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Staging laparotomy in Hodgkin's lymphoma: 1979 to 1988
Staging Laparotomy in Hodgkin’s Lymphoma: 1979 to 1988 Peter C. Muskat, Maj, USAF, MC, Robert A. Johnson, Maj, USAF, Gary J. Bowers, Maj, USAF, MC, LacklandAir Force Base, Texas
A retrospective review of patients with Hodglcin’s lymphoma undergoing staging laparotomy was done. Ninety-four patients were identified for analysis. Preoperative lymphangiography was performed in 86 patients, and computed tomography of the abdomen was performed in 53. Both proved to have an accuracy rate of 76%. Mortality and 30day morbidity rates were 0% and 17%, respectively, when both major (8%) and minor (10%) complications were considered. Late complications (greater than 30 days) were noted in 5%. The results of the hqmrotomy required a change in staging in 28% of patients, with alterations in subsequent clinical management occurring in 18%. In selected patients, staging laparotomy is safe and remains a reliable means of determining the intra-abdominal extent of Hodgkin’s lymphoma.
MC,
he introduction of megavoltage radiotherapy and T lymphangiography led to the treatment of infradiaphragmatic Hodgkin’s lymphoma with radiation, Unfortunately, radiation hepatitis frequently resulted when the liver was irradiated [I]. Given the unreliability of clinical staging of the abdomen and the potential consequences of radiotherapy, the usefulness of staging laparotomy for more precise definition of the &a-abdominal sites of Hodgkin’s disease was advocated [2]. As such, only those patients with documented disease would be subjected to the risks of therapy. Subsequently, staging laparotomy was shown to alter not only the final staging determination but also the resulting choice of therapy [2]. The past 25 years have seen improvements in radio therapy techniques and refmements in chemotherapy that have resulted in improved survival and longer disease-free intervals in patients with Hodgkin’s lymphoma [3]. Concomitantly, an increased understanding of the short-term and long-term risks associated with these therapies has developed. As a result, efforts have been made to improve the efficacy of clinical staging so as to avoid the necessity of laparotomy. Various imaging studies have been utilized; however, none reliably predicts intraabdominal disease, particularly in the spleen, liver, and upper abdominal lymph nodes [4]. Although patient selection criteria have become more selective, a significant number of patients with Hodgkin’s lymphoma continue to require staging laparotomy [5-71. Herein, we present a IO-year experience at Wilford Hall United States Aii Force Medical Center (WHMC) with staging laparotomy. The objectives of the study were to (1) evaluate the effectiveness of clinical staging, (2) assess the impact of laparotomy on the patient’s final stage and resulting therapy, (3) evaluate the safety of the procedure, and (4) identify any long-term sequelae resulting from the operation. PATIENTS AND METHODS
From the Departments of Surgery, Section Surgical Oncolojgy(PCM, GJBk and Hematolotzv/Medical Oncolom (RAJk Wiiord Hall USi6 Medical Center~ickland Air Fom-bak, Tekis. Request for reprints should be addmsed to Gary J. Bowers, Maj, USAF, MC, Department of Surgery, Section Surgical Oncol~, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas, 78236-5300. The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the United States Air Force or the Department of Defense. Pmented at the 43rd Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24,199l.
THE AMERICAN
Using the WHMC Tumor Registry, a retrospective review of the records of patients with Hodgkin’s lymphoma was performed. Those patients undergoing staging laparotomy as part of their pretherapy evaluation during the years 1979 to 1988 were identified. In each of these patients, age, sex, site of initial disease presentation, and the histologic subtype of the disease were noted. The cliical stage of each patient and the means used for its determination were ascertained. The results of laparotomy and all surgery-related complications were determined. The pathologic stage was compared with the results of clinical staging. Patient records were reviewed to see how often the restaging influenced the selection of subsequent therapies. The accuracy rate and positive pre-
JOURNAL
OF SURGERY
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162
DECEMBER
1991
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MUSKATET AL
phocyte-depleted subtypes were uncommon (4% and 1%, respectively). A thorough history, physical examination, and chest roentgenogram were obtained in all patients. Mediastinal disease was evident in 53% of the roentgenograms. LymNo. of Staging No. of Year Patients* Laparotomies (%)+ phangiography was performed in 86 patients (92%); 19 were interpreted as positive, revealing either lymph 1979 IO (44) 23 node(s) enlargement, architectural defects, displacement 1980 22 14 (64) 1981 27 14 (52) of the nodes, and/or a persistent channel phase. In 58 1982 13 (81) 16 patients (67%), the lymphangiogram was read as normal, 1983 16 6 (50) and, in nine others (11%) the findings were equivocal. 