Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years

BACKGROUND: Epithelial ovarian neoplasms are rare in patients under the age of 21 years. This is a report of a series of such patients documenting their presentation, histologic type, stage of disease, treatment, and outcome. METHODS: Clinical findings, histology, stage, treatment, and outcomes of 19 patients with epithelial ovarian neoplasia are reported. All histology was rereviewed. RESULTS: The median age at the time of diagnosis was 19.7 years (range, 14.1-21.8 years), and the median follow-up was 5.6 years (range, 0.2-19.5 years). The most common presenting symptom was dysmenorrhea (100%) followed by abdominal pain (68%), and the initial diagnosis usually was made ultrasonographically. There were nine (47%) serous tumors, 7 (37%) mucinous tumors, 2 (11%) small cell carcinomas, and 1 (5%) endometrioid carcinoma. Seventy-nine percent of tumors were unilateral, and 84% were low malignant potential or well differentiated tumors. Surgical treatment included unilateral salpingo-oophorectomy in 12 patients (63%), total abdominal hysterectomy and bilateral salpingo-oophorectomy in 6 patients (32%), and ovarian cystectomy in 1 patient (5%). Fifteen patients (79%) had Stage I disease, and 4 patients (21%) had Stage III disease at the time of diagnosis. There were two deaths in this series, and both occurred in patients with small cell anaplastic carcinoma. CONCLUSIONS: Epithelial ovarian neoplasias are rare in patients in this age group but must be included in the differential diagnosis of an ovarian mass. Most patients present with Stage I tumors of low malignant potential. In these patients, good survival is achieved with unilateral salpingo-oophorectomy and preservation of fertility. In contrast, small cell carcinomas are very aggressive, and patients with this variant require intensive therapy.     

Conservative surgery for malignant ovarian tumor in women of childbearing age

Background. The traditional operative procedures for the treatment of ovarian cancer have been simple total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. However, young patients who want to preserve fertility are occasionally encountered. This study was designed to assess the results of conservative surgical management for young women with stage I epithelial ovarian carcinoma or malignant germ cell tumor and to explore the indications for such surgical treatment. Methods. Fifty-eight patients aged under 35 years were treated for malignant ovarian tumors (germ cell tumor, n = 20; epithelial tumors, n = 38) between 1971 and 1996. We studied all 20 patients with germ cell tumors and 22 pa-tients with stage I epithelial tumors; we excluded the 12 patients with stage II and more advanced disease and the 4 patients with stage I clear cell carcinoma, because these patients had poor prognoses. Eleven of the 22 patients with stage I epithelial tumors and 8 of the 20 patients with germ cell tumors received conservative surgery (conservative surgery group); the remaining 23 patients underwent radical surgery, including hysterectomy and bilateral salpingo-oophorectomy (radical surgery group). The overall survival rates of the two groups were compared, and ovarian function and pregnancy outcome were evaluated in the conservative surgery group. Results. Of the patients with malignant epithelial tumor who were treated with conservative surgery, 3 patients with stage Ic mucinous adenocarcinoma died 1 year and 8 months, 7 years and 6 months, and 8 years, respectively, after the initial surgery. The 10-year survival rate was 65% for the conservative surgery group and 91% for the radical surgery group. All patients with stage Ia epithelial tumors in both groups survived, and there were no differences in survival curves between the two groups among the patients with stage Ic epithelial tumors. All patients with germ cell tumors in the conservative surgery group survived. Their survival rate, however, was not significantly better than that in the radical surgery group. All patients with germ cell tumors who received platinum-based chemotherapy survived and had a significantly better survival rate than those who received non-platinum-based regimens (P < 0.05). All the patients in the conservative surgery group received postoperative chemotherapy; 10 of these patients had transient ovulation failure after the completion of chemotherapy, although a normal menstrual cycle was restored within 1 year. Of the 10 patients who wished to have babies, 6 became pregnant, and they have had a total of 11 children. Conclusion. Conservative surgery is feasible in patients with stage Ia epithelial carcinoma and germ cell tumor. Postoperative chemotherapy suppressed ovarian function in these patients, but only for a brief period. Received: January 5, 1999 / Accepted: October 27, 1999     

