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Thymectomy for myasthenia gravis in older patients
340
Letters to the Editor
and gives rise to the diagnosis of this disease state in 11 of 217 patients (5%).3 This group of patients has a 90% 5-year disease-free survival by our statistics. Also, patients with colon cancer (especially the mucinous type), peritoneal mesothelioma, and ovarian cancer can present with an umbilical protuberance. These patients can be treated with surgery and intraperitoneal chemotherapy for cure in a respectable proportion of patients.4 In summary, Sister Mary Joseph’s sign, a cancerous nodule in the umbilicus, is a manifestation of peritoneal seeding, usually from a mucinous adenocarcinoma. It can be caused by a variety of intraabdominal malignancies. It should be thought to have the same mechanism of formation as the Krukenberg’s syndrome, a cystic ovarian mass that is a manifestation of gastrointestinal cancer. It does not have a dismal prognosis but indicates that special treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy are necessary. REFERENCES 1. Foster MA, Gering SA, Bradley YC. Sister Mary Joseph’s sign from metastatic disease of the pancreas. J Am Coll Surg 2001;192:130. 2. Sittig KM, Rohr MS, McDonald JC. Abdominal wall, umbilicus, peritoneum, mesenteries, omentum, and retroperitoneum. In: Sabiston DC Jr, ed. Textbook of surgery. The biological basis of modern surgical practice. 14th ed. Philadelphia: WB Saunders Co; 1991:728. 3. Esquivel J, Sugarbaker PH. Clinical presentation of the pseudomyxoma peritonei syndrome. Br J Surg 2000;87:1414–1418. 4. Sugarbaker PH. Management of peritoneal surface malignancy: the surgeon’s role. Langenbeck’s Arch Surg 1999;384:576–587.
Thymectomy for Myasthenia Gravis in Older Patients Donald B Sanders, MD, Duke University, Henry J Kaminski, MD, University Hospitals of Cleveland, Alfred Jaretzki III, MD, FACS, Columbia University, Lawrence H Phillips II, MD, University of Virginia, the Evaluation Standards Review Committee, Medical Scientific Advisory Board, Myasthenia Gravis Foundation of America, Inc. In a recent issue of this journal, Abt and colleagues1 reported the experience at their institution performing
J Am Coll Surg
thymectomy in older patients with myasthenia gravis (MG). The efficacy of thymectomy was assessed by changes in the Osserman score, the rate of drug-free or drug-dependent remissions, and the reduction in medication requirements after thymectomy. It is implied that thymectomy is of known, or at least accepted, benefit in the treatment of MG in young patients, with which their results in older patients are compared. They concluded that increased age does not alter the outcomes of thymectomy for MG. The problems with this report are: 1. It is a retrospective study and does not address the extreme variability and unpredictability of MG, the differing response to treatment among patients with different subtypes of MG, or the bias inherent in the selection of patients for thymectomy. Comparison with a control group of patients is mandatory. 2. Their patients did not follow a predefined schedule of medications and dose reduction and the ultimate drug dose is not compared with a control group. These are required in assessing the additive benefit from thymectomy to patients who are receiving immunosuppression. When patients continue to take immunosuppressive medications after thymectomy, it is not possible to infer retrospectively what contribution to the ultimate result was made by thymectomy per se. 3. Objective criteria, such as a quantitative scoring system, are required in the assessment of therapy. The use of the Osserman or other similar clinical classifications is not a reliable measure. The Osserman classification was developed to describe typical clinical patterns in MG.2 As with the authors’ modification of this system, the Osserman system incorporates assessments of severity, disease distribution, and time course. This system is not linear and is not well-suited to describe changes in disease severity. For example, the authors’ class IV and V are defined by disease progression at a point before treatment was begun rather than by severity. 4. Remission is defined as “asymptomatic without medication” without reference to length of time the remission was maintained. Although drug-free remission is an appropriate measure of response to thymectomy in retrospective studies, it is essential that the definition be based on objective criteria, signs, and symptoms, and that the remission be maintained for at least 1year. It should also be recognized that spontaneous remission has been reported in 10% to 20% of patients with untreated MG. 5. Although thymectomy is considered of benefit in young patients based on clinical observations and retrospective
Vol. 193, No. 3, Month 2001
studies, as pointed out in a recent metaanalysis,3 prospective studies are required to definitively prove this benefit.
