Modified VAB-3 combination chemotherapy of stage IV endodermal sinus tumor of the ovary

A case of pure endodermal sinus tumor (EST) of the ovary with huge multiple liver metastases was treated with modified VAB-3 protocol. Serum alpha-fetoprotein (AFP) before treatment was 137,775 ng/ml. A complete clinical response was achieved with rapid shrinkage of liver metastases and normalization of serum AFP. Second-look laparotomy preformed 17 months after the start of chemotherapy revealed no evidence of disease. VAB-3 combination chemotherapy, which was proved to be very effective in the treatment of metastatic testicular cancer, also seems to be effective in the treatment of advanced EST of the ovary. This is believed to be the first detailed report of the successful management of advanced EST of the ovary.     

Primary endodermal sinus tumor of the endometrium. A clinicopathologic, immunocytochemical, and ultrastructural study.

We report a case of primary endodermal sinus tumor (EST) of the endometrium in a 42-year-old female. Although numerous extragonadal EST have been reported, primary EST of the endometrium is exceedingly rare. To our knowledge this is the fourth documented case of this nature. The tumor had the typical microscopic features of EST, with papillary, tubular, reticular, and solid growth patterns; occasional Schiller-Duval bodies and many intracellular and extracellular periodic-acid Schiff positive hyaline globules were seen. The neoplastic cells stained positively for alpha-fetoprotein (AFP), alpha-1-antitrypsin (A1AT), cytokeratin, and placental alkaline phosphatase. The globules were positive for AFP, A1AT, albumin, transferrin, and fibronectin. The tumor cells were negative for type IV collagen and the beta subunit of human chorionic gonadotropin (B hcG). Electron microscopic examination showed intracellular and extracellular basement membrane-like material, intracytoplasmic lumina with microvilli, and glycogen. The patient was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by four cycles of adjunct chemotherapy (vinblastine, bleomycin, and cisplatinum) repeated every 3 weeks. The serum AFP level was elevated significantly before the surgery and the tumor response was monitored by serial determination of serum AFP level. There was no evidence of recurrence 24 months after surgery.     

Yolk sac tumours of the ovary: an update.

AIMS: Yolk sac tumours of the ovary (YST), also called endodermal sinus tumours (EST) are rare and highly malignant tumours of utmost importance occurring in children and young adults. In the past, outcome was very poor and the disease was almost always fatal. With the refinement of chemotherapeutic regimens in the last several decades, survival rates have improved dramatically and fertility preserving surgery has become possible. The aim of this review is to provide the reader with an analysis of the available literature and a rational approach to patient management. METHODS: We performed a literature search in the PubMed database and the reference lists of relevant articles concerning yolk sac tumours of the ovary. FINDINGS AND CONCLUSION: There are no randomised studies relating to the management of YST of the ovary. The available literature is composed of retrospective reviews and case reports that span several decades. Prognosis nowadays is good in stage I and II but still comparable to that of ovarian epithelial cancer in stage III and IV. The overall good prognosis is due to the fact that most of ovarian YST are diagnosed at an early stage where 5years survival reaches 95%. Appropriate surgical treatment for patients where fertility needs to be preserved consists in laparotomy with unilateral salpingo-oophorectomy, peritoneal cytologic studies, omentectomy, multiple peritoneal and abdominal biopsies and resection of all visible disease. Three courses of BEP (bleomycin, etoposide, cisplatin) is the current standard therapy and four courses is recommended in case of bulky residual disease after surgery. Serum alpha-feto-protein (AFP) is a useful marker for the diagnosis and management of YST.     

An early combined endodermal sinus tumor of the ovary that was diagnosed due to torsion of serous cystadenoma--a case report

Reported is a rare case of a 2.5cm endodermal sinus tumor (EST) that was included within a 11 x 10.5 cm serous cystadenoma. A 24-year-old female suddenly complained of abdominal pain caused by having undergone an intestinal torsion of a left ovarian tumor. After a unilateral salpingo-oophorectomy the serum AFP was 219.8 ng/ml. The patient then received two cycles of cis-platinum, vinblastine and bleomycin combination chemotherapy. After one cycle, the serum AFP decreased to a normal level and the woman has remained free of disease 6 months after the discovery of her tumor. In this case, fortunately, this torsion of a serous cystadenoma enabled us to find the EST at a very early stage.     

Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary.