Ovarian mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type. A clinicopathologic analysis

Borderline tumors with papillae that are architecturally similar to those of serous tumors but with a lining of more than one mullerian cell type have not been well characterized in in the literature. We have studied 36 such tumors. The patients averaged 35 years of age. Twenty-two percent of the tumors were bilateral; all were confined to the ovaries as confirmed at operation. Fifty-three percent were associated with endometriosis. Follow-up information was available on 34 patients for a mean interval of 4.8 years. A tumor developed in the contralateral ovary in one patient 2 years after unilateral salpingo-oophorectomy. Three patients had pelvic recurrences between 7 months and 3 years, but all of them were successfully treated and none have died. These tumors differ clinically and pathologically from intestinal-type mucinous borderline tumors, but they have many similarities with mullerian mucinous borderline tumors and, to a lesser extent, with serous borderline tumors.     

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin

Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo-oophorectomy in ten patients, and bilateral salpingo-oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second-line treatment; three patients had a complete response to therapy and are surviving disease-free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide-containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short-term combination regimen that has promising activity against malignant germ cell tumors of the ovary.     

Bilateral ovarian involvement as the only manifestation of malignant lymphoma

A 16-year-old girl presented with a large pelvic mass. At laparotomy, bilateral ovarian tumors were disclosed and bilateral salpingo-oophorectomy was performed. No evidence of extra-ovarian disease was found. Histopathological examination and histochemical immunoperoxidase studies demonstrated the tumors to be malignant lymphoma of the lymphoblastic type. The patient had radiotherapy and systemic chemotherapy and more than 10 years later she is alive with no evidence of recurrent disease. The rarity of ovarian involvement as the initial manifestation of malignant lymphoma is discussed. The question of whether this patient represents a case of a primary ovarian malignant lymphoma or merely represents a case of ovarian initial manifestation of an occult generalized disease cannot be answered.     

Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?

BACKGROUND: Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. METHODS: Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. RESULTS: Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. CONCLUSIONS: Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.     

A prospective trial of postoperative vaginal radium/cesium for grade 1-2 less than 50% myometrial invasion and pelvic radiation therapy for grade 3 or deep myometrial invasion in surgical stage I endometrial adenocarcinoma

A prospective trial was performed to evaluate the recurrence rate and 5-year disease-free survival rate in patients with surgical Stage I endometrial adenocarcinoma. Patients with Stage I, Grade 1 or 2 disease, less than 50% myometrial invasion, and no evidence of disease outside the corpus of the uterus were treated by hysterectomy and bilateral salpingo-oophorectomy and postoperative vaginal radium/cesium (Group 1). Patients with surgical Stage I, Grade 3 disease or deep myometrial invasion, and histologically negative paraaortic lymph nodes were treated with postoperative pelvic radiation therapy (5000-5040 cGY) (Group 2). Patients with malignant peritoneal cytologic findings also received progesterone therapy. Of the 92 Group 1 patients, there have been no recurrences and the 5-year estimated disease-free survival rate was 99%. Of the 41 Group 2 patients, there have been four (9.7%) recurrences but only one (2.4%) within the treated field (pelvis), and the 5-year estimated disease-free survival rate was 88%. Of the 133 patients, the 5-year estimated disease-free survival rate was 96%, and only one patient (0.7%) had a local pelvic recurrence. Of the 16 patients with malignant peritoneal cytologic findings who were treated with progesterone therapy, none has had a recurrence.     

