- Email: [email protected]
Long-term outcome of placental-site trophoblastic tumours
Comment
and is better tolerated than exenatide; therefore, this novel GLP-1 analogue might be a good option for the treatment of type 2 diabetes.
4
5
*Christophe E M De Block, Luc F Van Gaal Antwerp University Hospital and University of Antwerp, Department of Diabetology and Endocrinology, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium [email protected] LVG is a member of the Obesity advisory board of Novo Nordisk and of the European Diabetes advisory board of Eli Lilly. CDB declares that he has no conflicts of interest. 1 2 3
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577–89. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580–91. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–80.
6
7 8 9
10
Van Gaal LF, Gutkin SW, Nauck MA. Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide-1 receptor agonists or insulin for patients with inadequate glycemic control. Eur J Endocrinol 2008; 158: 773–84. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week, randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; published online June 8. DOI:10.1016/S0140-6736(09)60659-0. Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ ac/09/briefing/2009-4422b2-02-NovoNordisk.pdf (accessed May 11, 2009). Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008; 358: 1970–71; discussion 1971–72. Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ ac/09/briefing/2009-4422b2-01-FDA.pdf (accessed May 11, 2009). Costante G, Durante C, Francis Z, Schlumberger M, Filetti S. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab 2009; 5: 35–44. Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association, European Association for the Study of Diabetes. Diabetologia 2009; 52: 17–30.
Long-term outcome of placental-site trophoblastic tumours Published Online June 23, 2009 DOI:10.1016/S01406736(09)60791-1
Science Photo Library
See Articles page 48
6
In The Lancet today, Peter Schmid and colleagues describe their long-term experience in the UK of the management of placental-site trophoblastic tumours.1 The report comes from the gestational trophoblastic disease centres at Charing Cross Hospital in London and Weston Park Hospital in Sheffield that serve patients with gestational trophoblastic disease in the UK, by mandate of the Royal College of Obstetricians and Gynaecologists and the Department of Health. Placental-site trophoblastic tumour is the second most rare of gestational trophoblastic neoplasms, accounting for only 0·5% of patients with gestational trophoblastic disease worldwide.2
Just 50 years have passed since choriocarcinoma was first treated successfully and its almost universal mortality was reversed. Now, in the early 21st century, survival is greater than 90%, even in advanced disease.3,4 Gestational trophoblastic disease includes hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour, and epithelioid trophoblastic tumour. These last three disorders can follow a hydatidiform mole or arise de novo after any pregnancy event. Human chorionic gonadotropin (hCG) is a reliable marker of the persistence of trophoblast cells, and the concentration of hCG precisely correlates with tumour load. The term trophoblastic neoplasia is used when trophoblastic cells are not destroyed spontaneously after evacuation of a hydatidiform mole, so causing persistence of hCG and, by implication, trophoblastic neoplasia. Histological confirmation of invasive mole is therefore no longer mandatory and the hCG regression curve5 is used to make the diagnosis of trophoblastic neoplasia. The International Federation of Gynecology and Obstetrics promulgated a staging and risk-factor scoring system for trophoblastic neoplasia in 2002, which is in worldwide use.5 Single-agent chemotherapy cures 99·9% of such patients, provided that the treating physician is familiar with the management of gestational trophoblastic disease and the patient is compliant.2 The term trophoblastic neoplasia supersedes terms such as invasive mole, malignant trophoblastic disease, and www.thelancet.com Vol 374 July 4, 2009
Comment
