Chemotherapy-induced thrombocytopenia and clinical bleeding in patients with gynecologic malignancy.

OBJECTIVES: Chemotherapy-induced thrombocytopenia seems to be a relevant problem and the risk or clinical bleeding in patients wim gynecologic malignancy is reported to be higher than other malignancy. In this study, the authors investigated chemotherapy-induced thrombocytopenia recently performed in all patients with gynecologic malignancy. MATERIALS AND METHODS: Between January 2009 and December 2011, the authors examined reported chemotherapy-induced thrombocytopenia using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. They analyzed the incidence and clinical features of chemotherapy-induced thrombocytopenia in patients with gynecologic malignancy. RESULTS: During this period they administered over 1,614 infusions (29 regimens) to 291 patients. Chemotherapy-induced thrombocytopenia occurred in 43 (14.8%) patients over 56 (3.5%) chemotherapy cycles. Bleeding occurred in 13 (4.5%) patients over 14 (0.9%) cycles. Platelet transfusions were administered for eight (2.7%) patients over eight (0.5%) cycles. Median platelet count at platelet transfusions was 17,000 /µl. Chemotherapy-induced thrombocytopenia was associated with more than five previous chemotherapy cycles, previous radiotherapy, disseminated disease, distant metastatic disease, poor performance status, and taxane-including regimens. Clinical bleeding was associated with previous radiotherapy, distant metastatic disease, poor performance status, and taxane-including regimens. CONCLUSIONS: Estimating bleeding risk factor such as previous radiotherapy, distant metastatic disease, poor performance status, and taxane-including regimens seem to be important for safe management of chemotherapy-induced thrombocytopenia.

Late recurrence of malignant melanoma mimicking primary peritoneal cancer.

BACKGROUND: Malignant melanoma is an extremely malignant tumor with an unpredictable metastatic profile with variable periods of remission. CASE: A 41-year-old woman presented with recurrent malignant melanoma which had clinical features of an acute state mimicking primary peritoneal cancer. The case was an unusual recurrence of malignant melanoma occurring seven years after diagnosis and treatment of malignant melanoma in the patient's arm. The diagnosis was established postoperatively by immunohistochemistry. CONCLUSION: A variety of imaging methods and pathological methods, including an exploratory laparotomy, may be necessary in cases of patients suspecting primary peritoneal cancer with a previous history of melanoma with possible metastatic dissemination. Urgent diagnosis and treatment of these patients seems to be critical.

Chemotherapy-related hypersensitivity reaction in Japanese patients with gynecologic malignancy.

PURPOSE OF INVESTIGATION: Chemotherapy-related hypersensitivity reaction seems to be problematic in the safe management of chemotherapy. In this study we investigated chemotherapy-related hypersensitivity reaction in patients with gynecologic malignancy. METHODS: Between January 2009 and December 2010, we examined hypersensitivity reaction (> or = grade2) using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence, clinical features, management, and outcome. RESULTS: We administered over 1,057 infusions (24 regimens) to 205 patients. We found a total of four hypersensitivity reactions (> or = grade 2) cases (carboplatin: 2; nedaplatin: 1; docetaxel: 1). Signs and symptoms were varied. In two cases, the same regimen was rechallenged by using anti-allergic drugs. The docetaxel case was successful. The carboplatin case was not successful. CONCLUSION: Chemotherapy-related hypersensitivity reaction (> or = grade2) does not occur frequently. In the case of platinum, especially, carboplatin, re-administering after hypersensitivity reaction should be done carefully though platinum is a key drug in patients with gynecologic malignancies.

Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with advanced ovarian cancer.

