Uterine Papillary Serous Carcinoma Treated with Intraperitoneal Cisplatin and Intravenous Doxorubicin and Cyclophosphamide

This study was designed to evaluate the efficacy of intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide in patients with uterine papillary serous carcinoma. Sixteen patients with uterine papillary serous carcinoma underwent complete surgical staging and placement of an intraperitoneal port. Postoperatively, they received cisplatin (100 mg/m²) given intraperitoneally and doxorubicin (50 mg/m²) intravenously and cyclophosphamide (600 mg/m²) intravenously every 4 weeks for 6 cycles. The intraperitoneal ports did not function in 3 patients immediately following surgery. The remaining 13 patients constitute the study group. The patients ranged in age from 37 to 77 years. There were 1 patient with Stage IA, 3 with Stage IB, 2 with Stage IIB, 2 with Stage IIIA, 2 with Stage IIIC, 1 with Stage IVA, and 2 with Stage IVB. At the end of surgery no gross residual disease remained except for 1 patient who had less than 1-cm nodules in the peritoneal cavity. Eleven of the patients underwent 6 cycles of chemotherapy, 1 patient underwent 3 cycles, and 1 patient underwent 1 cycle. A total of 71 cycles of chemotherapy were given. All patients developed alopecia. Two patients developed neutropenic fever; one was treated with antibiotics, the other patient died from urosepsis. One patient had a >15% decrease in left ventricular ejection fraction which led to a dose reduction of doxorubicin. One patient had a urinary tract infection and one patient developed a port infection which necessitated its removal. Seven patients have died, 1 is alive with disease, and 5 patients are alive with no evidence of disease. Five of the 7 patients with extrauterine disease have died of disease. One is alive with disease and the other is free of disease. The median survival of these patients was 34 months with an overall 3 years survival of only 24.1%. Although the protocol was reasonably well tolerated, the overall survival did not differ from that of a similar group of patients treated at our institution with intravenous chemotherapy. There was a high incidence of dysfunction of the intraperitoneal ports (25%). This approach with intraperitoneal cisplatin presents no therapeutic advantage for these patients.     

Influence of Postoperative Treatment on Survival in Patients with Uterine Papillary Serous Carcinoma

Background.Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis.Methods.Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated.Results.All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26.1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05).Conclusion.These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.     

子宫浆液性癌的诊治进展

子宫浆液性癌[USC,又称子宫乳头状浆液性癌（UPSC）],是非雌激素依赖性Ⅱ型子宫内膜癌的重要类型之一。其具有高度恶性的生物学特性：侵袭性强、术后复发率高,多灶性复发且病灶多位于盆腔以外的特点导致无法再用手术、放疗等方法进行挽救处理。因该病发病率不高,既往的小数据研究无法进行精细的分组统计,本文列举近年来多篇大数据回顾分析结果,并参照美国妇科肿瘤协会（SGO）与美国国立综合癌症网络（NCCN）对UPSC的治疗建议,介绍该病的临床特点,对不同FIGO分期的各种处理方式提供数据支持,旨在提高大家对该病的认识以掌握对该病的处理原则。     

子宫浆液性癌治疗现状与进展

子宫浆液性癌[USC,又称子宫乳头状浆液性癌(UPSC)]是一种Ⅱ型子宫内膜癌的特殊病理类型,具有侵袭性强、术后复发率高、易发生远处转移和预后较差等特点。由于该病发病率较低,缺少前瞻性随机对照试验,近年多篇大数据回顾分析结果结合美国国立综合癌症网络(NCCN)对USC 的治疗建议,推荐全面分期手术,术后辅以化疗、放疗、分子靶向治疗、免疫疗法等综合治疗。目前,关于USC 的最佳治疗方案尚未达成共识。现就USC 相关治疗现状和进展进行阐述,希望对临床治疗有一定的帮助。     

卵巢外腹膜浆液性乳头状癌研究进展

卵巢外腹膜浆液性乳头状癌是原发于腹膜,光镜下组织学形态同卵巢浆液性乳头状癌,而卵巢本身正常或仅浅表受累的一种恶性肿瘤,其临床表现主要为腹胀、腹痛和腹围增大等非特异性消化道症状,极易误诊为晚期卵巢癌,诊断时必须综合考虑术中情况和术后病理。该病的治疗原则以手术为主,不能彻底切除者行肿瘤细胞减灭术,术后辅以铂类为基础的联合化疗。随着对该病认识的加深及其临床诊治水平的提高,相关的病例报道也日渐增多。对近年来有关卵巢外腹膜浆液性乳头状癌的临床表现、诊断以及治疗的研究进展做一综述。     

Complete Response of a Stage IV Uterine Papillary Serous Carcinoma to Neoadjuvant Chemotherapy with Taxol and Carboplatin

Uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype of endometrial cancer. Currently, no effective chemotherapy regimens exist. We report a case of complete response of a stage IV UPSC to neoadjuvant chemotherapy with Taxol and carboplatin.     

