Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients.

BACKGROUND: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed. RESULTS: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10). CONCLUSIONS: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

Randomized open label phase III trial of CEOP/IMVP-Dexa alternating chemotherapy and filgrastim versus CEOP/IMVP-Dexa alternating chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). A multicenter trial by the Austrian Working Group for Medical Tumor Therapy.

Primary end point of this trial was to reduce neutropenic infections during the treatment of aggressive NHL with CEOP/IMVP-Dexa (cyclophosphamide, epirubicin, vincristine, prednisolone ifosfamide, methotrexate, VP-16, and dexamethasone). Further, we studied the influence of filgrastim on dose intensity of CEOP/IMVP-Dexa, on the rate of complete remissions, on the time to relapse, and on survival. Eighty-five patients with untreated large-cell NHL were randomized to one of two treatment arms; 74 patients were eligible. Thirty-eight patients in arm 1 were treated with CEOP/IMVP-Dexa chemotherapy and filgrastim, 36 in arm 2 with CEOP/IMVP-Dexa chemotherapy alone. In arm 1 filgrastim was self-injected by the patients at 5 micrograms/kg body wt. s.c. daily, except on the days when cytotoxic drugs were given. During treatment we did weekly complete blood counts. Median leukocyte counts were 10.91 x 10(9)/l and 5.46 x 10(9)/l in arm 1 and 2, respectively (p = 10(-6)). Median neutrophil counts were 7.7 x 10(9)/l in arm 1 and 2.72 x 10(9)/l in arm 2 (p < 10(-6)). Median neutrophil nadirs were 0.199 x 10(9)/l and 0.213 x 10(9)/l in arm 1 and 2, respectively (p = 0.09). Mean platelet nadirs were 95 and 152 x 10(9)/l (p = 0.000004) and mean hemoglobin nadirs 83.95 g/l and 92.78 g/l (p = 0.00558) in arm 1 and 2, respectively. Dose intensity of CEOP/IMVP-Dexa was 82.3% and 76.2% in arm 1 and 2, respectively (p = 0.041). Forty-two percent and 58% of patients experienced a febrile neutropenia in arm 1 and 2, respectively (not significant, NS). Median time to first neutropenic infection was in treatment week 11 and 6 in arm 1 and 2, respectively (NS). There was no significant difference in rate, duration, and kind of infection, duration of hospitalization, or antibiotic treatment. Seven toxic deaths occurred, all due to neutropenic infection, 6 and 1 in arm 1 and 2, respectively (p = 0.0732). Four of the six patients, who died of infection in arm 1 were older than 60 years. Complete remission rate was 83% and 66.7% in arm 1 and 2, respectively (NS). After a median observation time of 3 years there was no difference in time to relapse or survival. Filgrastim increases leukocyte and neutrophil counts and dose intensity, if used with CEOP/IMVP-Dexa chemotherapy in high-grade lymphomas. There was no significant effect on febrile neutropenia or infections. The more frequent fatal neutropenic infection rate in the filgrastim arm was not statistically significant. It is most appropriate to explain it by the patient's age in combination with the high dose intensity. The small increase in dose intensity had no effect on survival but probably decreased hemoglobin levels and platelet counts in arm 1. We were unable to show a benefit for filgrastim in combination with CEOP/IMVP-Dexa.

Evaluation of adnexal masses using three-dimensional ultrasonographic technology: preliminary report.

The purpose of the current study was to demonstrate the ability of three-dimensional ultrasonographic technology to enhance the morphologic scoring system and further improve the ability to differentiate benign from malignant ovarian masses. We performed conventional two-dimensional and three-dimensional transabdominal and transvaginal ultrasonography on eight women with adnexal masses. All patients underwent exploratory laparotomy or diagnostic laparoscopy. The three-dimensional ultrasonographic findings were compared with the two-dimensional ultrasonograms, the intraoperative observations, and gross and histopathologic findings. The morphologic scoring system as described by Sassone and coworkers was adopted, with scores of less than 9 suggestive of benign lesions, and this system was applied in both the two-dimensional and three-dimensional ultrasonographic examinations. The morphologic scores were subsequently compared. The images were dissected in the XYZ planes, and the areas suggestive of malignancy, as suggested by two-dimensional ultrasonography, were determined to be either negative or positive and confirmatory. In each of the eight adnexal masses, three-dimensional ultrasonography confirmed the preoperative diagnoses. The morphologic scores did not differ between two-dimensional and three-dimensional ultrasonograms for the benign cysts. In one case of benign solid fibroma, both the two-dimensional and three-dimensional gray scale morphologic scores were falsely positive at greater than 9. In one case of malignant serous papillary cystadenocarcinoma the two-dimensional morphologic score was a 9, where- as the three-dimensional score was 13. This difference in scores can be attributed to the additional views available with three-dimensional volume scanning, which allowed better characterization of the pathologic conditions. In addition, three-dimensional sonographic technology had the added advantage of high-speed image acquisition and recording to decrease the time of scanning to improve patient comfort. Furthermore, three-dimensional ultrasonography allowed the real-time analysis of the acquired image data to be conducted at a later time when the patient is off the examination table. Our preliminary results suggest that three-dimensional transvaginal ultrasonographic technology can enhance and facilitate the morphologic evaluation of both benign and malignant adnexal masses.