trophoblastic tumour. These advances have become possible because of the ability to measure tumour load with hCG, diagnose hydatidiform mole in early pregnancy by ultrasound, and the ability to determine whether or not metastases are present on CT and MRI, together with greater understanding of the pathology and molecular physiology of trophoblastic neoplasia.6 Schmid and colleagues focus on a rare entity of trophoblastic neoplasia, which is placental-site trophoblastic tumour. The condition was first described in 1976 and named trophoblastic pseudotumour,7 and was thought to be benign. It was not until 1981 that Twiggs and colleagues8 encountered a patient who had metastases, and in 1982 Eckstein and colleagues9 reported four further cases from Charing Cross Hospital. Most reports since then have been case reports or the small number of patients that are cited in today’s report. It is now accepted that placental-site trophoblastic tumours differ from other trophoblastic neoplasms in that the tumour load is not accurately correlated with the concentration of hCG, and that the tumour might be less sensitive to chemotherapy that is effective in the other types of trophoblastic neoplasia. Placentalsite trophoblastic tumours might follow any type of pregnancy event, not infrequently becoming clinically apparent even years later, and there is great variability in its malignant aggressiveness. The neoplasm arises from intermediate trophoblast, unlike choriocarcinoma, which arises from villous trophoblast. There can be difficulty with the diagnosis if access to biopsy is not easy, and there is difficulty in histological differentiation of placental-site trophoblastic tumours from the other trophoblastic neoplasms. Unlike with postmolar trophoblastic neoplasia, precise histological diagnosis is essential. Immunohistological staining for human
placental lactogen and hCG is especially helpful. Raised free β-hCG concentration in serum can also point to the diagnosis when germ-cell tumours of the ovary and other cancer entities can be excluded by clinical examination and imaging.10 What Schmid and colleagues show more convincingly than was previously evident is that the greater the interval between the index pregnancy and appearance of overt neoplasia, the more likely the disease will be aggressive. It is gratifying to find that the investigators advocate adjuvant chemotherapy even for stage I disease. Ernest I Kohorn Department of Gynecology, Yale University School of Medicine, New Haven, CT 06510, USA [email protected] I declare that I have no conflicts of interest. 1
2 3
4 5
6
7 8
9
10
Schmid P, Nagai Y, Agarwal R, et al. Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 2009; published online June 23. DOI:10.1016/ S0140-6736(09)60618-8. Kohorn EI. World-wide results of therapy for gestational trophoblastic disease. Gynecol Oncol 2009; 112 (suppl 1): 85 (abstr). Hertz R, Bergenstal DM, Lipsett MB, Price EB, Hilbish TF. Chemotherapy of choriocarcinoma and related trophoblastic tumors in women. Ann N Y Acad Sci 1959; 80: 262–77. Bagshawe KD, Brooks WDW. Subacute pulmonary hypertension due to chorionepithelioma. Lancet 1959; 1: 653–58. Kohorn EI. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment. Int J Gynecol Cancer 2001; 11: 73–77. Hancock EW, Newlands ES, Berkowitz RS, Cole LA, eds. Gestational trophoblastic disease, 2nd edn. 2008. http://www.isstd.org/gtd/contents. html (accessed April 24, 2009). Kurman RJ, Scully RE, Norris HJ. Trophoblastic pseudotumor of the uterus. Cancer 1976; 38: 1214–26. Twiggs LB, Okagaki T, Philips GL, Stroemer JR, Adcock LL. Trophoblastic pseudotumor—evidence of malignant disease potential. Gynecol Oncol 1981; 12: 238–48. Eckstein RP, Paradinas FJ, Bagshawe KD. Placental site trophoblastic tumour (trophoblastic pseudotumour): a study of four cases requiring hysterectomy including one fatal case. Histopathology 1982; 6: 211–26. Cole LA, Khanlian SA, Muller CY, Giddings A, Kohorn E, Berkowitz R. Gestational trophoblastic diseases: 3. Human chorionic gonadotropin free β-subunit, a reliable marker of placental site trophoblastic tumors. Gynecol Oncol 2006; 102: 160–64.
NECT trial: more than a small victory over sleeping sickness The natural history of central nervous system infection by Trypanosoma brucei gambiense consists of a distinctive neurological syndrome (sleeping sickness) proceeding to inevitable death. For more than 50 years intravenous melarsoprol has been the most common therapeutic approach, but this arsenical compound can cause a reactive encephalopathy with high risk of www.thelancet.com Vol 374 July 4, 2009
mortality and shows falling efficacy in certain areas.1 Eflornithine is an efficacious alternative with fewer sideeffects,2–4 but the need for its 6-hourly administration via slow infusion, over 14 days, has limited uptake in resource-poor settings. Oral nifurtimox shows too low an efficacy for routine use as monotherapy5 but has been tested recently in combination with eflornithine,
Published Online June 25, 2009 DOI:10.1016/S01406736(09)61163-6 See Articles page 56
7
and is better tolerated than exenatide; therefore, this novel GLP-1 analogue might be a good option for the treatment of type 2 diabetes.
