- Email: [email protected]
Positron emission tomography and uterine leiomyomas
Letters to the Editor
malignancy rarely had the diagnosis made preoperatively. Rather, the majority of patients presented with an adnexal mass and were operated on initially by a gynecologic oncologist. All too often, these patients were thought to have mucinous ovarian neoplasms and were staged accordingly. Typically, histologic review of the surgical specimens postoperatively revealed a primary tumor in the appendix, often with ovarian and peritoneal metastases. As a result, many patients had to undergo a subsequent operation with hemicolectomy and/ or tumor debulking. In a letter to the editor by Lambert and Mansfield [2], the authors provide important data concerning the optimal treatment of these patients. First, despite peritoneal spread, non-carcinoid epithelial tumors of the appendix tend not to metastasize to other intra-abdominal organs, and are relatively slow growing. Most importantly, a combined approach of aggressive cytoreductive surgery and intraperitoneal chemotherapy can result in prolonged disease-free survival in a significant number of patients. The importance of aggressive tumor debulking was suggested in a prospective randomized trial from the Netherlands Cancer Institute [3]. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was compared to systemic chemotherapy with or without palliative surgery in 105 patients with peritoneal metastases from colorectal adenocarcinoma. Patients assigned to the aggressive treatment arm had a statistically significant increase in survival (22.3 months versus 12.6 months). In a subsequent study, Stewart and colleagues [4] reported the efficacy of this approach in patients with primary appendiceal cancer. Cytoreductive surgery involved the removal of all gross tumor including the peritoneum, omentum, and involved organs, when feasible. Tumors that could not be removed were cytoreduced, using the cavitational ultrasonic surgical aspirator. After tumor debulking was completed, peritoneal inflow and outflow catheters attached to temperature probes were placed percutaneously into the abdominal cavity. Patients then were treated with a perfusate containing 40 mg of mitocycin-C over 120 min at a peritoneal temperature of approximately 40 °C. This treatment regimen was associated with a 1-year survival rate of 79.9% and a 5-year survival rate of 53.4%. There was a positive correlation between survival and the patient's preoperative performance status, as well as the ability of the surgeon to achieve complete tumor debulking. However, cytoreductive surgery was often challenging, and was associated with a 30-day postoperative morbidity of 38% and a mortality rate of 4%. Similarity between the treatment of advanced ovarian and primary appendiceal cancers with peritoneal spread is evident particularly with respect to the use of aggressive tumor debulking followed by postoperative intraperitoneal chemotherapy. However, the specific chemotherapeutic agents used are quite different as is the more established role of hyperthermia in patients with primary appendiceal cancer [5]. For this reason, the appendix should be removed and evaluated intraoperatively in all women presenting with a mucinous adenocarcinoma involving both ovaries and the peritoneum. If
593
adenocarcinoma is identified in the mucosa of the appendix, the diagnosis of primary appendiceal cancer can be established and the patient staged and treated as recommended. As mentioned by Lambert and Mansfield [2], if the surgeons involved are not experienced in the management of these cases, it may be preferable after staging to refer the patient to an institution with a peritoneal surface oncology program.
References [1] Dietrich CS, DeSimone CP, Modesitt S, DePriest PD, Ueland FR, Pavlik EJ, et al. Primary appendiceal cancer: gynecologic manifestations and treatment options. Gynecol Oncol 2007;104:602–6. [2] Lambert LA, Mansfield PF. Peritoneal dissemination of non-carcinoid primary appendiceal cancer. Gynecol Oncol 2007;107:592. [3] Verwall VJ, van Ruth S, deBree E, van Slooten GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003;21:3737–43. [4] Stewart JH, Shen P, Russell GB, Bradley RF, Hundley JC, Loggie BL, et al. Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Ann Surg Oncol 2006;13(5):624–34. [5] Levine EA, Stewart JH, Russell GB, Geisinger KR, Loggie BL, Shen P. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204:943–55.
J.R. van Nagell Jr.* C.P. DeSimone Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center–Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0298, USA E-mail address: [email protected]. ⁎Corresponding author. Fax: +1 859 323 1018. 9 July 2007 doi:10.1016/j.ygyno.2007.07.054
Positron emission tomography and uterine leiomyomas
To the Editor: We were interested to read the report by Chura et al. [1] “Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review”. Uterine myomas represent the most common tumor of the female reproductive system but are also the most common indication for hysterectomy. For women who wish to retain childbearing potential, an organ-preserving strategy, including myomectomy, uterine artery ligation or embolization, and so on has been the preferred treatment [2].