子宫内膜间质肿瘤——附10例临床病理分析

 本文报道自1958年至1988年底于中国医学科学院肿瘤医院治疗的有完整临床及病理资料的10例子宫内膜间质肉瘤。参照组织学分类标准,10例均属于淋巴管内间质异位症(低度恶性子宫内膜间质肉瘤)。发病年龄平均为40.5岁。临床分期为Ⅰ期8例,Ⅱ期1例,Ⅲ期1例,其中Ⅰ期4例,Ⅱ期1例于术中发现肿瘤已播散至子宫以外。10例中8例行全子宫及救附件切除术,1例行全子宫单侧附件切除术,1例于外院手术仅行子宫次全切除术。术前辅以腔内治疗者2例,术后盆腔体外放疗6例,均达放射治疗剂量,术后化疗2例。10例中有2例复发,其中1例治疗后13年复发,经化疗后稳定,于复发后2年仍存活。1例于术后4年复发,经放射治疗后稳定,复发后6年仍存活。其中5例随访达5年以上,其5年及10年存活率均达100%。     

Benign and borderline clear cell adenofibromas of the ovary

The criteria for the diagnosis of benign and borderline clear cell adenofibromas and their biologic behavior were investigated by examination of the clinical and pathologic features of 18 tumors in these categories. Three tumors that showed no significant epithelial atypicality were classified as benign. Twelve tumors that contained glands or small solid nests composed of epithelial cells with nuclear characteristics of low-grade malignancy without invasion of the stromal component of the tumor were designated as borderline. Three predominantly borderline tumors with focal microinvasion of the stromal component were also studied. The 17 patients had nonspecific complaints. Sixteen of the tumors were unilateral without surface involvement; one patient had bilateral borderline tumors. Most of the women were treated by hysterectomy and bilateral salpingo-oophorectomy. Follow-up information was available for 16 of the 17 patients. No recurrences or deaths from tumor occurred in 14 patients (2 benign, 10 borderline, 2 microinvasive). One patient with a borderline adenofibroma had questionable lung metastasis 4 years after presentation, and another patient who had a microinvasive tumor had a pelvic recurrence 3.3 years postoperatively.     

Extraordinarily Prolonged Disease Recurrence in a Granulosa Cell Tumor Patient

BACKGROUND: Granulosa cell tumors are rare sex cord stromal lesions that comprise approximately 3% of all ovarian neoplasms. The vast majority of granulosa cell tumors are considered indolent but in spite of aggressive management, delayed recurrence is of significant concern. CASE REPORT: We describe a case involving a 67-year-old woman who presented with abdominal pain, bloody stools, and mild nausea. Following a CT scan of the abdomen and pelvis, a 19-cm pelvic mass was identified. Her prior medical history included a hysterectomy for uterine fibroids 40 years ago and a bilateral salpingo-oophorectomy for a presumed granulosa cell tumor 20 years ago. Final pathology revealed granulosa cell tumor with small bowel mesentery involvement. The patient underwent surgical resection and adjuvant chemotherapy; she is currently doing well. CONCLUSION: Granulosa cell tumors are considered to be of low malignant potential but they have the capacity to recur, even several years following initial patient management. This case exemplifies the disease's capacity for prolonged recurrence and further accentuates the significance of long-term follow-up in these patients.     

Long-term follow-up in patients with bilateral testicular germ cell tumors: a report of ten cases

Several risk factors have been identified for the development of testicular germ cell tumors with history of a testicular tumor in the contralateral testis being one of the most important factors; the incidence of bilateral tumors in large series ranges from 2% to 5%. The aim of this study was to evaluate the results of long-term follow-up in patients with bilateral testicular germ cell tumors. In a series of 247 patients with testicular germ cell tumors treated at Kobe University Hospital between 1966 and 1995, 10 patients (4.0%) had bilateral testicular tumors. Clinicopathological data are presented for these 10 patients and the literature is reviewed. Of the 10 patients with bilateral tumors, 2 had a simultaneous bilateral tumor, and in the remaining 8 patients, the second tumor was diagnosed after an interval of 2 months to 16 years. All 10 patients were diagnosed as stage I or II in both the initial and secondary tumors. Five patients had identical histological findings in both tumors. Eight patients were free of disease after a median observation period of 13.5 years, and the remaining 2 patients died of metastatic disease. The present results are essentially consistent with previous studies analyzing the features of bilateral testicular germ cell tumors. Considering these findings, close clinical follow-up and patient education appeared to be an appropriate follow-up strategy in patients with testicular tumors, as the secondary tumors can generally be cured with current treatment regimens. Received: August 7, 1998 / Accepted: January 5, 1999     