1984 6 5 (63) With the advent of computed tomography (CT), abdomi1985 12 5 (42) 1986 17 nal scans became an integral component of clinical stag4 (24) 1987 30 9 (30) ing. In 53 patients (57%), primarily those in the later years of this review, abdominal CT scans were obtained. The scan was interpreted as normal in 41 patients (77%), *Patients with newly diagnosed Hodgkin’s lymphoma for represented year. abnormal in 8 (15%), and equivocal in 4 (8%). Based on tNum!xr of patients/year newly diagnosed with Hodgkin’s lymphoma undergothe preoperative evaluation, 94 patients were clinically ing staging laparotomy. staged as follows: 27 Stage I (A/B), 37 Stage IIA, 15 Stage IIB, 7 Stage IIIA, 4 Stage IIIB, 1 Stage TVA,and 3 Stage IVB (Figure 1). I Surgical staging was accomplished by multiple resiPathologic Stage dent surgeons with staff supervision. Laparotomy was Total 2A 28 3A 38 4A 40 1 performed through a midline incision. Multiple liver biopsies, splenectomy, and nodal sampling of the celiac, 37 Clinical portal, periaortic, splenic, mesenteric, and iliac nodes Stage were performed. All specimens were submitted fresh to pathology. Subsequent histopathologic reports revealed 19 patients with positive lymph nodes and 25 patients with intrasplenic involvement, 7 of whom also had hepatic involvement. Fourteen patients had a combination of nodal and splenic disease. Based on these findings, 20 23 34 10 10 8 2 7 94 patients were upstaged relative to their clinical evaluaFlgura 1. Clinicaland pathologicstagingof all patientsundergoing tion, and six were downstaged, for a total stage change rate of 28% (Figure 1). staginglaparotomyfcf Hodgkin’s@nphoma. Lymphangiography was found to accurately predict intra-abdominal disease in 76% of the patients with a dictive value of both preoperative lymphangiography and positive predictive value of 55%. Abdominal CT was similarly accurate (76%) with a positive predictive value of computed tomography were calculated 181. 60%. Therapy was initiated in 100% of patients who underRESULTS Of 193 newly diagnosed patients with Hodgkin’s lym- went laparotomy. In 17 patients (18%), the subsequent therapy employed was different than that which would phoma identified during the study period, 97 underwent staging laparotomy. Three patients were excluded in have been employed based on clinical staging alone. whom the diagnosis was unknown preoperatively, resultThere were no operative deaths. Thirty-day postopering in a total of 94 patients who were analyzed (Table I). ative complications were noted in 16 patients (17%). MaThere were 62 males and 32 females (ratio 1.9:1) with a jor complications occurred in 8%, including 4 major inmean age of 25 years (median: 27 years). The most com- fections (a fasciitis with wound dehiscence, a subfascial mon site of disease on initial evaluation was cervical ad- abscess, a subphrenic abscess, and a lobar pneumonia) enopathy (72%) with a left predominance noted. Other and 2 hemorrhagic complications. Minor complications locations of abnormal nodal enlargement included the were reported in 9 patients (IO%), including 2 urinary mediastinum (13%), axilla (7%), inguinal region (7%) tract infections, 1 superficial wound infection, and 1 case and other nodal sites (1%). Twenty-five patients (26%) of transient femoral neuropathy. Blood transfusions were had B-type systemic symptoms. required in two patients. All patients had a biopsy-proven diagnosis prior to Late complications, defined as those occurring more staging laparotomy. The disease was categorized accord- than 30 days after surgery but related to the procedure, ing to the Ann Arbor classification [9]. Nodular scleros- were noted in live patients (5%). An incisional hernia was ing (7 1%) and mixed cellularity (24%) were the most repaired in one patient. Three patients were hospitalized frequent subtypes. Lymphocyte-predominant and lym- for partial small bowel obstruction, but none required TABLE I Patients with Hodgkln’s Lymphoma Undergoing Staging Laparotomy for Years 1979 to 1988
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surgical intervention. In one patient, an episode of pneumococcal sepsis was documented.
COMMENTS Surgery’s role in the management of Hodgkin’s lymphoma is solely diagnostic, serving only to define the exact stage of the disease. At present, the treatment of Hodgkin’s lymphoma consists of external beam radiotherapy, multiple drug chemotherapy, or a combination of both. As the choice of therapy is very much predicated upon the extent of disease, precise staging is of great importance. As in our series, most patients present with supradiaphragmatic nodal involvement [ 1I -I 51. Thus, it is the presence or absence of intra-abdominal disease and its extent that must be discerned prior to initiating therapy. Because of the inadequacy of clinical staging of the abdo men, Glatstein et al [2] in 1969 introduced the concept of staging laparotomy. This procedure, by proviclmg a precise definition of intra-abdominal disease, allows for the tailoring of subsequent therapy to the extent of patholo gY* Clinical staging of the abdomen relies heavily on various radiographic studies. Lymphangiography has been used extensively but with a less than ideal accuracy rates and positive predictive values as observed in our patients and by others [4,16]. The lymphangiogram is not very reliable above the level of the renal vessels nor does it assess the liver or spleen. Extension of the disease into the upper abdomen from supradiaphragmatic disease can frequently go undiagnosed by lymphangiography. Computed tomography also often poorly defines upper abdominal nodal pathology. Hence, CT has not signiticantly altered the efficacy of clinical staging as evidenced herein and by others [I7’J. Thus, clinical staging of the abdomen still remains imprecise in a significant number of patients. In our series, 28% were m&aged. This rate concurs with that reported by others (Table II). This discrepancy has clinical importance as 18% of our patients received different therapy based on the results of the staging laparotomy. Both