Serum AFP was determined serially by radioimmunoassay in 13 patients with ovarian germ cell tumors and in one patient with bilateral pure gonadoblastoma. There were 4 patients with pure dysgerminoma, one with pure endodermal sinus tumor (EST) and 8 with mixed germ cell tumors, all containing EST. The patients with dysgerminoma and gonadoblastoma had normal serum AFP at all times. All patients with tumors containing EST had raised serum AFP, although in most cases it was first determined between 1 and 3 weeks after operation and there was no evidence of metastases. Serum AFP became normal 5 to 7 weeks after operation and began to rise when disease recurred. Serum AFP determinations detected presence of recurrent disease long before it became detectable by other methods. Serum CEA was determined serially by radioimmunoassay in 8 of these patients, including 2 who dies with metastases, and was normal on all occasions.     

Endodermal sinus tumor and mucinous cystadenofibroma of the ovary. Occurrence in an 82-year-old woman

We encountered an unusual ovarian tumor consisting of a mixture of typical endodermal sinus tumor (EST) and mucinous cystadenofibroma that occurred in the ovary of an 82-year-old female patient. The EST component showed the classic histologic features of this tumor. Serum alpha-fetoprotein (AFP) level was not determined. Tumor stains were negative for AFP but positive for alpha-1-antitrypsin. The malignant germ cell component was intimately associated with the benign mucinous component. Focal production of epithelial mucin and carcinoembryonic antigen (CEA) in the EST component suggested a probable association between the two tumor types. The tumor was confined to one ovary, and the patient is disease-free 2 years after surgical therapy. This neoplasm is unique not only for the malignant germ cell component occurring in an 82-year-old woman, but for the unusual combination of tumor types. The pathogenesis is unknown.     

AFP-producing gastric carcinoma: multivariate analysis of prognostic factors in 270 patients

Serum alpha-fetoprotein (AFP) is sometimes high in patients with primary gastric carcinoma, and there is no comprehensive study on the clinicopathologic characteristics and prognostic factors of AFP-producing gastric carcinoma (AGC). To clarify the variables associated with the survival after gastrectomy for AGC, we reviewed the data of patients with AGC and examined the independent prognostic factors. We studied 270 cases of AGC reported in the Japanese literature from June 1982 to March 2001, together with 1 patient of our own experience. The clinicopathologic findings, including serum AFP level, operative curability, and stage of the disease were examined, and factors associated with survival were determined by multivariate analysis. There were 15 stage I tumors (6%), 50 stage II tumors (19%), 51 stage III tumors (20%), and 145 stage IV tumors (55%). The tumors were characterized by frequent serosal invasion (75%), lymph node metastasis (83%), liver metastasis (33%), stage III or IV disease (75%), and noncurative operation (48%). The survival was influenced by the serum AFP level, tumor size, serosal invasion, lymph node metastasis, and liver metastasis, but the independent prognostic factors were operative curability (curative vs. noncurative) and stage of the disease (I, II vs. III, IV). Although the 5-year survival rate and median survival period in all patients were 22% and 14 months, respectively, those in patients with curative gastrectomy were 42% and 29 months, respectively. The results indicate that operative curability and stage of the disease are factors associated with the survival of patients with AGC. Although tumors are often advanced and complicated with liver metastases, long-term survival can be achieved when patients with stage I or II tumor undergo curative gastrectomy.     

An analysis of prognostic factors in stage III and IV Hodgkin's disease treated at a single centre with MVPP.

Two hundred and twenty seven patients with stage IIIA-IVB Hodgkin's disease have been treated at a single centre with MVPP chemotherapy followed by radiotherapy to sites of previously bulk disease. The median follow up is 58 months. 119 patients (52%) had stage IV disease. Overall complete remission (CR) rate was 72%. Discriminant analysis of factors predictive for complete remission showed that low albumin was the only independent factor that predicted a significantly lower chance of CR. Overall five year survival was 73%. A Cox multivariate analysis demonstrated that age greater than 40 years, stage IV disease, presence of bulk disease, low serum IgG and male sex to be variables which independently predicted poorer prognosis in terms of overall survival. Stage IV and lymphocyte depleted or unclassified histologies were independently predictive for poorer progression-free survival. Patient weight greater than 70 kg and stage IV disease were adverse prognostic factors for relapse free survival. Results are compared to other published multivariate analyses of prognostic factors in advanced Hodgkin's disease.     