Paclitaxel and carboplatin combination chemotherapy (TC) is increasingly performed in ovarian cancer patients undergoing hemodialysis. However, appropriate dosage and time interval between the end of carboplatin administration and the initiation of hemodialysis remain unclear. We performed TC in a hemodialysis patient with ovarian cancer. Paclitaxel was administered at 150 mg/m2 for 3 h, followed by administration of 125 mg of carboplatin within 30 min to achieve a target area under the concentration/time curve (AUC) of 5.0 mg/ml x min by Calvert's formula. At 1 h after completing carboplatin administration, hemodialysis was performed for 4 h. Pharmacokinetic analysis showed we had achieved the desired serum concentration of paclitaxel. However, AUC of free platinum was very low (AUC = 0.98 mg/ml x min). Although the appropriate time interval between the end of carboplatin administration and the initiation of hemodialysis remains a controversial issue, our findings suggest that an interval of at least 1 h is required.

Phase II study of irinotecan plus doxorubicin for early recurrent or platinum-refractory ovarian cancer: interim analysis.

The aim of this study was to evaluate the efficacy and toxicity of irinotecan and doxorubicin in the treatment of patients with early recurrent or platinum-refractory ovarian cancer. Nineteen woman from five different institutions were treated. Two patients had platinum-refractory cancer, 11 had platinum-resistant disease, and 6 had platinum-sensitive tumors. An intravenous infusion of Irinotecan (50 mg/m(2)) was given on days 1, 8, and 15, while doxorubicin (40 mg/m(2)) was administered as an intravenous bolus on day 3. This treatment schedule was repeated every 4 weeks. Among the 13 patients defined as having platinum-refractory/platinum-resistant disease, 4 patients achieved a clinical response (30.8%, 95% CI: 9.1-61.4), while only one of 6 patients defined as having platinum-sensitive disease achieved a clinical response (16.7%, 95% CI: 0.4-64.1). Leukopenia and neutropenia were the major dose-limiting toxicities. Grade 3 or 4 leukopenia and neutropenia were noted in 24 (48%) and 33 (66%) of the courses, while febrile neutropenia occurred in 2 courses. Five patients (26%) had grade 2 or worse diarrhea during 7 courses. Our data demonstrated that this regimen might be comparable to standard approved agents in patients with early recurrent or platinum refractory ovarian cancer.

Clinical outcomes of uterine sarcomas: results from 14 years worth of experience in the Kinki district in Japan (1990-2003).

To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1-108) months and median disease-free period was 9 (0-96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival.

Long-term effects of hormone replacement therapy on bone mineral density in girls oophorectomized in adolescence.

The object of this study was to examine the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and physical development in oophorectomized adolescent girls. Two adolescent girls had bilateral ovaries removed as the treatment of advanced ovarian neoplasms at 12 years of age, and have been receiving HRT for more than 10 years. The changes in BMD and physical development were recorded. Both patients entered puberty and developed mature female physiques, despite the 3 years' absence of estrogen exposure immediately after oophorectomy. BMD recovered soon after the start of HRT and was kept within the normal range. Normal physical development, including bone mineral density, can be achieved with HRT in adolescent girls castrated before puberty.

Phase I study of combined radiation, hyperthermia and intra-arterial carboplatin for local recurrence of cervical cancer.

BACKGROUND: Patients with cervical cancer who develop pelvic recurrence after primary surgery are usually treated with radiation-based therapy. However, their prognoses are dismal. We conducted a phase I study of combined radiation, hyperthermia and intra-arterial (IA) carboplatin for local recurrence of cervical cancer. PATIENTS AND METHODS: Patients with local recurrence of cervical cancer without extrapelvic recurrence were included in this study. Carboplatin was given as a 5-min IA infusion without hydration just before pelvic radiation every day. External pelvic irradiation (1.8 Gy/day for 28 days) was performed according to local standard schedules. After 20 Gy had been administered, hyperthermia was performed once a week with a radio frequency heating system for four cycles. RESULTS: Fifteen patients were entered through the four dose levels of carboplatin. The maximum tolerated dose was determined to be 25 mg/m(2 )and the dose-limiting toxicities were leukocytopenia, neutrocytopenia and diarrhea. Grade 3/4 leukocytopenia and diarrhea were observed in nine (60%) and three (20%) of 15 patients. Tumor responses included five complete responses and nine partial responses, and the overall response rate was 93.3% (14 of 15) (95% confidence interval 59.4% to 100%). Tumor reductions were observed only at 20 Gy in 10 cases of 14 responders (71.4%). CONCLUSION: The combination therapy of radiation, hyperthermia and IA carboplatin is safe and well-tolerated for locally recurrent cervical cancer.