radiation and chemotherapy have inherent risks that must be considered when recommendmg one or the other modality, another reason for precise staging. Radiotherapy employs either total or subtotal lymphoid irradiation, which may or may not be extended to include the liver. Typically, doses range from 35 to 44 Gy [181. Complications may include pneumonitis, esophagitis, enteritis, and hepatitis [ 191. Additionally, a considerable portion of the bone marrow is irradiated within these fields, especially if total lymphoid irradiation techniques are employed. This may have significant implications if these patients subsequently require salvage chemotherapy for recurrent disease. Multiple chemotherapeutic regimens are currently employed in the management of Hodgkin’s lymphoma. Patients with stage IV disease and a large number of those with stage III are candidates for chemotherapy. Two more commonly used regimens are MOPP (metho-
TABLE II Reported Series o?Patlents with Hodgkln’s Lymphoma Undergolng gtaglng Laparotomy JO-Day Hospital Author Year
1221 (231 (241 [I51 1251 [261
vu u21 (141 [731 VI
1973 1978 1979 1980 1981 1982 1982 1982 1984 1985 1980
No. of % Stage Patients Change 81 90 107 123 50 100 310 316 123 825 50
40 30 39 31 30 35 27 43 38
Operative Complications (%) Mortality (%) Major Minor 0.8 0 0 0 0 0 0.3 0 0 0.1 0
5 1% 5 4 13 IO 4 0 10 IO 6
19 14 8 9 31 5 0
trexate, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazinc) [20]. The risks associated with chemotherapy are considerable, including infection, azoospermia, infertility, myocarditis, and an increased risk for a second neoplasm [a. The MOPP protocol has been associated with temporary or permanent sterility in 90% of males and amenorrhea in 50% of females [21]. The relative risk of a second cancer following MOPP therapy is five times that expected for the general population, with an actuarial risk of 13% for solid tumors at 15 years and a 3% risk of leukemia at 10 years [101. The risk of leukemia increases approximately ten-fold in patients who receive both irradiation and chemotherapy. Whereas the risk of leukemia peaks at approximately 10 years, the incidence of solid tumor increases steadily with time [101. Staging laparotomy does have inherent risks. Fortunately, operative mortality for the procedure is low, less than 1% in most series including ours (Table II). The 30day hospital morbidity in our series was 1796, with 8% major and 10% minor complications occmring. This also is similar to that reported in other series (Table II). Of particular interest to us and something not generally addressed in prior reports were the risks for late complications (i.e., those occurring 30 days after surgery but which were likely consequences of the surgery). In four of our patients, late problems were clearly associated with the laparotomy, only one of which was related to technical error (an incisional hernia). Three patients had problems with bowel obstruction secondary to adhesions. Another patient developed life-threatening pneumococcal sepsis, a problem that in part may have been related to the patient’s underlying disease, but which likely was aggravated by splenectomy. Including thii last individual, 5% of our patients experienced significant long-term sequelae as a consequence of the operative procedure. In recent years, there have been several subgroups of patients with Hodgkin’s lymphoma identified who appear to be at low risk for subdiaphragmatic disease and hence can be spared staging laparotomy [5-71. Reassessing the
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patients in our series using these newer criteria, 12 would no longer be considered for laparotomy. As predicted, none of these patients had a positive laparotomy. If we eliminate these 12 patients, clinical staging would have unreliably predicted disease in 32% of our patients. In summary we found, in accordance with others, that clinical staging at our institution was inadequate in a significant number of patients (28%). In 18% of these individuals, subsequent therapy was altered from that which would have been recommended based on clinical staging. The operation was safe but, in a few patients, did result in significant long-term adverse problems. Nonetheless, we would suggest that staging laparotomy continues to be a valuable and necessary tool in the staging of Hodgkin’s lymphoma in a select group of patients. REFERENCES 1. Kaplan HS. Evidence for a tumoricidal dose level in the radiotherapy of Hodgkin’s disease. Cancer Res 1966; 26: 1221-3. 2. Glatstein E, Guernsey JM, Rosenberg SA, et al. The value of laparotomy and splenectomy in the staging of Hodgkin’s disease. Cancer 1969; 24: 709-18. 3. Henry-Amar M, Somers R. Survival outcome after Hodgkin’s disease: a report from the International Data Base on Hodgkin’s disease. Semin Gncol 1990; 17: 758-68. 4. Castellino RA, Hoppe RT, Blank N, et al. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin’s disease.. AJR Am J Roentgen01 1984; 143: 37-41. 5. Johnson DW, Hoppe RT, Cox RS, et al. Hodgkin’s disease limited to intrathoracic sites. Cancer 1983; 52: 8-13. 6. Russel KJ, Hoppe RT, Colby TV, ef al. Lymphocyte predominant Hodgkin’s disease: clinical presentation and results of treatment. Radiother Oncol 1984; 1: 197-205. 7. Leibenhaut MH, Hoppe RT, Effon B, et al. Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin’s disease. J Clin Oncol 1989; 7: 81-91, 8. Mausner JS, Kramer S. Epidemiology-an introductory text. New York: WB Saunders Co, 1985: 217-23. 9. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tarbiana M. Report of the Committee on Hodgkin’s disease staging classification. Cancer Res 1971; 31: 1860-l. 10. Tucker MA, Coleman CN, Cox RS, et al. Risk of second cancer after treatment for Hodgkin’s disease. N Engl J Med 1988; 318: 76-81. Il. Glees JP, Barr LC, McElwain TJ, et al. The changing role of staging laparotomy in Hodgkin’s disease: a personal series of 310 patients. Br J Surg 1982; 69: 181-7. 12. Martin JK, Clark SC, Beart RW, et al. Staging laparotomy in Hodgkin’s disease: Mayo Clinic experience. Arch Surg 1982; 117: 586-91. 13. Taylor MA, Kaplan HS, Nelsen TS. Staging laparotomy with splenectomy for Hodgkin’s disease: the Stanford experience. World J Surg 1985; 9: 449-60. 14. Wobbes T, Lubbers EJC, Depauw BE. Results and complications of staging laparotomy in Hodgkin’s disease. J Surg Gncol 1984; 26: 135-7. 15. Sterchi JM, Myers RT. Staging laparotomy in Hodgkin’s disease. Ann Surg 1980; 191: 570-5. 16. Manstield CM, Fabian C, Jones S, et al. Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin’s disease. Cancer 1990; 66: 2295-9. 17. Magnusson A, Hagberg H, Hemmingsson A, et al. Computed
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tomography, ultrasound and lymphography in the diagnosis of malignant lymphoma. Acta Radio1 (Diagm) 1982; 23: 29-33. 18. Hoppe RT. Radiation therapy in the management of Hodgkin’s disease. Semin Oncol 1990; 17: 704-15. 19. Ingold J, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. AJR Am J Roentgen01 1964; 93: 20-4. 20. Long0 DL. The use of chemotherapy in the treatment of Hodgkin’s disease. Semin Gncol 1990; 17: 716-35. 21. Devita VT. The consequences of the chemotherapy of Hodgkin’s disease. Cancer 1981; 47: l-13. 22. Ferguson DJ, Allen LW, Ciriem ML, et al. Surgical experience with staging laparotomy in 125 patients with lymphoma. Arch Intern Med 1973; 131: 356-61. 23. Brogadir S, Fialk MA, Coleman M, et al. Surgical experiences with staging laparotomy in Hodgkin’s disease. Am J Med 1978; 64: 429-33. 24. Urlaub BJ, Mack E. Evaluation and complications of 107 staging laparotomies for Hodgkin’s disease. Ann Surg 1979; 190: 45-7. 25. Kaiser CW. Complications from staging laparotomy for Hodgkin’s disease. J Surg Oncol 1981; 16: 319-25. 26. Dent DM, King HS, Jacobs P. Is staging laparotomy necessary in Hodgkin’s disease? An analysis of 100 operations. S Afr Med J 1982; 62: 509-11. 27. Jones AR, Ruether JD, Ruether BA. Staging laparotomy in Hodgkin’s disease: a community hospital experience. J Surg Oncol 1988; 38: 217-20. DISCUSSION J. Ralph Broadwater
(Little Rock, AR): This is an important paper because it compares the results of the clinical staging of patients with Hodgkin’s disease with the findings of pathologic staging in order to: (1) identify the accuracy of radiologic staging, (2) examine how often therapy was changed by the surgical staging, and (3) identify the early and late morbidity of surgical staging. The authors mention that 96 patients with Hodgkin’s disease in this same time interval did not undergo staging laparotomy. Why were these patients not offered surgical staging? Many studies have indicated that the presence of B symptoms may indicate a high incidence of a positive staging laparotomy. Did you examine this in your study? Did you examine how often the spleen was positive in staging laparotomy? Have you examined hemisplenectomy or even the need to preserve the spleen in selected patients, and is there a role for laparoscopic staging in these patients? James A. Edney (Omaha, NE): At our institution, which has a very active lymphoma treatment group, the indications for staging laparotomy have fallen off precipitously in the last decade, from about 15 patients a year to less than one or two annually. Have the authors noted this same phenomenon? This appears to be the result of the efficacy of CT scanning, tine needle aspiration, and other diagnostic modalities in contributing to the accuracy of clinical staging. John A. Butler (Torrance, CA): If an abnormality is discovered on the basis of either the CT scan or the lymphangiogram, have the authors attempted using a CT guided needle aspiration to diagnose the presence of intra-abdominal disease? A negative cytology would not be of value, but a positive result would obviate the need for laparotomy.
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Peter C. Muskat (closing): Of the 96 patients that were not offered the procedure, they generally fell into a group in whom the hematology-oncology specialist felt confident about the results of clinical staging and proceeded on to therapy, either radiotherapy and/or chemotherapy. I would imagine a number of them were stage IV or stage I patients. For those patients with B-type symptoms, yes, there is an increased incidence of positive intra-abdominal disease. We had only 26 patients that had positive B-type symptoms. We had 25 spleens that showed invasion by Hodgkin’s disease in our positive laparotomy experience, and that was, by far, the most common location for intraabdominal disease. There have been several good
studies to suggest that hemisplenectomy is probably inadequate. Dr. Edney, we considered the number of patients per year during our study, and it was fairly constant. Early in our study, about 1980, we had 14 patients that underwent the procedure during that time. In 1988, we had 12 patients undergo staging laparotomy. The total number of patients with Hodgkin’s lymphoma that we have seen in our institution hasn’t significantly changed, and this may be a statistical anomaly. Dr. Butler, for the most part at our institution, our Pathology Department has not been successful in determining if Hodgkin’s disease is present on the basis of fine-needle aspirate of the lymph node.