Systematic irradiation of the vaginal vault in stage I endometrial carcinoma

One hundred and twenty patients with clinical pathological stage I carcinoma of the endometrium were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and either pre- or postoperative intracavitary cesium insertion. External pelvic irradiation (45-50 Gy in 5 weeks) was given postoperatively in 36 cases, mainly for deep myometrial invasion. All the women have been followed for a minimum of 5 years. The overall 5-year survival rate is 86%. According to histological grading, the 5-year survival was 88, 83 and 57% for grades 1 (90 patients), 2 (23 patients) and 3 (7 patients) respectively. A total of 17 local and distant failures were observed: 10 patients had distant metastases, six patients had a pelvic failure and one had both. There was only one isolated vaginal recurrence. Depth of myometrial invasion was not a statistically significant indicator of outcome. Survival rates were comparable in pre- and postoperatively treated patients.     

Prognostic factors and treatment modalities in uterine sarcoma

The aim of this study was to identify the impact of various prognostic factors in the management of uterine sarcoma. Fifty-nine patients with uterine sarcoma were treated at King Faisal Specialist Hospital and Research Center between 1980 and 1997. Forty-three patients (73%) were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, 7 (12%) total abdominal hysterectomy and bilateral salpingo-oophorectomy with sampling of pelvic lymph nodes, and 9 (15%) had biopsy only. Nine patients received adjuvant treatment; five had radiation therapy (XRT), two had chemotherapy, one had combined XRT and chemotherapy, and one received hormonal treatment. Leiomyosarcoma cases accounted for 42% of all the uterine sarcomas, carcinosarcoma cases for 34%, and endometrial stromal sarcoma (ESS) for 24%. Fifty (85%) patients had pathologic grade II and III tumor, with only 9 patients grade I. Twenty-seven patients (46%) were classified surgically as stage I, 7 (12%) as stage II, 17 (29%) as stage III, and 8 (13%) had stage IV tumor. Recurrences developed in 34 patients (71%). The 5- and 10-year overall actuarial survival for all patients was 42%, and the corresponding relapse-free survivals for those who achieved complete response after primary treatment (48 patients) were 27% and 20%. On the univariate analysis, grade I tumors (p = 0.04), ESS (p = 0.02), nonmetastatic stage (p = 0.05), and negative peritoneal cytology (p = 0.04) were associated with better overall survival. Factors associated     

Synchronous bilateral ureteral and renal pelvic carcinomas: incidence, etiology, treatment and outcome

BACKGROUND: Synchronous bilateral urothelial tumors of the upper urinary tract are very rare. The authors reported baseline and long-term follow-up data for all patients in western Sweden during a 28-year period. METHODS: The authors performed a clinical and histopathologic study of all patients in western Sweden who were diagnosed with a malignant neoplasm in the renal pelvis or ureter between 1971 and 1998. RESULTS: Of 936 patients, 15 (1.6%) had synchronous bilateral tumors. The incidence of such tumors decreased in each successive decade. Abuse of phenacetin-containing analgesics by patients also decreased during the study period, as did the incidence of renal papillary necrosis. The median age at diagnosis of bilateral tumors was 68 years, and 80% of the patients were male. Eleven patients had bilateral tumors of the renal pelvis, two had bilateral ureteral tumors, and two had tumors of the renal pelvis and contralateral ureter. Partial renal pelvic, ureteral, or kidney resection on at least one side was possible in eight patients, and four patients were left untreated on at least one side. Only three patients underwent bilateral nephroureterectomy. Twelve patients (80%) had bladder carcinoma diagnosed either before or after diagnosis of the upper tract tumors. The median survival period for the 11 patients who received surgery for their bilateral tumors was 84 months. CONCLUSIONS: The decreasing incidence of synchronous bilateral upper tract tumors may be related to the prohibition of phenacetin-containing analgesics in the 1960s. Partial resection with preservation of the renal parenchyma was possible in the majority of patients. Survival for patients with bilateral tumors did not differ from that of patients with unilateral tumors.     