Evaluation of five tumor markers (AFP, CEA, hCG, hPL and SP1) in monitoring therapy and follow-up of patients with testicular germ cell tumors

61 patients with seminoma and 113 with nonseminomatous germ cell tumors of the testis were treated according to the histology, stage of disease, and serum levels of tumor markers (CEA, AFP, hCG, hPL and SP1). 33 were stage I, 63 stage II, and 78 stage III patients. Most patients with seminoma, mature teratoma, immature teratoma, and 'pure type' embryonal carcinoma, as well as the latter three types with seminomatous admixture, had normal serum levels of the markers. Sometimes, slightly elevated levels of hCG suggested the presence of metastases. But, serial measurements of the markers were seldom useful in monitoring therapy. The 5-year tumor-free survival rates were favorable: 100% for stage I and II disease; and 57 or 44% for, respectively, stage III seminoma or the other tumors amounting to 10% of the nonseminomatous group. The role of the five markers was significant in patients with teratoma with malignant transformation, choriocarcinoma, endodermal sinus tumor (EST), and embryonal carcinoma or teratocarcinoma with an admixture of EST or choriocarcinoma or both. Elevation of a marker was a grave prognostic sign. The 5-year survival rates were 100, 16, and 4% for stages I, II and III disease, respectively. An elevated level of one or more of the markers assayed was always useful for monitoring therapy. Decreasing level indicated regression. However, return of an elevated level to normal did not indicate eradication of all tumor and called for diagnosis by imaging modalities. Constantly elevated or increasing marker levels during treatment indicated resistance to therapy. An increasing level from any nadir during remission indicated recurrence. Elevated levels of any of the five markers tested were as important as imaging modalities, and often more sensitive.     

Endodermal sinus (yolk sac) tumor elements in testicular germ-cell tumors in adults: comparison of prospective and retrospective studies

The incidence of endodermal sinus tumor (EST) or yolk sac tumor (YST) elements has been studied in two series of testicular germ-cell neoplasms in adults. One series, consisting of 200 germ-cell neoplasms seen from 1053 through 1968, was studied retrospectively, and the other, consisting of 147 cases seen from May 1974 through February 1979, was studied prospectively. Excluding the cases of pure seminoma, EST(YST) elements were found in 21 (28.7%) of 73 cases in the retrospective series and in 27 (44.4%) of 61 cases in the prospective series. The EST(YST) elements were in all cases admixed with other neoplastic germ-cell elements and varied from microscopic foci to being the predominant element within a tumor. The EST(YST) elements were histologically similar to infantile EST(YST) and EST(YST) in other locations. Serum alphafetoprotein (AFP) was determined in the majority of patients in the prospective series, and there was good correlation between the presence of EST(YST) elements within the tumor and elevated levels of AFP. The results of the present study indicate that EST(YST) elements occur quite frequently in testicular germ-cell neoplasms in adults and provide an explanation for the raised levels of serum AFP found in many adults with testicular germ-cell tumors. The results emphasize the importance of a thorough and careful pathologic examination of testicular germ-cell tumors, and the value of AFP as a tumor marker in patients with EST(YST). The results also lend further support to the view that EST(YST) elements found in testicular germ-cell tumors in adults are homologous with infantile EST(YST) and that EST(YST) is a distinctive and specific type of germ-cell neoplasm and should be included as such in the classification of testicular tumors.     

Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma

Serum concentrations of angiogenic factors have been reported to correlate with tumour burden and prognosis in metastatic melanoma. The present study was performed to assess the value of angiogenic factors in serum in indicating response or failure to chemotherapy and immunochemotherapy in stage IV melanoma. Thirty-five patients suffering from stage IV melanoma according to the American Joint Committee on Cancer (AJCC) criteria were included in this prospective study. Before and following chemotherapy or immunochemotherapy, serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-AB), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) were measured. Staging examinations following chemotherapy revealed 15 patients with response to therapy (complete response, partial response, stable disease), 14 patients with progressive disease and six patients with mixed response. Patients who responded to therapy showed a significant decrease in the serum level of IL-8 at the time of staging examinations, whereas patients with progressive disease did not. Following chemotherapy, serum concentrations of PDGF-AB had significantly decreased in both patients with response and patients with progressive disease. Comparing the VEGF and bFGF levels of responders and non-responders after a single administration of cytostatics showed significantly lower concentrations in patients with response to therapy. In all patients, a high intra- and inter-individual variability of serum values was observed during application of therapy. It can be concluded that low IL-8 serum levels after chemotherapy indicate response to chemotherapy in stage IV melanoma patients. The persistence of elevated serum levels of VEGF and bFGF following the initial cytostatic administration may help to identify patients resistant to chemotherapy. The distinct variability of serum levels indicates that processes other than tumour angiogenesis also influence the serum concentration of the examined angiogenic factors.     