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VOLUME 162 DECEMBER 199 1
607
A retrospective review of patients with Hodglcin’s lymphoma undergoing staging laparotomy was done. Ninety-four patients were identified for analysis. Preoperative lymphangiography was performed in 86 patients, and computed tomography of the abdomen was performed in 53. Both proved to have an accuracy rate of 76%. Mortality and 30day morbidity rates were 0% and 17%, respectively, when both major (8%) and minor (10%) complications were considered. Late complications (greater than 30 days) were noted in 5%. The results of the hqmrotomy required a change in staging in 28% of patients, with alterations in subsequent clinical management occurring in 18%. In selected patients, staging laparotomy is safe and remains a reliable means of determining the intra-abdominal extent of Hodgkin’s lymphoma.
MC,
he introduction of megavoltage radiotherapy and T lymphangiography led to the treatment of infradiaphragmatic Hodgkin’s lymphoma with radiation, Unfortunately, radiation hepatitis frequently resulted when the liver was irradiated [I]. Given the unreliability of clinical staging of the abdomen and the potential consequences of radiotherapy, the usefulness of staging laparotomy for more precise definition of the &a-abdominal sites of Hodgkin’s disease was advocated [2]. As such, only those patients with documented disease would be subjected to the risks of therapy. Subsequently, staging laparotomy was shown to alter not only the final staging determination but also the resulting choice of therapy [2]. The past 25 years have seen improvements in radio therapy techniques and refmements in chemotherapy that have resulted in improved survival and longer disease-free intervals in patients with Hodgkin’s lymphoma [3]. Concomitantly, an increased understanding of the short-term and long-term risks associated with these therapies has developed. As a result, efforts have been made to improve the efficacy of clinical staging so as to avoid the necessity of laparotomy. Various imaging studies have been utilized; however, none reliably predicts intraabdominal disease, particularly in the spleen, liver, and upper abdominal lymph nodes [4]. Although patient selection criteria have become more selective, a significant number of patients with Hodgkin’s lymphoma continue to require staging laparotomy [5-71. Herein, we present a IO-year experience at Wilford Hall United States Aii Force Medical Center (WHMC) with staging laparotomy. The objectives of the study were to (1) evaluate the effectiveness of clinical staging, (2) assess the impact of laparotomy on the patient’s final stage and resulting therapy, (3) evaluate the safety of the procedure, and (4) identify any long-term sequelae resulting from the operation. PATIENTS AND METHODS
From the Departments of Surgery, Section Surgical Oncolojgy(PCM, GJBk and Hematolotzv/Medical Oncolom (RAJk Wiiord Hall USi6 Medical Center~ickland Air Fom-bak, Tekis. Request for reprints should be addmsed to Gary J. Bowers, Maj, USAF, MC, Department of Surgery, Section Surgical Oncol~, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas, 78236-5300. The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the United States Air Force or the Department of Defense. Pmented at the 43rd Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24,199l.
THE AMERICAN
Using the WHMC Tumor Registry, a retrospective review of the records of patients with Hodgkin’s lymphoma was performed. Those patients undergoing staging laparotomy as part of their pretherapy evaluation during the years 1979 to 1988 were identified. In each of these patients, age, sex, site of initial disease presentation, and the histologic subtype of the disease were noted. The cliical stage of each patient and the means used for its determination were ascertained. The results of laparotomy and all surgery-related complications were determined. The pathologic stage was compared with the results of clinical staging. Patient records were reviewed to see how often the restaging influenced the selection of subsequent therapies. The accuracy rate and positive pre-
JOURNAL
OF SURGERY
VOLUME
162
DECEMBER
1991
603
MUSKATET AL
phocyte-depleted subtypes were uncommon (4% and 1%, respectively). A thorough history, physical examination, and chest roentgenogram were obtained in all patients. Mediastinal disease was evident in 53% of the roentgenograms. LymNo. of Staging No. of Year Patients* Laparotomies (%)+ phangiography was performed in 86 patients (92%); 19 were interpreted as positive, revealing either lymph 1979 IO (44) 23 node(s) enlargement, architectural defects, displacement 1980 22 14 (64) 1981 27 14 (52) of the nodes, and/or a persistent channel phase. In 58 1982 13 (81) 16 patients (67%), the lymphangiogram was read as normal, 1983 16 6 (50) and, in nine others (11%) the findings were equivocal. 