<b>Some Annotated Medical Journal Citations </b>

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1. Gynecol Oncol 1998 Dec;71(3):458-60 
<b>Low-grade endometrial stromal sarcoma preoperative treatment with Depo-Lupron and Megace.</b> 
Scribner DR Jr, Walker JL. 
Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73190, USA. 

Two doses of depot Lupron 7.5mg, and Megace 160mg/day, were given to control bleeding and shrink the low grade, inoperable ESS tumor mass in a 46 year old woman. This neoadjuvant therapy allowed for shrinkage of tumor mass, and surgical resection with a TAH with BSO. Additional research is necessary to define the exact role of chemo, radiation, and hormal therapy.  Copyright 1998 Academic Press. 
&&url PMID: 9887250


2. Surg Today 1996;26(2):138-41 
<b>The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case.</b> 
Uchida T, Nakakawaji K, Sakamoto J, Kojima H, Murakami H, Kato J, Yasue M 
Department of Surgery, Aichi Prefectural Hospital, Kakemachi, Okazaki, Japan. 
 
"A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. ... The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. <b>The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma.</b>" 
&&url PMID: 8919287


3. Fertil Steril 1995 Jul;64(1):191-2 
<b>Fibroid growth in response to high-dose progestogen.</b> 
Harrison-Woolrych M, Robinson R. 
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, United Kingdom. 

"To challenge the conventional belief that leiomyomata are estrogen-dependent tumors by presentation of a case report suggesting high-dose progestogen therapy is associated with a dramatic increase in size of a fibroid uterus. ...One white woman treated with tamoxifen and high-dose megestrol acetate for breast carcinoma... While taking tamoxifen and high-dose megestrol acetate, the patient suffered a dramatic increase in size of her fibroid uterus, which reversed when the progestogen was withdrawn. " [NB both megestrol acetate and tamoxifen have been associated with a tumor flare phenomenon.] 
&&url PMID: 7789558 


4. Clin Endocrinol (Oxf) 1995 Jan;42(1):91-3 
<b>Megestrol-induced Cushing's syndrome.</b> 
Steer KA, Kurtz AB, Honour JW. 
Bloomsbury Department of Chemical Pathology, Middlesex Hospital, London, UK. . 
&&url PMID: 7889638 


5. Eur J Gynaecol Oncol 1993;14(1):44-5 
<b>Response of "benign" metastasizing leiomyoma to progestin withdrawal. Case report.</b>
 Cohen JD, Robins HI. 
Division of Hematology/Oncology Denver Veterans Administration Medical Center. 

"We report a rare case of a benign metastasizing leiomyoma in which progestin therapy permitted or promoted pulmonary metastases, but progestin withdrawal induced a marked tumor regression. The significance of these observations is discussed relative to the estrogen and progesterone receptor positivity of this patient's tumor."
&&url PMID: 8472731 


6. Gynecol Oncol 1989 Nov;35(2):275-8 
<b>Low-grade endometrial stromal sarcoma recurring over three decades.</b> 
Styron SL, Burke TW, Linville WK. 
Department of Obstetrics and Gynecology, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200. 
 
"Endometrial stromal sarcoma (ESS) is an uncommon uterine malignancy with a variety of histologic characteristics and clinical courses. We describe a patient who recently underwent her third resection of a locally recurring low-grade ESS 29 years after original diagnosis. Tissue from her recurrent tumor contained high levels of estrogen and progesterone receptors and had a diploid DNA content. In addition to multiple resections, she has previously been treated with vincristine chemotherapy and is now receiving megestrol acetate therapy. Mitotic activity is the most important prognostic feature distinguishing high- and low-grade ESS. The mainstay of therapy for both high- and low-grade tumors is surgical excision. A beneficial adjuvant role for cytotoxic chemotherapy or radiotherapy is yet to be clearly established for low-grade ESS; however, recent reports suggest that progestational agents may produce significant responses in recurrent or persistent disease patients whose tumors produce steroid hormone receptors. Indolent tumors may require years of close observation and multiple treatment approaches to maintain a patient in a functional capacity." 
&&url PMID: 2807024


7. Gan To Kagaku Ryoho 1987 Oct;14(10):2837-44 
<b>[Hormone dependency and progestogen therapy in the treatment of endometrial cancer]. [Article in Japanese]</b> 
Okada H, Nakata Y, Fujimoto J, Fujita H. 
Dept. of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine. 

"The anti-tumor activities of steroid compounds on endometrical cancer (Ishikawa cell line) were examined in vitro by human tumor clonogenic assay (HT CA). Clinically effective progestational compounds including medroxyprogesterone acetate (MAP), and 17 alpha hydroxy-progesterone caproate were effective. Norethindrone (ENT), which is also a potent progestational compound, and RU486, which is known to be a progesterone antagonist were ineffective in this in vitro system, neither having any influence on the effect of MAP. These results indicated that the anti-tumor activity of MAP did not proceed via the so-called progesterone receptor system. Morphological changes induced by MAP in undifferentiated endometrial cancer, the effectiveness of tamoxifen, hormonochemotherapy, and the use of MAP for adjuvant therapy and prophylaxis were also discussed." 
&&url PMID: 2959204 


8. Gynecol Oncol 1987 Jan;26(1):87-97 
<b>Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors.</b> 
Katz L, Merino MJ, Sakamoto H, Schwartz PE.   

"All four of the patients who were treated with hormonal therapy [megestrol acetate] are alive, free of disease, or with stable tumor from 2 to 6 years after diagnosis. The presence of estrogen receptors (ER) and progestin receptors (PR) was demonstrated in the tumor in some of the cases; this may explain the sensitivity of this neoplasm to hormonal therapy." 
&&url PMID: 3792939


9. Semin Oncol 1985 Mar;12(1 Suppl 1):23-7 
<b>Progestin therapy in lesions of the endometrium.</b> 
Wentz WB.  

"This paper details several studies of the effect of a single progestin, megestrol acetate, in patients with persistent endometrial hyperplasia and recurrent or persistent endometrial adenocarcinoma. Results of these studies indicate that megestrol acetate inhibits recurrence of adenomatous and atypical hyperplasia as well as adenocarcinoma in situ. These diseases when left untreated often progress to invasive adenocarcinoma. Additional studies presented here show that megestrol acetate is effective in the treatment of endometrial adenocarcinoma in inoperable patients and increases survival in patients with recurrent endometrial cancer." 
&&url PMID: 3975648


10. Am J Obstet Gynecol 1983 Jun 1;146(3):316-22 
<b>Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia.</b> 
Gal D, Edman CD, Vellios F, Forney JP.  

"Fifty-two postmenopausal women who were poor surgical risks and had histologically proved adenomatous hyperplasia, atypical hyperplasia, or adenocarcinoma in situ of the endometrium were treated with megestrol acetate, 40 mg per day, continuously for 9 to 104 months (mean, 42 months). More than 90% of these women had complete remissions of the hyperplasia. Three women with carcinoma in situ were followed up for 57, 65, and 104 months, without recurrence of the disease. Four women required hysterectomy; none had invasive adenocarcinoma. No adverse side effects of the drug were observed. Thus, we conclude that the continuous use of megestrol acetate is an effective, safe, alternative form of therapy for endometrial hyperplasia in postmenopausal women. " 
&&url PMID: 6859142