4
5
*Christophe E M De Block, Luc F Van Gaal Antwerp University Hospital and University of Antwerp, Department of Diabetology and Endocrinology, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium [email protected] LVG is a member of the Obesity advisory board of Novo Nordisk and of the European Diabetes advisory board of Eli Lilly. CDB declares that he has no conflicts of interest. 1 2 3
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577–89. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580–91. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–80.
6
7 8 9
10
Van Gaal LF, Gutkin SW, Nauck MA. Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide-1 receptor agonists or insulin for patients with inadequate glycemic control. Eur J Endocrinol 2008; 158: 773–84. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week, randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; published online June 8. DOI:10.1016/S0140-6736(09)60659-0. Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ ac/09/briefing/2009-4422b2-02-NovoNordisk.pdf (accessed May 11, 2009). Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008; 358: 1970–71; discussion 1971–72. Food and Drug Administration. http://www.fda.gov/ohrms/dockets/ ac/09/briefing/2009-4422b2-01-FDA.pdf (accessed May 11, 2009). Costante G, Durante C, Francis Z, Schlumberger M, Filetti S. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab 2009; 5: 35–44. Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association, European Association for the Study of Diabetes. Diabetologia 2009; 52: 17–30.
Long-term outcome of placental-site trophoblastic tumours Published Online June 23, 2009 DOI:10.1016/S01406736(09)60791-1
Science Photo Library
See Articles page 48
6
In The Lancet today, Peter Schmid and colleagues describe their long-term experience in the UK of the management of placental-site trophoblastic tumours.1 The report comes from the gestational trophoblastic disease centres at Charing Cross Hospital in London and Weston Park Hospital in Sheffield that serve patients with gestational trophoblastic disease in the UK, by mandate of the Royal College of Obstetricians and Gynaecologists and the Department of Health. Placental-site trophoblastic tumour is the second most rare of gestational trophoblastic neoplasms, accounting for only 0·5% of patients with gestational trophoblastic disease worldwide.2
Just 50 years have passed since choriocarcinoma was first treated successfully and its almost universal mortality was reversed. Now, in the early 21st century, survival is greater than 90%, even in advanced disease.3,4 Gestational trophoblastic disease includes hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour, and epithelioid trophoblastic tumour. These last three disorders can follow a hydatidiform mole or arise de novo after any pregnancy event. Human chorionic gonadotropin (hCG) is a reliable marker of the persistence of trophoblast cells, and the concentration of hCG precisely correlates with tumour load. The term trophoblastic neoplasia is used when trophoblastic cells are not destroyed spontaneously after evacuation of a hydatidiform mole, so causing persistence of hCG and, by implication, trophoblastic neoplasia. Histological confirmation of invasive mole is therefore no longer mandatory and the hCG regression curve5 is used to make the diagnosis of trophoblastic neoplasia. The International Federation of Gynecology and Obstetrics promulgated a staging and risk-factor scoring system for trophoblastic neoplasia in 2002, which is in worldwide use.5 Single-agent chemotherapy cures 99·9% of such patients, provided that the treating physician is familiar with the management of gestational trophoblastic disease and the patient is compliant.2 The term trophoblastic neoplasia supersedes terms such as invasive mole, malignant trophoblastic disease, and www.thelancet.com Vol 374 July 4, 2009
Comment