Ovarian and extragonadal malignant germ-cell tumors in females: A single-institution experience with 43 patients

From 1978 to 1992, 276 patients (pts) with MGCT were treatedin our institution. Forty-three of the pts were female (15,5%).Median age at diagnosis was 20 years (newborn-70). Histologywas dysgerminoma (D) in 14 pts (including 2 anaplastic D), endodermalsinus tumor (EST) in 9 pts, immature teratoma in 10 pts andmixed tumors in 10 pts. Primary locations were as follows: ovary(O) 33 pts and extragonadal (EG) 10 pts (pineal in 4 cases,mediastinum in 3, sacrum in 2 and pharynx in 1). Stage: I in20 (16 0 , 4 EG), U in 7 (5 O, 2 EG), IE in 12 (10 O, 2 EG)and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminomapts, HCG in only 5 pts and LDH in 15/36 pts. TREATMENT RESULTS:OVARIAN TUMORS: all but one pt (biopsy only) underwent surgery: unilateral oophorectomywas performed in 15 pts and bilateral oophorectomy (+/–hysterectomy, + / – others) in 17 pts. Fourteen pts wererendered disease-free, 8 pts had residua] tumor (RT) ±2cm and 11 RT >2 cm. Chemotherapy (PVB or BEP) was given to28 pts, radiotherapy to 2 pts and no additional treatment to3. Finally, 30 pts achieved complete response (CR) and nonehave relapsed at a median follow-up of 43 months. EG tumors:None of the pts underwent radical surgery. Radiotherapy wasapplied to 4 pineal tumors and BEP or PVB were given to all10 pts. To date 6 pts are disease-free, 1 is alive with matureteratoma, 2 are alive with disease and 1 died of toxic effects.The projected overall survival of the series as a whole is 89%at 10 years, and it is significantly higher for pts withoutEST (p ± 0.02) and for pts with AFp ±1000 (p ±0.01) and age ± 22 years at diagnosis (p ± 0.01).The projected event-free survival at 10 years is 80.4% (87.7%for ovarian rumors vs. 54% for extragonadal, p = 0.05). No eventswere recorded after 28 months. CONCLUSIONS: The present results reflect the dramatic effectiveness of cisplatin-basedchemotherapy for ovarian MGCT and confirm that unilateral oophorectomycan preserve fertility without compromising cure. Age >22years, histology (EST) and serum AFP > 1000 ng/ml are possibleprognostic factors (univariate analysis) to be tested in anindependent body of data on cisplatin-treated patients. germ-cell tumors, ovary, extragonadal, females, cisplatin, toxicity, prognosis     

Prolonged Survival of Stage IV Malignant Mixed Müllerian Tumor of the Ovary after Carboplatin,Mesna, Ifosfamide,and Cis-Platin Chemotherapy: Case Report

Abstract

Malignant mixed müllerian tumors (MMMT) of the ovary are rare, aggressive and rapidly progressive tumors. According to the available literature, the presence of metastatic disease rarely permits long term survival. We report on a 64-year old patient with stage IV ovarian MMMT who achieved a surgically-documented complete response (CR) after 6 cycles of carboplatin, mesna, ifosfamide, cis-platin. Pelvic recurrence was diagnosed 14 months later; the patient received 6 cycles of the same regimen used as first-line chemotherapy which resulted in a second complete response lasting for 4 months. The patient died 37 months after initial diagnosis due to intestinal occlusion. In the current case Ca 125 was significantly increased at clinical presentation of disease but not at the time of recurrence.     

Clinical Efficacy and Prognosis Factors for Advanced Hepatoblastoma in Children: A 6-year Retrospective Study

Objective: This study aimed to investigate the effect of multimodality treatment of advanced paediatrichepatoblastoma (HB) and the factors affecting prognosis. Methods: A total of 35 children underwent multimodalitytreatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stemcell transplantation. The patients were followed up every month. Results: Serum AFP levels in 33 out of 35patients in this study were significantly increased (P = 0.0002). According to the statistical scatter plot, the valuesof serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318 ng/dl, respectively. Of the35 cases, 21 were stage IV. 18 cases were treated with systemic chemotherapy before surgery, and 3 cases withlocally interventional chemotherapy before surgery. Statistical analysis showed that the preferred interventionaltreatment affected prognosis, and that there was a statistically significant difference (P = 0.024). Some 33patients completed the follow-up, of which 17 were in complete remission (CR), 5 were in partial remission(PR), 1 became disease progressive (DP) , and 10 died. The remission and overall survival rates were 66.7%(22/33) and 69.7% (23/33), respectively. Patients with the mixed HB phenotypes had worse prognoses than theepithelial phenotype (P < 0.001), and patients in stage IV had a lower survival rate than those in stage III (P <0.001). Conclusion: Multimodality treatment can effectively improve remission rate and prolong the survival ofchildren with advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver malignant tumors,HB pathological classification, and staging are highly useful in predicting prognosis.     