Uterine cervical adenofibroma associated with Turner's syndrome in a young woman.

A 32-year-old woman with Turner's syndrome complained of abnormal genital bleeding, which was diagnosed as a delivered myoma. Vaginal myomectomy was performed, and the tumor was histopathologically diagnosed as an adenofibroma of the uterine corpus. As these are extremely rare, we report this case with a review of some of the literature.

Acute disseminated intravascular coagulation developed during menstruation in an adenomyosis patient.

We report a case of acute disseminated intravascular coagulation (DIC) developed during menstruation in an adenomyosis patient. No known predisposing factor for DIC such as infection or pregnancy was involved in this case. As anticoagulation therapy and supplementation of coagulation factors quickly improve the state, surgical removal of the uterus was not required. We speculate that hemorrhage in the adenomyosis legion and subsequent local thrombosis played crucial role in pathophysiology of this case of acute DIC.

Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma.

Malignant transformation of a mature cystic teratoma of the ovary is rare, that of an adenocarcinoma is extremely rare. A 32-year-old woman was suspected as having a malignant transformation of her mature cystic teratoma of the ovary because the preoperative level of carcinoembryonic antigen (CEA) was extremely high. Resections of her ovarian cysts were performed, and this particular tumor was histopathologically diagnosed as an adenocarcinoma arising from a mature cystic teratoma of the left ovary. Because adenocarcinomas arising from mature cystic teratomas of the ovary are extremely rare, we report this case with a review of some of the literature.

The CA125 regression rate to predict overall survival differ between paclitaxel-containing regimen and nonpaclitaxel regimen in patients with advanced ovarian cancer.

In this study, we compare the time to normalization of CA125 after cytoreductive surgery between a paclitaxel-containing regimen and a non-paclitaxel regimen. This study demonstrates that CA125 regression in a paclitaxel-containing regimen was slower than that in a non-paclitaxel regimen. When we determine the CA125 regression rate to predict overall survival in ovarian cancer, we should take into account the kind of chemotherapy regimen, especially the use of paclitaxel.

A perforated sigmoid diverticulum abscess difficult to differentiate from an ovarian tumor.

We report a case of a perforated sigmoid diverticulum abscess that was difficult to differentiate from an ovarian tumor. A 53-year-old woman was diagnosed with an ovarian tumor, but laparotomy revealed a perforated sigmoid diverticulum abscess and appendicitis, with normal ovaries.

Phase I-II study of neoadjuvant chemoradiotherapy followed by radical surgery in locally advanced cervical cancer.

The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.

Expression of skeletal muscle cells apoptosis regulatory proteins in plasma-perfused VX2 carcinoma-bearing rabbits.

BACKGROUND: In tumor-bearing animals we found that the skeletal muscle apoptosis might be involved in muscle wasting. In this study, we investigated changes in the skeletal muscle cell apoptosis regulatory proteins after cyclic plasma-perfusion (CPP). MATERIALS AND METHODS: We studied changes in body weight, lean body mass (LBM), apoptotic index (AI) and expression of Bax and Bcl-2 in skeletal muscle in VX2 carcinoma-bearing rabbits. RESULTS: 20 days after tumor implantation, LBM had decreased by 5.06+/-1.10%, while the AI had increased to 40.5+/-3.20%. By 40 days, LBM had decreased by 11.0+/-0.81% and the AI was only 0.93+/-0.96%. Bax expression was detected in proportion to the AI, but no Bcl-2 expression was detected in either the experimental or control groups. CPP improved LBM, but did not prevent Bax expression. CONCLUSION: Skeletal muscle cell apoptosis related to Bax was concluded to be the cause of muscle wasting in VX2 carcinoma-bearing rabbits. CPP appears to reduce muscle wasting and increase LBM, but it did not suppress Bax expression or skeletal muscle cell apoptosis.