In summary, the assessment of treatment efficacy in MG presents numerous methodologic challenges. Evaluation of thymectomy has been hampered by a lack of well-defined and widely accepted objective definitions of disease severity and response to therapy. Because MG is an extremely variable and unpredictable illness, comparison with a control group of patients is mandatory and prospective studies are required. A Task Force of the Myasthenia Gravis Foundation of America has recently published recommendations for research standards in MG, which include definitions of clinical classification, disease severity, and postintervention status.4-6 It is urged that future reports of treatment in MG, including those of thymectomy, incorporate the concepts delineated in this report.
Letters to the Editor
341
REFERENCES 1. Abt PL, Patel HJ, Marsh A, Schwartz SI. Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience. J Am Coll Surg 2001;192:459– 464. 2. Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 1971;38:497–537. 3. Gronseth S, Barohn RJ. Practice parameters: thymectomy for autoimmune myasthenia gravis (an evidence base review). Neurology 2000;55:7–15. 4. Task Force, Myasthenia Gravis Foundation of America, Inc. Myasthenia gravis: recommendations for clinical research standards. Neurology 2000;55:16–23. 5. Jaretzki A III, Barohn RB, Ernstoff RM, et al Myasthenia gravis: recommendations for clinical research standards. Ann Thorac Surg 2000;70:327–334. 6. Weinberg A, Gelijns A, Moskowitz A, Jaretzki A. Myasthenia gravis: outcomes analysis. www.neurology.org; 2000 (also available from the Myasthenia Gravis Foundation, 5841 Cedar Lake Rd, [Suite 204], Minneapolis, MN 55416).
Letters to the Editor
and gives rise to the diagnosis of this disease state in 11 of 217 patients (5%).3 This group of patients has a 90% 5-year disease-free survival by our statistics. Also, patients with colon cancer (especially the mucinous type), peritoneal mesothelioma, and ovarian cancer can present with an umbilical protuberance. These patients can be treated with surgery and intraperitoneal chemotherapy for cure in a respectable proportion of patients.4 In summary, Sister Mary Joseph’s sign, a cancerous nodule in the umbilicus, is a manifestation of peritoneal seeding, usually from a mucinous adenocarcinoma. It can be caused by a variety of intraabdominal malignancies. It should be thought to have the same mechanism of formation as the Krukenberg’s syndrome, a cystic ovarian mass that is a manifestation of gastrointestinal cancer. It does not have a dismal prognosis but indicates that special treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy are necessary. REFERENCES 1. Foster MA, Gering SA, Bradley YC. Sister Mary Joseph’s sign from metastatic disease of the pancreas. J Am Coll Surg 2001;192:130. 2. Sittig KM, Rohr MS, McDonald JC. Abdominal wall, umbilicus, peritoneum, mesenteries, omentum, and retroperitoneum. In: Sabiston DC Jr, ed. Textbook of surgery. The biological basis of modern surgical practice. 14th ed. Philadelphia: WB Saunders Co; 1991:728. 3. Esquivel J, Sugarbaker PH. Clinical presentation of the pseudomyxoma peritonei syndrome. Br J Surg 2000;87:1414–1418. 4. Sugarbaker PH. Management of peritoneal surface malignancy: the surgeon’s role. Langenbeck’s Arch Surg 1999;384:576–587.