Endodermal sinus tumor of the ovary and alpha fetoprotein: a case report.

Yolk sac tumors of the ovary are associated with elevations in serum levels of alpha fetoprotein (AFP). Thus, an antigenic marker is provided for evaluating therapeutic results in selected patients. A patient with a pure endodermal sinus tumor of the ovary is presented who underwent serial determinations of AFP. The effectiveness and limitations of serial AFP levels as demonstrated by this case are discussed in addition to the surgical and chemotherapeutic management of patients with yolk sac tumor of the ovary.     

Successful treatment of pure endodermal sinus tumors in adult men

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.     

Growing teratoma syndrome in a post laparoscopic excision of ovarian immature teratoma

A 26-year-old girl was referred to us in December 2008 with progressive pelvic mass while on chemotherapy. In May 2008, she presented with large adnexal mass and high alpha-fetoprotein (AFP, 265.7 ng/mL; normal range, 0 to 10). She underwent laparoscopic right salpingo-oophorectomy with staging. Since histology was immature teratoma grade I, FIGO stage 1 she was kept on surveillance. In September 2008, she developed recurrent pelvic mass with AFP levels of 2,400 ng/mL. Three courses of chemotherapy (bleomycin-etoposide-cisplatin) were given. Post-chemotherapy AFP normalized but tumor size increased. CT-scan (abdomen-pelvis) showed a large pelvic mass with calcification specks; infiltrating the sigmoid colon and abdominal wall. With provisional diagnosis of growing teratoma syndrome she had exploratory laparotomy with excision of pelvic mass along with sigmoid colon, excision of right pelvic and subcutaneous deposits, omentectomy and sigmoid anastomosis. Left ovary, left tube and uterus appeared normal and were preserved. Histology of all masses showed mature teratoma, no immature elements. At six months follow up she is disease free and has resumed menstruation. Growing teratoma syndrome is a clinico-pathological presentation during/post-chemotherapy in malignant ovarian germ cell tumor where mature teratoma grows and requires complete surgical excision. Our case highlights the safety and adequacy concerns of laparoscopic management of malignant ovarian tumor. Literature review suggests good prospects of resumption of menses, child bearing and five year survival in case of growing teratoma syndrome.     

Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254 patients with complete surgical staging

A retrospective analysis was performed to evaluate the clinical characteristics and prognostic factors in the patients with clear cell carcinoma (CCC) of the ovary. After central pathological review and scanning of the medical records of nine Japanese institutions between 1992 and 2003, a total of 254 patients with CCC of the ovary were enrolled in the present study. Mean age was 52.4 years (range 23-73 years). Tumours were 13% (33/254) stage Ia, 36% (92/254) stage Ic, 13% (33/254) stage II, 30% (80/254) stage III, and 6% (16/254) stage IV. Five-year progression-free survival and overall survival was 84 and 88% in stage I, 57 and 70% in stage II, 25 and 33% in stage III and 0 and 0% in stage IV, respectively. Retroperitoneal lymph node metastasis was observed in 9% in pT1a tumours, 7% in pT1c tumours, 13% in pT2 tumours, and 58% in pT3 tumours, respectively. There was no survival benefit according to chemotherapeutic differences in the patients who received complete surgical staging procedures and conventional chemotherapy. Peritoneal cytological status was an independent prognostic factor in stage Ic patients (P=0.03) and only residual tumour diameter was an independent prognostic factor in stage III, IV patients (P=0.02). Our results suggest that cytoreductive surgery resulting in no residual tumour only could improve the prognosis of advanced CCC patients.     

Prognostic value of tumor marker determinations in testicular cancer patients

This report is based on the observation of 109 patients with testicular cancer over a period of 6 years. At the time of orchiectomy metastases were present in 54 patients. In 13 patients with an initially nonmetastatic disease, secondaries occurred later. The aim of this study was to evaluate the role of serum levels of human chorionic gonadotropin (beta-HCG) and alpha-fetoprotein (AFP) in the prognosis for achieving a complete remission. The importance of serial serum AFP and beta-HCG determinations for the early detection of tumor metastases was also evaluated. Remission rates were lowered significantly in patients with serum AFP levels above 500 micrograms/liter (8%, P less than 0.0005) and serum beta-HCG concentrations exceeding 5,000 U/liter (27%, P less than 0.05). For an early detection of metastases the best results (efficiency 0.92) were achieved with the combination of beta-HCG with AFP and X-ray examination of the chest.