594
Letters to the Editor
However, malignant-type leiomyosarcomas should often be kept in mind, although the incidence is rare and the majority of leiomyosarcomas are diagnosed after hysterectomy or myomectomy, at the time of the pathologic review [1]. Therefore, how to distinguish between a leiomyoma and a leiomyosarcoma prior to surgery is an interesting issue and worthy of further evaluation. Many imaging studies, including high-resolution ultrasound, computed tomography and magnetic resonance imaging have been tried. However, none of them are adequate in achieving satisfactory sensitivity or specificity partly due to the small sample size. Although the use of positron emission tomography (PET) in oncologic diagnosis has rekindled interest in this technique [3], the application of PET for distinguishing leiomyomas from leiomyosarcomas is doubtful [1] and needs further evaluation [4]. We welcome Chura et al.'s efforts to explore the pathogenesis of PET scanpositive leiomyomas and observed the striking phenomenon that the PET scan-positive leiomyoma has increased vascularity [1]. However, this striking phenomenon may be the result of an accident. In our previous study, although the data was limited by the very small series (a total of 4 women), 2 women with surgery-proved myomas did not show an increased accumulation of (fluorine-18)-2-deoxygelucose (FDG) in either the normal uterine tissue or the uterine myoma preoperatively [5]. By contrast, the other 2 women, who were treated with 4 courses of gonadotropin-releasing hormone agonist (GnRH agonist) preoperatively, and then received a PET evaluation, demonstrated an increased FDG uptake, with a distribution that correlated with the uterine leiomyoma area, which was proved by myomectomy [5]. The application of GnRH agonist in uterine myoma preoperatively is a well-accepted procedure based on advantages that include a significant decrease of blood loss and easy manipulation [6]. If the increased vascularity is correlated with the PET scan-positive leiomyoma, why were the abovementioned benefits found when we performed myomectomy after GnRH agonist treatment? By contrast, if the increased vascularity of the uterine leiomyoma is real, it may contribute to regrowth of GnRH agonist treated uterine myomas after cessation of therapy [5], although the blood flow change in the uterine myoma before and after GnRH agonist treatment was still inconclusive in literature reviews [7,8]. We hope to see further discussion and suggestions on this issue.
[3] Wang PH, Liu RS, Li YF, Ng HT, Yuan CC. Whole-body PET with (fluorine-18)-2-deoxygelucose for detecting recurrent primary serous peritoneal carcinoma. Gynecol Oncol 2000;77:44–7. [4] Umesaki N, Tanaka T, Miyama M, et al. Positron emission tomography with 18F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging. Gynecol Oncol 2000; 80:372–7. [5] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001; 75:638–9. [6] Palomba S, Zupi E, Zullo F. A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas. J Minim Invasive Gynecol 2006;13:253 [author reply 253–4]. [7] Wang PH, Yang AH, Yuan CC, Ng HT, Chao HT. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. J Chin Med Assoc 1998;61:625–9. [8] Chia CC, Huang SC, Chen SS, Kang JY, et al. Ultrasonographic evaluation of the uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol 2006;45:124–8.
Wen-Ling Lee Division of Endocrinology and Metabolism, Department of Medicine, Cheng Hsin Rehabilitation Center-Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Chiou-Chung Yuan Peng-Hui Wang* Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan *Corresponding author. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 4101. E-mail address: [email protected] 26 June 2007 doi:10.1016/j.ygyno.2007.08.005
Acknowledgments
Positron emission tomography and uterine leiomyomas: Authors' response
This article was supported in part, by Grants from Taipei Veterans General Hospital and National Science Council.
To the Editor:
References [1] Chura JC, Truskinovsky AM, Judson PL, Johnson L, Geller MA, Downs LS. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review. Gynecol Oncol 2007;104:247–52. [2] Liu WM, Wang PH, Chou CS, et al. Efficacy of combined laparoscopic uterine artery occlusion and myomectomy via minilaparotomy in the treatment of recurrent uterine myomas. Fertil Steril 2007;87:356–61.