Thymectomy for Myasthenia Gravis in Older Patients Donald B Sanders, MD, Duke University, Henry J Kaminski, MD, University Hospitals of Cleveland, Alfred Jaretzki III, MD, FACS, Columbia University, Lawrence H Phillips II, MD, University of Virginia, the Evaluation Standards Review Committee, Medical Scientific Advisory Board, Myasthenia Gravis Foundation of America, Inc. In a recent issue of this journal, Abt and colleagues1 reported the experience at their institution performing
J Am Coll Surg
thymectomy in older patients with myasthenia gravis (MG). The efficacy of thymectomy was assessed by changes in the Osserman score, the rate of drug-free or drug-dependent remissions, and the reduction in medication requirements after thymectomy. It is implied that thymectomy is of known, or at least accepted, benefit in the treatment of MG in young patients, with which their results in older patients are compared. They concluded that increased age does not alter the outcomes of thymectomy for MG. The problems with this report are: 1. It is a retrospective study and does not address the extreme variability and unpredictability of MG, the differing response to treatment among patients with different subtypes of MG, or the bias inherent in the selection of patients for thymectomy. Comparison with a control group of patients is mandatory. 2. Their patients did not follow a predefined schedule of medications and dose reduction and the ultimate drug dose is not compared with a control group. These are required in assessing the additive benefit from thymectomy to patients who are receiving immunosuppression. When patients continue to take immunosuppressive medications after thymectomy, it is not possible to infer retrospectively what contribution to the ultimate result was made by thymectomy per se. 3. Objective criteria, such as a quantitative scoring system, are required in the assessment of therapy. The use of the Osserman or other similar clinical classifications is not a reliable measure. The Osserman classification was developed to describe typical clinical patterns in MG.2 As with the authors’ modification of this system, the Osserman system incorporates assessments of severity, disease distribution, and time course. This system is not linear and is not well-suited to describe changes in disease severity. For example, the authors’ class IV and V are defined by disease progression at a point before treatment was begun rather than by severity. 4. Remission is defined as “asymptomatic without medication” without reference to length of time the remission was maintained. Although drug-free remission is an appropriate measure of response to thymectomy in retrospective studies, it is essential that the definition be based on objective criteria, signs, and symptoms, and that the remission be maintained for at least 1year. It should also be recognized that spontaneous remission has been reported in 10% to 20% of patients with untreated MG. 5. Although thymectomy is considered of benefit in young patients based on clinical observations and retrospective
Vol. 193, No. 3, Month 2001
studies, as pointed out in a recent metaanalysis,3 prospective studies are required to definitively prove this benefit.
In summary, the assessment of treatment efficacy in MG presents numerous methodologic challenges. Evaluation of thymectomy has been hampered by a lack of well-defined and widely accepted objective definitions of disease severity and response to therapy. Because MG is an extremely variable and unpredictable illness, comparison with a control group of patients is mandatory and prospective studies are required. A Task Force of the Myasthenia Gravis Foundation of America has recently published recommendations for research standards in MG, which include definitions of clinical classification, disease severity, and postintervention status.4-6 It is urged that future reports of treatment in MG, including those of thymectomy, incorporate the concepts delineated in this report.
Letters to the Editor
341
REFERENCES 1. Abt PL, Patel HJ, Marsh A, Schwartz SI. Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience. J Am Coll Surg 2001;192:459– 464. 2. Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 1971;38:497–537. 3. Gronseth S, Barohn RJ. Practice parameters: thymectomy for autoimmune myasthenia gravis (an evidence base review). Neurology 2000;55:7–15. 4. Task Force, Myasthenia Gravis Foundation of America, Inc. Myasthenia gravis: recommendations for clinical research standards. Neurology 2000;55:16–23. 5. Jaretzki A III, Barohn RB, Ernstoff RM, et al Myasthenia gravis: recommendations for clinical research standards. Ann Thorac Surg 2000;70:327–334. 6. Weinberg A, Gelijns A, Moskowitz A, Jaretzki A. Myasthenia gravis: outcomes analysis. www.neurology.org; 2000 (also available from the Myasthenia Gravis Foundation, 5841 Cedar Lake Rd, [Suite 204], Minneapolis, MN 55416).