Primary Peritoneal Serous Papillary Carcinoma: A Study of 25 Cases and Comparison with Stage III–IV Ovarian Papillary Serous Carcinoma

The clinical characteristics and treatment outcome of patients with primary peritoneal serous papillary carcinoma (PPSC) (n= 22) was compared with stage III–IV papillary serous ovarian carcinoma (PSOC) patients (n= 63). There were no statistically significant differences between the PPSC and PSOC patients with regard to the mean age, menopausal status, parity, ascites fluid volume, proportion of stage IV disease, and the rate of optimal debulking achieved. The median disease-free interval was 15 and 18 months; the median survival was 21 and 26 months; and the 5-year survival was 18 and 24% for the PPSC and PSOC groups, respectively. The median survival time for patients with a residual tumor ≥2 cm was 20.5 and 24 months, and for residual tumor <2 cm was 46 and 41 months, in PPSC and PSOC patients, respectively. Survival was thus better, in both groups, when residual disease at the end of the operation was <2 cm, though this was statistically significant only for PSOC (P< 0.02). We conclude that patients with PPSC should be treated as other stage II–IV PSOC patients. Combining optimal debulking with a platinum-based chemotherapy may offer the patient the most effective treatment.     

Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC).

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.     

Extraovarian Peritoneal Serous Papillary Carcinoma: A Case-Control Retrospective Comparison to Papillary Adenocarcinoma of the Ovary

Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further.     

Death Rate and Recurrence Pattern among 841 Clinical Stage I Endometrial Cancer Patients with Special Reference to Uterine Papillary Serous Carcinoma

Eight hundred thirty-nine clinical stage I endometrial carcinoma patients diagnosed between 1979 and 1988 were treated at the University Hospital in Linköping. Forty-two (5%) had uterine papillary serous carcinoma of which 52% died of their disease. The recurrence rate, defined as new evidence of disease 6 months or more after termination of the initial treatment, was 31% among the UPSC patients compared to 6% in the non-UPSC group. The site of recurrence also differed significantly between the two groups, with the abdomen as the most common site among UPSC patients (46%) and the vagina (34%) among the ordinary adenocarcinoma patients. All UPSC patients with recurrence died of their malignancy compared to 61% of the ordinary adenocarcinoma patients. Ninety percent of isolated vaginal recurrences in ordinary adenocarcinoma patients (17) were diagnosed at a scheduled outpatient checkup. Of these, 13 are alive with no known disease after treatment.     

子宫浆液性癌的分子学特征及靶向治疗研究进展

子宫浆液性癌（uterine serous carcinoma,USC）是一种特殊类型的子宫内膜癌。有别于常见的子宫内膜样腺癌,USC较为少见,且恶性程度高,侵袭转移风险高,临床上预后较差。随着子宫内膜癌分子学研究的不断深入,分子学特征被应用于子宫内膜癌的病理分型诊断、治疗和预后评价中。研究发现USC中存在多种基因的突变,这些相关基因的突变对该病的诊断和预后具有重要的指导意义。同时,特异性的分子学改变为USC的靶向治疗提供了潜在的治疗靶点。目前,多种靶向治疗手段包括人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）抑制剂、免疫检查点抑制剂、抗血管生成治疗、磷脂酰肌醇3激酶（phosphoinositide 3-kinases,PI3K）通路抑制剂和多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase,PARP]抑制剂等被应用于USC的临床治疗研究中,针对性的靶向治疗有望成为USC治疗的新突破。     

Papillary Serous Carcinoma of the Uterus: Increased Risk of Subsequent or Concurrent Development of Breast Carcinoma

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.     

Combined Chemotherapy Using Cisplatin, Ifosfamide and Bleomycin (PIB) in the Treatment of Advanced and Recurrent Cervical Carcinoma

Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.     

Genetic Alterations of the WT1 Gene in Papillary Serous Carcinoma of the Peritoneum

Objective. The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP.Methods. Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings.Results. Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors.Conclusions. Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors—not from inactivating gene mutation and subsequent allelic loss.     

子宫静脉内平滑肌瘤病的诊治进展

子宫静脉内平滑肌瘤病（intravenous leiomyomatosis,IVL）是一种罕见的疾病,可沿血管生长,延伸到下腔静脉,甚至心脏。目前对其发病机制尚有争议,多数学者考虑其起源于子宫肌瘤直接侵入子宫肌层静脉并沿血管腔扩散所致。子宫IVL好发于40～50岁有生育史的女性,早期临床表现不典型,如累及下腔静脉或右心时,可出现腹水、肝脾肿大、呼吸困难、心力衰竭,严重者甚至猝死。手术是目前首选的治疗方法,但具体的手术方案尚无统一共识。该病复发率高,术后需长期严密随访。综述子宫IVL的发病机制及高危因素、临床及影像学表现、诊断与鉴别诊断、治疗、预后及随访,以期为该病的诊疗提供参考。     

Epidemiologic and Surgicopathologic Findings of Papillary Serous and Clear Cell Endometrial Cancers When Compared to Endometrioid Carcinoma

PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.     

Combination Chemotherapy with Etoposide, Cisplatin, and Doxorubicin in Mixed Müllerian Tumors of the Adnexa

Eleven patients with ovarian (9) or fallopian tube (2) mixed müllerian tumors who underwent primary surgery at Yale New Haven Medical Center between 1986 and 1994 were treated with etoposide, cisplatin, and doxorubicin. Responses were observed in three (60%) of five evaluable patients with two complete (40%) and one partial (20%) response. Median survival time was 17 months with an estimated 3-year survival of 18%. Survival may have been improved with earlier stage disease, but survival was not significantly improved with optimal surgical cytoreduction in patients with advanced disease. Four patients required dose reductions for myelosuppression and there was one treatment related death. Toxicity was comparable to other combination chemotherapy regimens. EPA has modest therapeutic activity in ovarian and fallopian tube MMT.