卵巢恶性生殖细胞肿瘤的治疗

探讨改进卵巢恶性生殖细胞肿瘤的治疗方法。方法 回顾分析我院收治的２３３例卵巢恶性生殖细胞肿瘤,Ｉ期９４例,Ⅱ－Ⅳ期４３例,复发转移９６例。单附件或全宫双附件加大网膜阑尾切除分别为７８例和１５１例,活检４例,单纯手术１７例,手术加放疗和化疗６５例,手术加化疗１５１例。结果全组存活１２７例,Ⅰ期存活７８例,Ⅱ－Ⅳ期１７例,复发转移３２例。     

28例Ⅰ期卵巢恶性生殖细胞肿瘤的治疗分析

28例1期卵巢恶性生殖细胞肿瘤中,13例作瘤侧附件切除,15例作双侧附件全子宫切除,术后均加化疗。全组五年生存率85.71％,瘤侧附件切除为84.6％,双侧附件全子宫切除为86.67％(P>0.05)。作瘤侧附件切除的13例中,2例复发死亡,2例复发后再次切除子宫卵巢加化疗后健在,9例成功地保留了正常卵巢及子宫。3例已结婚,并均正常分娩1次。本文着重讨论保留生育功能问题。     

Radical excision of malignant sacral tumors using a modified threadwire saw

BACKGROUND: Surgical treatment of malignant sacral tumors is difficult, and has a high rate of recurrence. OBJECTIVES: The aim of this study was to examine the wide margin of large and small malignant sacral tumors using a threadwire saw (T-saw). MATERIALS AND METHODS: We devised a flexible silver guide probe connected to a modified threadwire saw by a suture thread to perform osteotomies. We operated on 10 patients with sacral tumors using this device. The sacral excisions were performed via a posterior approach by four surgeons (two on each side) working simultaneously. RESULTS: We obtained a wide margin in all cases and no recurrence, after a mean follow-up of 4 years 2 months (range, 1 year 8 months-7 years 8 months). In one case, one nerve root on the right side was injured. CONCLUSIONS: Our new method is easier and faster than the conventional method in cases in which bilateral sacral nerve root canals require sectioning, and it produces a wide tumor margin.     

子宫平滑肌肉瘤：附11例临床病理分析

Eleven patients with leiomyosarcoma of the uterus are analysed clinicopathologically. The youngest patient was 36 and the oldest was 61 with a mean of 50.8 years. The common clinical symptoms were menorrhagia or irregular vaginal bleeding, lower abdominal pain and rapidly enlarging abdominal mass. None was diagnosed before operation for lack of specific symptoms. All tumors with 10 or more mitotic figures (MF) per 10 high-power fields (HPF) were diagnosed as malignant whereas for those with less than 10 MF/10 HPF the diagnosis of uterine leiomyosarcoma must depend on cellular pleomorphism, number of giant cells, increase in nuclear-cytoplasmic ratio and presence or absence of boundary between the tumor and normal tissue. The main treatment was total hysterectomy and bilateral salpingo-oophorectomy. The 2- and 5-year survival rates were 36.3% and 27.3%, respectively. Five cases with Stage III and IV lesions died within 11 months after operation. The clinical stage at the initial treatment is the most important prognostic factor. For tumors confined to the uterus, cellular pleomorphism, mitotic figure and boundary between the tumor and normal tissue are the other important prognostic factors.     

卵巢成熟畸胎瘤恶变的预后规律

目的：探讨卵巢成熟畸胎瘤恶变的生物学特性及预后规律。方法：对１８例卵巢成熟畸胎瘤恶变的生存率、平均缓解时间、复发转移规律及预后影响因素进行分析,以同期治疗的３５例卵巢未成熟胎瘤作对照。结果：卵巢成熟畸胎瘤恶变的中位发病年龄较未成熟畸胎瘤晚１０年,３、５、１０年生存率较卵巢未成熟畸胎瘤低（Ｐ＜０．０５）,术后复发转移率较卵巢未成熟畸胎瘤高（Ｐ＜０．０５）,术后平均缓解时间较未成熟畸胎瘤短（Ｐ＜０．０