1984 6 5 (63) With the advent of computed tomography (CT), abdomi1985 12 5 (42) 1986 17 nal scans became an integral component of clinical stag4 (24) 1987 30 9 (30) ing. In 53 patients (57%), primarily those in the later years of this review, abdominal CT scans were obtained. The scan was interpreted as normal in 41 patients (77%), *Patients with newly diagnosed Hodgkin’s lymphoma for represented year. abnormal in 8 (15%), and equivocal in 4 (8%). Based on tNum!xr of patients/year newly diagnosed with Hodgkin’s lymphoma undergothe preoperative evaluation, 94 patients were clinically ing staging laparotomy. staged as follows: 27 Stage I (A/B), 37 Stage IIA, 15 Stage IIB, 7 Stage IIIA, 4 Stage IIIB, 1 Stage TVA,and 3 Stage IVB (Figure 1). I Surgical staging was accomplished by multiple resiPathologic Stage dent surgeons with staff supervision. Laparotomy was Total 2A 28 3A 38 4A 40 1 performed through a midline incision. Multiple liver biopsies, splenectomy, and nodal sampling of the celiac, 37 Clinical portal, periaortic, splenic, mesenteric, and iliac nodes Stage were performed. All specimens were submitted fresh to pathology. Subsequent histopathologic reports revealed 19 patients with positive lymph nodes and 25 patients with intrasplenic involvement, 7 of whom also had hepatic involvement. Fourteen patients had a combination of nodal and splenic disease. Based on these findings, 20 23 34 10 10 8 2 7 94 patients were upstaged relative to their clinical evaluaFlgura 1. Clinicaland pathologicstagingof all patientsundergoing tion, and six were downstaged, for a total stage change rate of 28% (Figure 1). staginglaparotomyfcf Hodgkin’s@nphoma. Lymphangiography was found to accurately predict intra-abdominal disease in 76% of the patients with a dictive value of both preoperative lymphangiography and positive predictive value of 55%. Abdominal CT was similarly accurate (76%) with a positive predictive value of computed tomography were calculated 181. 60%. Therapy was initiated in 100% of patients who underRESULTS Of 193 newly diagnosed patients with Hodgkin’s lym- went laparotomy. In 17 patients (18%), the subsequent therapy employed was different than that which would phoma identified during the study period, 97 underwent staging laparotomy. Three patients were excluded in have been employed based on clinical staging alone. whom the diagnosis was unknown preoperatively, resultThere were no operative deaths. Thirty-day postopering in a total of 94 patients who were analyzed (Table I). ative complications were noted in 16 patients (17%). MaThere were 62 males and 32 females (ratio 1.9:1) with a jor complications occurred in 8%, including 4 major inmean age of 25 years (median: 27 years). The most com- fections (a fasciitis with wound dehiscence, a subfascial mon site of disease on initial evaluation was cervical ad- abscess, a subphrenic abscess, and a lobar pneumonia) enopathy (72%) with a left predominance noted. Other and 2 hemorrhagic complications. Minor complications locations of abnormal nodal enlargement included the were reported in 9 patients (IO%), including 2 urinary mediastinum (13%), axilla (7%), inguinal region (7%) tract infections, 1 superficial wound infection, and 1 case and other nodal sites (1%). Twenty-five patients (26%) of transient femoral neuropathy. Blood transfusions were had B-type systemic symptoms. required in two patients. All patients had a biopsy-proven diagnosis prior to Late complications, defined as those occurring more staging laparotomy. The disease was categorized accord- than 30 days after surgery but related to the procedure, ing to the Ann Arbor classification [9]. Nodular scleros- were noted in live patients (5%). An incisional hernia was ing (7 1%) and mixed cellularity (24%) were the most repaired in one patient. Three patients were hospitalized frequent subtypes. Lymphocyte-predominant and lym- for partial small bowel obstruction, but none required TABLE I Patients with Hodgkln’s Lymphoma Undergoing Staging Laparotomy for Years 1979 to 1988
604
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VOLUME 162 DECEMBER 1991
STAGINGLAPAROTOMY IN HODGKIN’S LYMPHOMA
surgical intervention. In one patient, an episode of pneumococcal sepsis was documented.
COMMENTS Surgery’s role in the management of Hodgkin’s lymphoma is solely diagnostic, serving only to define the exact stage of the disease. At present, the treatment of Hodgkin’s lymphoma consists of external beam radiotherapy, multiple drug chemotherapy, or a combination of both. As the choice of therapy is very much predicated upon the extent of disease, precise staging is of great importance. As in our series, most patients present with supradiaphragmatic nodal involvement [ 1I -I 51. Thus, it is the presence or absence of intra-abdominal disease and its extent that must be discerned prior to initiating therapy. Because of the inadequacy of clinical staging of the abdo men, Glatstein et al [2] in 1969 introduced the concept of staging laparotomy. This procedure, by proviclmg a precise definition of intra-abdominal disease, allows for the tailoring of subsequent therapy to the extent of patholo gY* Clinical staging of the abdomen relies heavily on various radiographic studies. Lymphangiography has been used extensively but with a less than ideal accuracy rates and positive predictive values as observed in our patients and by others [4,16]. The lymphangiogram is not very reliable above the level of the renal vessels nor does it assess the liver or spleen. Extension of the disease into the upper abdomen from supradiaphragmatic disease can frequently go undiagnosed by lymphangiography. Computed tomography also often poorly defines upper abdominal nodal pathology. Hence, CT has not signiticantly altered the efficacy of clinical staging as evidenced herein and by others [I7’J. Thus, clinical staging of the abdomen still remains imprecise in a significant number of patients. In our series, 28% were m&aged. This rate concurs with that reported by others (Table II). This discrepancy has clinical importance as 18% of our patients received different therapy based on the results of the staging laparotomy. Both radiation and chemotherapy have inherent risks that must be considered when recommendmg one or the other modality, another reason for precise staging. Radiotherapy employs either total or subtotal lymphoid irradiation, which may or may not be extended to include the liver. Typically, doses range from 35 to 44 Gy [181. Complications may include pneumonitis, esophagitis, enteritis, and hepatitis [ 191. Additionally, a considerable portion of the bone marrow is irradiated within these fields, especially if total lymphoid irradiation techniques are employed. This may have significant implications if these patients subsequently require salvage chemotherapy for recurrent disease. Multiple chemotherapeutic regimens are currently employed in the management of Hodgkin’s lymphoma. Patients with stage IV disease and a large number of those with stage III are candidates for chemotherapy. Two more commonly used regimens are MOPP (metho-