An antibody against anemia-inducing substance inhibits cation influx in red blood cells from cancer patients.

Resealed ghost of red blood cells (RBCs) from advanced cancer patients includes proteins with antigenicities common to an anemia-inducing substance that we separated from plasma of patients with advanced malignant neoplasms. Although cation influx in vitro in RBCs from a cancer patient is larger than that from a normal healthy volunteer, an antibody against anemia-inducing substance inhibited the in vitro cation influx in RBCs from the cancer patient. Activation of the cation influx with N-ethylmaleimide after reaction with the antibody reversed the effect to create a greater cation influx in RBCs from the patient, as compared with that from the healthy volunteer.

Angiogenesis in adipose tissues and skeletal muscles with rebound weight-gain after diet-restriction in rabbits.

The mechanisms of excessive body weight gain after diet-restriction are still unclear. In this study, we investigated expression of angiogenic factors in adipose tissue and skeletal muscle of rabbits which had rebound weight gains; trying to make inquiries into the mechanisms of this rebound weight gain. Ten rabbits were divided into two groups. One group had free food intake (group C), and the other group had restricted food intake until day 40 of the experiments and then had free food intake (group DR). Specimens of adipose tissue and skeletal muscle were collected from each rabbit on days 20, 40, and 60 after the initial examination, and expressions of CD34, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) were investigated. Expression of VEGF was significantly strong in the adipose tissue of group DR at the recovery period of body weight. In conclusion, rebound weight gain after a restricted-diet may be associated with angiogenesis in adipose tissue, and the angiogenesis may be induced by VEGF.

Expression of cyclooxygenase-2 in ovarian mature cystic teratomas with malignant transformation.

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor progression and angiogenesis and we previously reported that an increase in COX-2 expression might be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms. In this study, COX-2 expression of ovarian mature cystic teratomas with malignant transformation, a rare entity accounting for just 1.8% of all mature cystic teratomas, was investigated using immunohistochemical techniques. There were 89 cases of mature cystic teratomas treated with surgery as their initial therapy at Osaka City University Medical School Hospital between 1995 and 2001. Ten cases of these were selected for study; five cases of mature cystic teratoma with malignant transformation, and five cases of mature benign teratoma. Expressions of CD34, vascular endothelial growth factor (VEGF), and COX-2 were investigated. Expressions of VEGF and COX-2 were strong in tissues of mature cystic teratomas with squamous cell carcinoma; however, expressions of them were hardly apparent in mature benign teratomas and in mature cystic teratomas with adenocarcinomas. These results tend to suggest that COX-2 is associated with tumor growth and progression in mature cystic teratomas with squamous cell carcinoma, as opposed to mature benign teratomas and mature cystic teratomas with adenocarcinomas.

Involvement of angiogenesis in weight-loss in tumor-bearing and diet-restricted animals.

The body's weight loss mechanism while in a tumor-bearing state is still unclear. In this study, we investigated expressions of angiogenic factors in the adipose tissue of tumor-bearing and diet-restricted rabbits evaluating the differences between the two groups. We postulated that low nutrition induced vasculogenesis to transport nutrition in the adipose tissues of diet-restricted rabbits, unlike in tumor-bearing rabbits, and that vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were related to angiogenesis of the adipose tissues. Although we investigated the expressions of VEGF and PD-ECGF immunohistochemically in tumor-bearing and diet-restricted rabbits, there was no significant difference between the two groups. Whether angiogenesis of the adipose tissue in the diet-restricted animals may be observed during the nutritional recovery period should be investigated.