Primitive Myxoid Mesenchymal Tumor of Infancy With Fatal Hemorrhage In Utero: A Case Report and Literature Review.

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare soft tissue sarcoma in childhood. We present the case of a newborn male who experienced a severe hemorrhage in utero from the tumor on the scalp. He died at the age of 24 hours owing to hemorrhagic shock. The tumor was posthumously diagnosed as PMMTI. A literature search indicated that cases of severe hemorrhage from soft tissue sarcomas in utero or at birth are limited to infantile fibrosarcoma. This is the first case of PMMTI with massive hemorrhage. Clinicians must be aware of hemorrhagic complications of PMMTI.

Metastatic choriocarcinoma successfully treated with paclitaxel and carboplatin after interstitial lung disease induced by EMA-CO.

BACKGROUND: Well-established first-line chemotherapy (such as EMA-CO) is extraordinary active for gestational choriocarcinoma. However, it causes very serious situation once drug-induced acute interstitial lung disease occurs during the treatment. CASE: A 31-year-old Japanese woman with metastatic choriocarcinoma was treated with EMA-CO as an initial chemotherapy regimen for seven cycles. Her beta-hCG dropped from 13,087 ng/ml to 2.2 ng/ml. At 11 days after 7th cycle of EMA-CO treatment, however, she developed respiratory failure, and was diagnosed as having EMA-CO-induced interstitial lung disease with bilateral ground-glass opacity on CT scan, and the examination of the bronchoalveolar lavage fluid. After high-dose steroid therapy, symptoms and ground-glass opacity on CT scan were remarkably improved. She then commenced a regimen of carboplatin (AUC 5) and paclitaxel (180 mg/m2). After completing 8 cycles, her beta-hCG dropped to <0.2 ng/ml. Three additional cycles were administered and the patient remained clinically free of disease, with normal beta-hCG levels for 11 months. CONCLUSIONS: Paclitaxel and carboplatin combination is active and appears to be a viable alternative to EMA-CO combination chemotherapy in metastatic choriocarcinoma even after EMA-CO-induced interstitial lung disease.

Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.

OBJECTIVE: To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation. METHODS: We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21. RESULTS: TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in 1 of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%). CONCLUSIONS: Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation.

Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma.

OBJECTIVE: The purpose of this study was to report the results of adjuvant CPT-11 and MMC combination chemotherapy (CPT-M) for ovarian clear cell adenocarcinoma (OCCA). METHODS: Between 1996 and 2002, 20 patients with OCCA underwent primary debulking surgery and received 6 treatments of CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2), 2 weeks apart with a space of 3-4 weeks between the 3rd and 4th treatment in adjuvant setting. Overall survival was compared with our historical control treated between 1983 and 1995, in which 14 patients with OCCA were treated with an initial optimal standard surgery and postoperative adjuvant cyclophosphamide, doxorubicin, and cisplatin (CAP) combination chemotherapy. RESULTS: Median age was 51 years old (range, 29-74). Twelve patients were in stage Ic, 1 in stage IIa, 5 in stage IIc, 1 in stage IIIc, and 1 in stage IV. Optimal cytoreduction with standard surgery was obtained in all 20 patients. The major toxicity with this regimen was neutropenia, which was reversible. The incidences of grade 3 and 4 neutropenia were 25% and 15%, respectively. The non-hematological toxicities were generally mild and well tolerated. One patient with stage Ic refused chemotherapy after the first cycle of CPT-M, and died of her disease 8 months after initial surgery. Five-year survival rate was 95.0% for CPT-M group, and 63.5% for CAP group (P = 0.042). Survival was significantly better for patients treated with CPT-M. CONCLUSION: This preliminary study shows that the combination of CPT-M appears to be safe and useful in patients with OCCA. Prospective randomized trials should be conducted to assess this regimen appropriate for women with OCCA.

Adjuvant chemotherapy as treatment of high-risk stage I and II endometrial cancer.

OBJECTIVE: This study was performed to define the subgroups of patients who benefit from postoperative adjuvant chemotherapy in stage I and II endometrial carcinoma. METHODS: A retrospective review of 170 International Federation of Gynecology and Obstetrics (FIGO) stage I and II endometrial carcinoma patients treated between 1988 and 2000 at Niigata University Hospital was performed. All patients underwent surgery, of which 41 patients underwent adjuvant chemotherapy, consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The patients were divided into low-risk and high-risk groups based on the number of prognostic factors (tumor grade G3, outer half myometrial invasion, lymph-vascular space involvement (LVSI), and cervical invasion). The 5-year disease-free survival and the 5-year overall survival for the low-risk group were 97.4%, and 100%, respectively, which were significantly better than 77.4% and 88.1% for the high-risk group (P < 0.0001, P < 0.0001), respectively. Among high-risk group patients, the 5-year disease-free survival and the 5-year overall survival were 88.5% and 95.2% in 26 patients treated with adjuvant chemotherapy, and 50.0% and 62.5% in eight cases who underwent only surgery (P = 0.0150, P = 0.0226). Disease recurrence occurred in 7 (20.6%) of 34 high-risk group patients. Four of seven recurrences occurred in patients who did not receive postoperative chemotherapy, in which all four were distant failure. In the remaining three patients who were in the CAP group, two had vaginal wall recurrence and only one had pulmonary recurrence. Three recurrences were also observed in the 133 low-risk group patients. Only isolated vaginal wall recurrence occurred in three patients without adjuvant chemotherapy after the initial surgery. CONCLUSIONS: There is possibility that postoperative adjuvant CAP may be omitted in surgical stage I or II endometrial cancer patients with 0 or 1 prognostic factor. The high-risk group of patients should be treated with postoperative adjuvant CAP to decrease distant failure and improve prognosis.

Survival of patients with advanced ovarian cancer treated with intermittent chemotherapy following cytoreductive surgery and adjuvant chemotherapy.

BACKGROUND: The purpose of this study was to report the duration of the progression-free interval (PFI) in advanced ovarian cancer patients who were treated with intermittent maintenance chemotherapy. METHODS: Between 1991 and 1998, 25 patients with stage III or IV ovarian cancer were enrolled in a trial of intermittent maintenance chemotherapy. All patients underwent cytoreduction surgery, and received adjuvant chemotherapy, after which they were treated with intermittent maintenance chemotherapy every 3 to 4 months for 2 years. RESULTS: The median PFI in the 25 women in the intermittent chemotherapy group was 25 months, while in the 32 patients in the control group it was 18 months (P = 0.0124). The median survival of women treated with the intermittent chemotherapy was 34 months, and for the control group patients, it was 35 months (P = 0.0672). Multivariate analysis in the intermittent chemotherapy group revealed that the only factor that correlated significantly with PFI was the status after adjuvant chemotherapy (P = 0.0137). In patients with no evidence of disease after the adjuvant chemotherapy, the median survival was 39 months in the intermittent chemotherapy group, and 35 months in the control group (P = 0.0156). The median PFI was 28 months in the intermittent chemotherapy group, and 18 months in the control group (P = 0.0012). CONCLUSION: It would be warranted to perform intermittent maintenance chemotherapy for patients with advanced ovarian cancer, if a clinically disease-free status could be achieved after completion of the standard treatment procedure.