TABLE II Reported Series o?Patlents with Hodgkln’s Lymphoma Undergolng gtaglng Laparotomy JO-Day Hospital Author Year
1221 (231 (241 [I51 1251 [261
vu u21 (141 [731 VI
1973 1978 1979 1980 1981 1982 1982 1982 1984 1985 1980
No. of % Stage Patients Change 81 90 107 123 50 100 310 316 123 825 50
40 30 39 31 30 35 27 43 38
Operative Complications (%) Mortality (%) Major Minor 0.8 0 0 0 0 0 0.3 0 0 0.1 0
5 1% 5 4 13 IO 4 0 10 IO 6
19 14 8 9 31 5 0
trexate, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazinc) [20]. The risks associated with chemotherapy are considerable, including infection, azoospermia, infertility, myocarditis, and an increased risk for a second neoplasm [a. The MOPP protocol has been associated with temporary or permanent sterility in 90% of males and amenorrhea in 50% of females [21]. The relative risk of a second cancer following MOPP therapy is five times that expected for the general population, with an actuarial risk of 13% for solid tumors at 15 years and a 3% risk of leukemia at 10 years [101. The risk of leukemia increases approximately ten-fold in patients who receive both irradiation and chemotherapy. Whereas the risk of leukemia peaks at approximately 10 years, the incidence of solid tumor increases steadily with time [101. Staging laparotomy does have inherent risks. Fortunately, operative mortality for the procedure is low, less than 1% in most series including ours (Table II). The 30day hospital morbidity in our series was 1796, with 8% major and 10% minor complications occmring. This also is similar to that reported in other series (Table II). Of particular interest to us and something not generally addressed in prior reports were the risks for late complications (i.e., those occurring 30 days after surgery but which were likely consequences of the surgery). In four of our patients, late problems were clearly associated with the laparotomy, only one of which was related to technical error (an incisional hernia). Three patients had problems with bowel obstruction secondary to adhesions. Another patient developed life-threatening pneumococcal sepsis, a problem that in part may have been related to the patient’s underlying disease, but which likely was aggravated by splenectomy. Including thii last individual, 5% of our patients experienced significant long-term sequelae as a consequence of the operative procedure. In recent years, there have been several subgroups of patients with Hodgkin’s lymphoma identified who appear to be at low risk for subdiaphragmatic disease and hence can be spared staging laparotomy [5-71. Reassessing the
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patients in our series using these newer criteria, 12 would no longer be considered for laparotomy. As predicted, none of these patients had a positive laparotomy. If we eliminate these 12 patients, clinical staging would have unreliably predicted disease in 32% of our patients. In summary we found, in accordance with others, that clinical staging at our institution was inadequate in a significant number of patients (28%). In 18% of these individuals, subsequent therapy was altered from that which would have been recommended based on clinical staging. The operation was safe but, in a few patients, did result in significant long-term adverse problems. Nonetheless, we would suggest that staging laparotomy continues to be a valuable and necessary tool in the staging of Hodgkin’s lymphoma in a select group of patients. REFERENCES 1. Kaplan HS. Evidence for a tumoricidal dose level in the radiotherapy of Hodgkin’s disease. Cancer Res 1966; 26: 1221-3. 2. Glatstein E, Guernsey JM, Rosenberg SA, et al. The value of laparotomy and splenectomy in the staging of Hodgkin’s disease. Cancer 1969; 24: 709-18. 3. Henry-Amar M, Somers R. Survival outcome after Hodgkin’s disease: a report from the International Data Base on Hodgkin’s disease. Semin Gncol 1990; 17: 758-68. 4. Castellino RA, Hoppe RT, Blank N, et al. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin’s disease.. AJR Am J Roentgen01 1984; 143: 37-41. 5. Johnson DW, Hoppe RT, Cox RS, et al. Hodgkin’s disease limited to intrathoracic sites. Cancer 1983; 52: 8-13. 6. Russel KJ, Hoppe RT, Colby TV, ef al. Lymphocyte predominant Hodgkin’s disease: clinical presentation and results of treatment. Radiother Oncol 1984; 1: 197-205. 7. Leibenhaut MH, Hoppe RT, Effon B, et al. Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin’s disease. J Clin Oncol 1989; 7: 81-91, 8. Mausner JS, Kramer S. Epidemiology-an introductory text. New York: WB Saunders Co, 1985: 217-23. 9. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tarbiana M. Report of the Committee on Hodgkin’s disease staging classification. Cancer Res 1971; 31: 1860-l. 10. Tucker MA, Coleman CN, Cox RS, et al. Risk of second cancer after treatment for Hodgkin’s disease. N Engl J Med 1988; 318: 76-81. Il. Glees JP, Barr LC, McElwain TJ, et al. The changing role of staging laparotomy in Hodgkin’s disease: a personal series of 310 patients. Br J Surg 1982; 69: 181-7. 