We appreciate the interest of Dr. Lee and colleagues regarding the issue of PET scans and uterine leiomyomas [1] that we recently presented [2]. This intersection of a widely used diagnostic test and the most common tumor of the female genital tract presents a vexing clinical scenario: How should PET scan positive uterine tumors be managed? Lee et al. introduce another variable into the question above with their use of GnRH agonist therapy in two patients with
malignancy rarely had the diagnosis made preoperatively. Rather, the majority of patients presented with an adnexal mass and were operated on initially by a gynecologic oncologist. All too often, these patients were thought to have mucinous ovarian neoplasms and were staged accordingly. Typically, histologic review of the surgical specimens postoperatively revealed a primary tumor in the appendix, often with ovarian and peritoneal metastases. As a result, many patients had to undergo a subsequent operation with hemicolectomy and/ or tumor debulking. In a letter to the editor by Lambert and Mansfield [2], the authors provide important data concerning the optimal treatment of these patients. First, despite peritoneal spread, non-carcinoid epithelial tumors of the appendix tend not to metastasize to other intra-abdominal organs, and are relatively slow growing. Most importantly, a combined approach of aggressive cytoreductive surgery and intraperitoneal chemotherapy can result in prolonged disease-free survival in a significant number of patients. The importance of aggressive tumor debulking was suggested in a prospective randomized trial from the Netherlands Cancer Institute [3]. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was compared to systemic chemotherapy with or without palliative surgery in 105 patients with peritoneal metastases from colorectal adenocarcinoma. Patients assigned to the aggressive treatment arm had a statistically significant increase in survival (22.3 months versus 12.6 months). In a subsequent study, Stewart and colleagues [4] reported the efficacy of this approach in patients with primary appendiceal cancer. Cytoreductive surgery involved the removal of all gross tumor including the peritoneum, omentum, and involved organs, when feasible. Tumors that could not be removed were cytoreduced, using the cavitational ultrasonic surgical aspirator. After tumor debulking was completed, peritoneal inflow and outflow catheters attached to temperature probes were placed percutaneously into the abdominal cavity. Patients then were treated with a perfusate containing 40 mg of mitocycin-C over 120 min at a peritoneal temperature of approximately 40 °C. This treatment regimen was associated with a 1-year survival rate of 79.9% and a 5-year survival rate of 53.4%. There was a positive correlation between survival and the patient's preoperative performance status, as well as the ability of the surgeon to achieve complete tumor debulking. However, cytoreductive surgery was often challenging, and was associated with a 30-day postoperative morbidity of 38% and a mortality rate of 4%. Similarity between the treatment of advanced ovarian and primary appendiceal cancers with peritoneal spread is evident particularly with respect to the use of aggressive tumor debulking followed by postoperative intraperitoneal chemotherapy. However, the specific chemotherapeutic agents used are quite different as is the more established role of hyperthermia in patients with primary appendiceal cancer [5]. For this reason, the appendix should be removed and evaluated intraoperatively in all women presenting with a mucinous adenocarcinoma involving both ovaries and the peritoneum. If
593
adenocarcinoma is identified in the mucosa of the appendix, the diagnosis of primary appendiceal cancer can be established and the patient staged and treated as recommended. As mentioned by Lambert and Mansfield [2], if the surgeons involved are not experienced in the management of these cases, it may be preferable after staging to refer the patient to an institution with a peritoneal surface oncology program.
References [1] Dietrich CS, DeSimone CP, Modesitt S, DePriest PD, Ueland FR, Pavlik EJ, et al. Primary appendiceal cancer: gynecologic manifestations and treatment options. Gynecol Oncol 2007;104:602–6. [2] Lambert LA, Mansfield PF. Peritoneal dissemination of non-carcinoid primary appendiceal cancer. Gynecol Oncol 2007;107:592. [3] Verwall VJ, van Ruth S, deBree E, van Slooten GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003;21:3737–43. [4] Stewart JH, Shen P, Russell GB, Bradley RF, Hundley JC, Loggie BL, et al. Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Ann Surg Oncol 2006;13(5):624–34. [5] Levine EA, Stewart JH, Russell GB, Geisinger KR, Loggie BL, Shen P. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204:943–55.
J.R. van Nagell Jr.* C.P. DeSimone Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center–Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0298, USA E-mail address: [email protected]. ⁎Corresponding author. Fax: +1 859 323 1018. 9 July 2007 doi:10.1016/j.ygyno.2007.07.054
Positron emission tomography and uterine leiomyomas
To the Editor: We were interested to read the report by Chura et al. [1] “Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review”. Uterine myomas represent the most common tumor of the female reproductive system but are also the most common indication for hysterectomy. For women who wish to retain childbearing potential, an organ-preserving strategy, including myomectomy, uterine artery ligation or embolization, and so on has been the preferred treatment [2].