Effects of coping style on psychological reactions of low-income, minority women to colposcopy.

Patterns of coping and adjustment in 36 low-income, minority women with positive cytologic smears were assessed prior to diagnostic follow-up examination (colposcopy). Subjects were divided into high monitors (who attend to threatening cues) and low monitors (who avoid threatening cues) on the basis of their scores on the Miller Behavioral Style Scale, a well-validated measure of coping style. Multivariate analysis of variance showed that high monitors worried more about the seriousness of their condition, expressed more concern about the immediate sensory and procedural aspects of the diagnostic examination and felt more responsible for the onset and course of their disease as compared to low monitors. However, they were no more likely to be concerned about the overall importance or long-term consequences of their abnormal smears. Finally, high monitors displayed greater symptoms of intrusive and avoidant ideation in relation to their medical status. These results were independent of sociodemographic and medical confounding variables. Consistent with results in other populations, the findings suggest that it may be useful to assess attentional coping dispositions in minority populations with high-risk gynecologic conditions and to target psychosocial interventions accordingly.

[Disordered peripapillary microcirculation in glaucoma patients]. / Störung der peripapillären Mikrozirkulation bei Glaukomatienten.

To study the haemodynamics of the peripapillary choroid, perfusion pressure videoangiography (PVA) was performed in six healthy subjects and in seven patients with primary open-angle glaucoma (poag). In healthy subjects the peripapillary part of the choroid starts filling at distinctly lower ocular perfusion pressures than other parts of the choroid. The mean difference in perfusion pressure between peripapillary and perimacular filling was 13.6 mmHg in the six healthy subjects. A different filling pattern of the choroid was found in the seven glaucoma patients. The mean difference in perfusion pressure between the beginning of peripapillary and the beginning of perimacular perfusion of the choroid was found to be as small as 1.9 mmHg. That the filling of the peripapillary choroid observed by PVA in healthy subjects is found to start at lower perfusion pressures than in the other parts is explained by autoregulative dilatation of the peripapillary choroidal arterioles resulting from artificially raised intraocular pressure during the PVA examination. In the poag patients the peripapillary choroidal arterioles were dilated either insufficiently or not at all. The following conclusions are drawn: (1) The peripapillary choroid of healthy persons shows effective autoregulation securing the blood supply to the prelaminar part of the optic nerve. (2) In poag the peripapillary choroid has lost the capability of effective autoregulation.

Fluorescein angiography in the follow-up study of choroidal melanoma after 106Ru/106Rh plaque therapy.

Characteristic angiographic findings of 220 patients before and after 106Ru/106Rh plaque irradiation of choroidal melanomas are described. Fluorescein angiography may provide valuable information, especially of the different stages of tumor regression after local brachytherapy.

Different deoxyribonucleases in human lymphocytes.

The distribution pattern of deoxyribonuclease activities in human lymphocytes has been examined by micro-disc-electrophoresis. Four groups of deoxyribonuclease activities, differing in their electrophoretic mobility, in the nature of their optimal substrate and in their optimal incubation conditions, are characterized. There are two alkaline DNase-activities. One corresponds to DNase I (EC 3.1.4.5), the other having pH optimum of about pH 9.0, prefers denatured DNA as substrate and is not dependent on divalent cations. The fractions with an acid pH optimum can be subdivided into two groups, which differ in their activity towards native DNA, towards denatured DNA, in their activity when succinate is present and in their pH optimum.