trophoblastic tumour. These advances have become possible because of the ability to measure tumour load with hCG, diagnose hydatidiform mole in early pregnancy by ultrasound, and the ability to determine whether or not metastases are present on CT and MRI, together with greater understanding of the pathology and molecular physiology of trophoblastic neoplasia.6 Schmid and colleagues focus on a rare entity of trophoblastic neoplasia, which is placental-site trophoblastic tumour. The condition was first described in 1976 and named trophoblastic pseudotumour,7 and was thought to be benign. It was not until 1981 that Twiggs and colleagues8 encountered a patient who had metastases, and in 1982 Eckstein and colleagues9 reported four further cases from Charing Cross Hospital. Most reports since then have been case reports or the small number of patients that are cited in today’s report. It is now accepted that placental-site trophoblastic tumours differ from other trophoblastic neoplasms in that the tumour load is not accurately correlated with the concentration of hCG, and that the tumour might be less sensitive to chemotherapy that is effective in the other types of trophoblastic neoplasia. Placentalsite trophoblastic tumours might follow any type of pregnancy event, not infrequently becoming clinically apparent even years later, and there is great variability in its malignant aggressiveness. The neoplasm arises from intermediate trophoblast, unlike choriocarcinoma, which arises from villous trophoblast. There can be difficulty with the diagnosis if access to biopsy is not easy, and there is difficulty in histological differentiation of placental-site trophoblastic tumours from the other trophoblastic neoplasms. Unlike with postmolar trophoblastic neoplasia, precise histological diagnosis is essential. Immunohistological staining for human
placental lactogen and hCG is especially helpful. Raised free β-hCG concentration in serum can also point to the diagnosis when germ-cell tumours of the ovary and other cancer entities can be excluded by clinical examination and imaging.10 What Schmid and colleagues show more convincingly than was previously evident is that the greater the interval between the index pregnancy and appearance of overt neoplasia, the more likely the disease will be aggressive. It is gratifying to find that the investigators advocate adjuvant chemotherapy even for stage I disease. Ernest I Kohorn Department of Gynecology, Yale University School of Medicine, New Haven, CT 06510, USA [email protected] I declare that I have no conflicts of interest. 1
2 3
4 5
6
7 8
9
10
Schmid P, Nagai Y, Agarwal R, et al. Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 2009; published online June 23. DOI:10.1016/ S0140-6736(09)60618-8. Kohorn EI. World-wide results of therapy for gestational trophoblastic disease. Gynecol Oncol 2009; 112 (suppl 1): 85 (abstr). Hertz R, Bergenstal DM, Lipsett MB, Price EB, Hilbish TF. Chemotherapy of choriocarcinoma and related trophoblastic tumors in women. Ann N Y Acad Sci 1959; 80: 262–77. Bagshawe KD, Brooks WDW. Subacute pulmonary hypertension due to chorionepithelioma. Lancet 1959; 1: 653–58. Kohorn EI. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment. Int J Gynecol Cancer 2001; 11: 73–77. Hancock EW, Newlands ES, Berkowitz RS, Cole LA, eds. Gestational trophoblastic disease, 2nd edn. 2008. http://www.isstd.org/gtd/contents. html (accessed April 24, 2009). Kurman RJ, Scully RE, Norris HJ. Trophoblastic pseudotumor of the uterus. Cancer 1976; 38: 1214–26. Twiggs LB, Okagaki T, Philips GL, Stroemer JR, Adcock LL. Trophoblastic pseudotumor—evidence of malignant disease potential. Gynecol Oncol 1981; 12: 238–48. Eckstein RP, Paradinas FJ, Bagshawe KD. Placental site trophoblastic tumour (trophoblastic pseudotumour): a study of four cases requiring hysterectomy including one fatal case. Histopathology 1982; 6: 211–26. Cole LA, Khanlian SA, Muller CY, Giddings A, Kohorn E, Berkowitz R. Gestational trophoblastic diseases: 3. Human chorionic gonadotropin free β-subunit, a reliable marker of placental site trophoblastic tumors. Gynecol Oncol 2006; 102: 160–64.
NECT trial: more than a small victory over sleeping sickness The natural history of central nervous system infection by Trypanosoma brucei gambiense consists of a distinctive neurological syndrome (sleeping sickness) proceeding to inevitable death. For more than 50 years intravenous melarsoprol has been the most common therapeutic approach, but this arsenical compound can cause a reactive encephalopathy with high risk of www.thelancet.com Vol 374 July 4, 2009
mortality and shows falling efficacy in certain areas.1 Eflornithine is an efficacious alternative with fewer sideeffects,2–4 but the need for its 6-hourly administration via slow infusion, over 14 days, has limited uptake in resource-poor settings. Oral nifurtimox shows too low an efficacy for routine use as monotherapy5 but has been tested recently in combination with eflornithine,
Published Online June 25, 2009 DOI:10.1016/S01406736(09)61163-6 See Articles page 56
7