594
Letters to the Editor
However, malignant-type leiomyosarcomas should often be kept in mind, although the incidence is rare and the majority of leiomyosarcomas are diagnosed after hysterectomy or myomectomy, at the time of the pathologic review [1]. Therefore, how to distinguish between a leiomyoma and a leiomyosarcoma prior to surgery is an interesting issue and worthy of further evaluation. Many imaging studies, including high-resolution ultrasound, computed tomography and magnetic resonance imaging have been tried. However, none of them are adequate in achieving satisfactory sensitivity or specificity partly due to the small sample size. Although the use of positron emission tomography (PET) in oncologic diagnosis has rekindled interest in this technique [3], the application of PET for distinguishing leiomyomas from leiomyosarcomas is doubtful [1] and needs further evaluation [4]. We welcome Chura et al.'s efforts to explore the pathogenesis of PET scanpositive leiomyomas and observed the striking phenomenon that the PET scan-positive leiomyoma has increased vascularity [1]. However, this striking phenomenon may be the result of an accident. In our previous study, although the data was limited by the very small series (a total of 4 women), 2 women with surgery-proved myomas did not show an increased accumulation of (fluorine-18)-2-deoxygelucose (FDG) in either the normal uterine tissue or the uterine myoma preoperatively [5]. By contrast, the other 2 women, who were treated with 4 courses of gonadotropin-releasing hormone agonist (GnRH agonist) preoperatively, and then received a PET evaluation, demonstrated an increased FDG uptake, with a distribution that correlated with the uterine leiomyoma area, which was proved by myomectomy [5]. The application of GnRH agonist in uterine myoma preoperatively is a well-accepted procedure based on advantages that include a significant decrease of blood loss and easy manipulation [6]. If the increased vascularity is correlated with the PET scan-positive leiomyoma, why were the abovementioned benefits found when we performed myomectomy after GnRH agonist treatment? By contrast, if the increased vascularity of the uterine leiomyoma is real, it may contribute to regrowth of GnRH agonist treated uterine myomas after cessation of therapy [5], although the blood flow change in the uterine myoma before and after GnRH agonist treatment was still inconclusive in literature reviews [7,8]. We hope to see further discussion and suggestions on this issue.
[3] Wang PH, Liu RS, Li YF, Ng HT, Yuan CC. Whole-body PET with (fluorine-18)-2-deoxygelucose for detecting recurrent primary serous peritoneal carcinoma. Gynecol Oncol 2000;77:44–7. [4] Umesaki N, Tanaka T, Miyama M, et al. Positron emission tomography with 18F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging. Gynecol Oncol 2000; 80:372–7. [5] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001; 75:638–9. [6] Palomba S, Zupi E, Zullo F. A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas. J Minim Invasive Gynecol 2006;13:253 [author reply 253–4]. [7] Wang PH, Yang AH, Yuan CC, Ng HT, Chao HT. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. J Chin Med Assoc 1998;61:625–9. [8] Chia CC, Huang SC, Chen SS, Kang JY, et al. Ultrasonographic evaluation of the uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol 2006;45:124–8.
Wen-Ling Lee Division of Endocrinology and Metabolism, Department of Medicine, Cheng Hsin Rehabilitation Center-Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Chiou-Chung Yuan Peng-Hui Wang* Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan *Corresponding author. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 4101. E-mail address: [email protected] 26 June 2007 doi:10.1016/j.ygyno.2007.08.005
Acknowledgments
Positron emission tomography and uterine leiomyomas: Authors' response
This article was supported in part, by Grants from Taipei Veterans General Hospital and National Science Council.
To the Editor:
References [1] Chura JC, Truskinovsky AM, Judson PL, Johnson L, Geller MA, Downs LS. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review. Gynecol Oncol 2007;104:247–52. [2] Liu WM, Wang PH, Chou CS, et al. Efficacy of combined laparoscopic uterine artery occlusion and myomectomy via minilaparotomy in the treatment of recurrent uterine myomas. Fertil Steril 2007;87:356–61.
We appreciate the interest of Dr. Lee and colleagues regarding the issue of PET scans and uterine leiomyomas [1] that we recently presented [2]. This intersection of a widely used diagnostic test and the most common tumor of the female genital tract presents a vexing clinical scenario: How should PET scan positive uterine tumors be managed? Lee et al. introduce another variable into the question above with their use of GnRH agonist therapy in two patients with