkin's 24. Rosenberg, S. A., Diamond, H. D., Jaslowitz, B., and Craver, Disease of the Stomach with Free Perforation and Apparent L. F. Lymphosarcoma. A Review of 1,269 Cases. Medicine, Surgical Cure. Ann. Surg., 134: 1052-57, 1951. 40: 31-84, 1961. 4. Avent, C. H. Primary Isolated Lymphogranulomatosis (Hodg 25. Rousselot, L. M., Relia, A. J., and Rot t ino, A. Splenectomy kin's Disease) of the Stomach. Report of a Case. Arch. Surg., for Hypersplenism in Hodgkin's Disease. A Reappraisal. Am. 39: 423-28, 1939. J. Surg., 103: 769-74, 1962. 5. Charr, R., and Wascolonis, A. Pulmonary Lesions in Hodg 26. Schultz, J. C., Denny, W. F., and Ross, S. W. Splenectomy in kin's Disease. J. Am. Med. Assoc., 116: 2013-14, 1931. Leukemia and Lymphoma. Report of Twenty-Four Cases. 6. Graver, L. F. Hodgkin's Disease. In: F. Tice (ed.), Practice Am. J. Med. Sci., $47: 30-36, 1964. of Medicine, Vol. 5, pp. 107-52. Hagerstown, Md.: W. F. 27. Simonds, J. P. Review of Hodgkin's Disease. Arch. Pathol., Prior Co., 1951. / : 394-430, 1926. 7. â€” â€”. Treatment of Hodgkin's Disease. In: G. T. Pack and 28. Singer, H. A. Primary Isolated Lymphogranulomatosis of the I. M. Ariel (eds.), Treatment of Cancer and Allied Diseases, Stomach. Arch. Surg., 22: 1001-17, 1931. Ed. 2, Vol. 9, pp. 168-91. New York: Hoeber Medical Divi 29. Slaughter, D. P. Radical Surgery. In: P. Rubin (ed.), Sympo sion, Harper & Row, 19(V4. sium on Hodgkin's Disease: Curability of Localized Hodgkin's 8. Graver, L. F., and Herrmann, J. lÃ¬.Abdominal Lympho Disease by Surgery, Radiotherapy, and Chemotherapy. J. Am. granulomatosis. Am. J. Roentgenol., 55: 1(55-72, 1946. Med. Assoc., 191: 25-32, 1965. 9. Diamond, H. J). The Medical Management of Cancer. New 30. Slaughter, D. P., and Craver, L. F. Ilodgkin's Disease; 5- York: GruÃ±e& Stratton, 1958. Year Survival Rate; Value of Early Surgical Treatment; 10. Doan, C. A. Hypersplenism. Bull. N. Y. Acad. Med., Ã•B: Notes on 4 Cases of Long Duration. Am. J. Roentgenol., 47: 625-50, 1949. 596-606, 1942. 11. Duckett, J. W. Splenectomy in the Treatment of Secondary 31. Slaughter, D. P., Economou, S. G., and Southwick, S. W. Hypersplenism. Ann. Surg., 157: 737-46, 1963. Surgical Management of Hodgkin's Disease. Ann. Surg., 148: 12. Gall, E. A. The Surgical Treatment of Malignant Lymphoma. 705-9,1958. Ibid., 118: 1064-70, 1943. 32. Smith, D. F., and Klopp, C. T. The Value of Surgical Re 13. Gall, E. A., and Mallory, T. B. Malignant Lymphoma; Clini- moval of Localized Lymphomas. Surgery, 49: 469-76, 1961. copathologic Survey of 613 Cases. Am. J. Pathol., 18: 381-429, 33. Smith, M. J., and Stenstrom, K. W. Compression of Spinal 1942. Cord Caused by Hodgkin's Disease. Radiology, 51: 77-84, 14. Hodgkin, T. On Some Morbid Appearances of the Absorbent 1948. Glands and Spleen. Med. -Chir. Trans., 17: 68-114, 1832. 34. Strawitz, J. G., Sokal, J. E., Grace, J. T., Jr., Mukhtar, F., 15. Hoster, H. A., Dratman, M. B., Craver, L. F., and Rolnick, and Moore, G. E. Surgical Aspects of Hypersplenism in H. A. Hodgkin's Disease. Cancer Res., 8:1-48, 49-78,1948. Lymphoma and Leukemia. Surg. Gynecol. Obstet., 112: 89-95, 16. Jackson, H., Jr., and Parker, F., Jr. Hodgkin's Disease and 1961. Allied Disorders. New York: Oxford University Press, 1947. 35. Symmers, D. Clinical Significance of the Deeper Anatomic 17. Kooreman, P. J., and Haex, A. J. C. Hodgkin's Disease of the Changes in Lymphoid Disease. Arch. Internal. Med., 74: 163- Skeleton. Acta Med. Scand., Ilo: 177-96, 1943. 18. Lacher, M. J. Role of Surgery in Hodgkin's Disease. New 71, 1944. 36. VersÃ©,M. Die Lymphogramilomutose der Lunge und der Engl. J. Med., e68: 289-92, 19(0. Brustfells. In: Henke and Lubarsch (eds.), Handbuch der 19. Lukes, R. J. Relationship of Histologie Features to Clinical Stages in Hodgkin's Disease. Am. J. Roentgenol., 90: 944-55, Speziellen Pathologischen Anatomie und Histologie, Part 3, pp. 280-343. Berlin: Julius Springer, 1931. 1963. 37. Warren, K. W., and Littlefield, J. B. Malignant Lymphoma of 20. Malpighi, M. De Viscerum Structura. Bonni Opera Omnia, the Gastrointestinal Tract. Surg. Clin. North Am., 35: 735-46, 2: 111, 1666. 21. Marshall, S. F. Gastric Tumors Other Than Carcinoma; 1955. Report of Unusual Cases. Surg. Clin. North Am., 36: 693- 38. Williams, R. D., Andrews, N. C., and X.anes, R. P., Jr. Major Surgery in Hodgkin's Disease. Surg. Gynecol. Obstet., 93: 702, 1955. 22. Molander, D. W., and Pack, (!. T. Lymphosarcoma: Choice 036-40, 1951. of Treatment and End Results in 567 Patients. Rev. Surg., 39. Wroblewski, Â¥.,Pack, G. T., and LaDue, J. S. Indications for 20: 3-31, 1963. Exploratory Laparotomy in Obscure Chronic Abdominal 23. Portmann, U. V., Dunne, E. F., and Hazard, J. B. Manifesta Disease. N. Y. State J. Med., 54: 2073-77, 1954.

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FIG. 1. Lymphangiographic diagnosis. .1, Bilateral involvement of the iliac lymph nodes. R, Demonstration of Hodgkin's disease in the abdominal and iliac lymph nodes after lymphatic infusion of Ethiodol-131!.

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FIG. 2. Radical groin dissection for Hodgkin's disease. Dissection of femoral, inguinal, iliac, and obdurator lymph nodes. Eight-year freedom from evidence of Hodgkin's disease.

JUNE 1966 1263

George T. Pack and David W. Molander

Cancer Res 1966;26:1254-1263.

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