12. Martin JK, Clark SC, Beart RW, et al. Staging laparotomy in Hodgkin’s disease: Mayo Clinic experience. Arch Surg 1982; 117: 586-91. 13. Taylor MA, Kaplan HS, Nelsen TS. Staging laparotomy with splenectomy for Hodgkin’s disease: the Stanford experience. World J Surg 1985; 9: 449-60. 14. Wobbes T, Lubbers EJC, Depauw BE. Results and complications of staging laparotomy in Hodgkin’s disease. J Surg Gncol 1984; 26: 135-7. 15. Sterchi JM, Myers RT. Staging laparotomy in Hodgkin’s disease. Ann Surg 1980; 191: 570-5. 16. Manstield CM, Fabian C, Jones S, et al. Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin’s disease. Cancer 1990; 66: 2295-9. 17. Magnusson A, Hagberg H, Hemmingsson A, et al. Computed
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tomography, ultrasound and lymphography in the diagnosis of malignant lymphoma. Acta Radio1 (Diagm) 1982; 23: 29-33. 18. Hoppe RT. Radiation therapy in the management of Hodgkin’s disease. Semin Oncol 1990; 17: 704-15. 19. Ingold J, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. AJR Am J Roentgen01 1964; 93: 20-4. 20. Long0 DL. The use of chemotherapy in the treatment of Hodgkin’s disease. Semin Gncol 1990; 17: 716-35. 21. Devita VT. The consequences of the chemotherapy of Hodgkin’s disease. Cancer 1981; 47: l-13. 22. Ferguson DJ, Allen LW, Ciriem ML, et al. Surgical experience with staging laparotomy in 125 patients with lymphoma. Arch Intern Med 1973; 131: 356-61. 23. Brogadir S, Fialk MA, Coleman M, et al. Surgical experiences with staging laparotomy in Hodgkin’s disease. Am J Med 1978; 64: 429-33. 24. Urlaub BJ, Mack E. Evaluation and complications of 107 staging laparotomies for Hodgkin’s disease. Ann Surg 1979; 190: 45-7. 25. Kaiser CW. Complications from staging laparotomy for Hodgkin’s disease. J Surg Oncol 1981; 16: 319-25. 26. Dent DM, King HS, Jacobs P. Is staging laparotomy necessary in Hodgkin’s disease? An analysis of 100 operations. S Afr Med J 1982; 62: 509-11. 27. Jones AR, Ruether JD, Ruether BA. Staging laparotomy in Hodgkin’s disease: a community hospital experience. J Surg Oncol 1988; 38: 217-20. DISCUSSION J. Ralph Broadwater
(Little Rock, AR): This is an important paper because it compares the results of the clinical staging of patients with Hodgkin’s disease with the findings of pathologic staging in order to: (1) identify the accuracy of radiologic staging, (2) examine how often therapy was changed by the surgical staging, and (3) identify the early and late morbidity of surgical staging. The authors mention that 96 patients with Hodgkin’s disease in this same time interval did not undergo staging laparotomy. Why were these patients not offered surgical staging? Many studies have indicated that the presence of B symptoms may indicate a high incidence of a positive staging laparotomy. Did you examine this in your study? Did you examine how often the spleen was positive in staging laparotomy? Have you examined hemisplenectomy or even the need to preserve the spleen in selected patients, and is there a role for laparoscopic staging in these patients? James A. Edney (Omaha, NE): At our institution, which has a very active lymphoma treatment group, the indications for staging laparotomy have fallen off precipitously in the last decade, from about 15 patients a year to less than one or two annually. Have the authors noted this same phenomenon? This appears to be the result of the efficacy of CT scanning, tine needle aspiration, and other diagnostic modalities in contributing to the accuracy of clinical staging. John A. Butler (Torrance, CA): If an abnormality is discovered on the basis of either the CT scan or the lymphangiogram, have the authors attempted using a CT guided needle aspiration to diagnose the presence of intra-abdominal disease? A negative cytology would not be of value, but a positive result would obviate the need for laparotomy.
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Peter C. Muskat (closing): Of the 96 patients that were not offered the procedure, they generally fell into a group in whom the hematology-oncology specialist felt confident about the results of clinical staging and proceeded on to therapy, either radiotherapy and/or chemotherapy. I would imagine a number of them were stage IV or stage I patients. For those patients with B-type symptoms, yes, there is an increased incidence of positive intra-abdominal disease. We had only 26 patients that had positive B-type symptoms. We had 25 spleens that showed invasion by Hodgkin’s disease in our positive laparotomy experience, and that was, by far, the most common location for intraabdominal disease. There have been several good
studies to suggest that hemisplenectomy is probably inadequate. Dr. Edney, we considered the number of patients per year during our study, and it was fairly constant. Early in our study, about 1980, we had 14 patients that underwent the procedure during that time. In 1988, we had 12 patients undergo staging laparotomy. The total number of patients with Hodgkin’s lymphoma that we have seen in our institution hasn’t significantly changed, and this may be a statistical anomaly. Dr. Butler, for the most part at our institution, our Pathology Department has not been successful in determining if Hodgkin’s disease is present on the basis of fine-needle aspirate of the lymph node.
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