Intraperitoneal chemotherapy with taxanes for ovarian cancer with peritoneal dissemination.

Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.

Comparative study of systemic interferon alfa-2a plus isotretinoin versus isotretinoin in the treatment of recurrent condyloma acuminatum in men.

OBJECTIVES: Purpose of the present study was to evaluate the effectiveness of isotretinoin versus interferon alfa-2a plus isotretinoin in the treatment of recurrent condyloma acuminatum in 86 men. METHODS: Men were randomly assigned to group A (n = 42) who received isotretinoin 1 mg/kg orally daily until remission was achieved, but not more than 3 months, or to group B (n = 44) who received interferon alfa-2a 3 x 10(5) IU subcutaneously three times weekly until remission was achieved, but not more than 8 weeks, plus isotretinoin in the same dosage as in group A. RESULTS: The reduced duration of treatment to achieve remission was statistically significant in group B (2.18 versus 2.5 months; P < 0.01) and the recurrence rate was less in group B (4 of 44 versus 16 of 42; P < 0.01). CONCLUSIONS: The results of this study are encouraging and demonstrated that the combination of isotretinoin plus interferon alfa-2a achieves higher remission rates and a shorter duration of treatment than isotretinoin alone.

Skin-sparing mastectomy and immediate breast reconstruction: incidence of recurrence in patients with invasive breast cancer.

The aim of this study was to investigate whether skin-sparing mastectomy (SSM), which is gaining increasing importance and gives well-accepted cosmetic results, provides adequate treatment of the patients' oncologic disease. From 1995 to 2003, 60 patients diagnosed with invasive breast cancer were treated with SSM and complete axillary dissection. All patients underwent immediate breast reconstruction after primary surgery. Patients were treated either with a latissimus dorsi flap or with a transversus rectus abdominis myocutaneous flap. Depending on the intraoperative analysis of frozen sections, 14 patients were treated with preservation of the nipple-areola complex. During a median follow-up of 52 months (4-92 months), four local recurrences (6.6%) occurred. One patient was also found to have contralateral breast carcinoma. Three patients developed distant metastases, and two patients died of their disease a mean of 18 months after primary therapy. Factors associated with local recurrence were tumor size, poor tumor differentiation, and positive node involvement. SSM followed by immediate breast reconstruction is an alternative to modified radical mastectomy in a subset of patients with invasive breast cancer. The risk of local recurrence is low and is associated with such factors as tumor stage, poor tumor differentiation, and node-positive disease. This procedure does not increase the risk of distant metastases, which is comparable to that after other surgical approaches.

Peoscopic diagnosis of flat condyloma and penile intraepithelial neoplasia V scrotal reservoir.

The aim of the present study was to evaluate prospectively male sexual partners of women with flat condyloma (FC) or accuminata (CA) or cervical intraepithelial neoplasia (CIN) and to determine the incidence of scrotal involvement by HPV. Of the 218 patients, 20 (9.17%) revealed areas of acetowhite epithelium involving the anterior lateral and superior aspects of the scrotum. Eight patients (40%) also presented concomitant small telangiectatic lesions measuring 1-3 mm of the scrotum in the acetowhite areas, and one patient presented scrotal intraepithelial neoplasia grade I (SIN I). The new combination treatment schedule (cream 5-fluorouracil 5% + Interferon alpha-2 alpha) resulted in a 100% cure rate, with no recurrences for the follow-up period (11.52 months). Concluding, the scrotum appears to be an important and presently overlooked area in the evaluation of male patients, and interferon in combination with 5-FU cream seems to be a promising treatment for HPV infection.

Treatment of flat or accuminata condylomata of the female genital tract with interferon alpha-2 alpha.

This study was undertaken to assess the effectiveness of Interferon administered parenterally in the treatment of flat or accuminata condylomata of the female genital tract. One hundred and forty-three women with condylomata were treated with CO2 laser vaporization, 5-FU topical application and interferon alpha-2 alpha (IFN alpha-2 alpha) parenterally. The cure rates in the various treatment groups were analysed by the chi-square test. The cure rates of the treatments used in the patients with condylomata accuminata were similar (p>0.1). The best cure rate for flat condylomata was achieved with the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2 alpha (high dose) (p<0.01). In conclusion, Interferon can be used as adjuvant treatment in patients with recalcitrant condylomata accuminata and as first line treatment in combination with 5-FU and CO2 laser vaporization in patients with flat condylomata.

Cigarette smoking and vaginal atrophy in postmenopausal women.

The atrophy of the vaginal epithelium was studied clinically and cytologically on vaginal smears of 1638 healthy postmenopausal female non smokers and 531 healthy postmenopausal smokers (over 30 years), with a mean age of 58 years. A very strong statistically significant difference (p < 0.0001) in the atrophical vaginal changes between smokers and nonsmokers to the disadvantage of the smokers. Also a very statistically significant association (p < 0.0001) was observed between the cytological expression of the vaginal atrophy and duration at menopause of the non-smokers but no association in the cases of the smokers. Another important result of this study was that the smokers women had an early menopause (p < 0.0001), on average by 2 years sooner (mean age 48.5 years) than non-smokers (mean age 50.5 years). These results suggest that cigarette smoking has an effect on the vaginal squamous epithelium, increasing the atrophical changes and causing early menopause by mechanisms, some of which remain unclear.

Genital tuberculosis in a HIV infected woman: a case report.

The incidence of HIV-associated tuberculosis is increasing worldwide, especially in developing countries. HIV infected patients rapidly develop clinically significant disease, respond poorly to complete treatment and present with extrapulmonary tuberculosis. Although a relative increase of genital tuberculosis would be expected, this has not been reported. Probably, tuberculous systemic disease is diagnosed earlier, before genital tuberculosis occur. The present study is a report of case of a young African female patient, who was admitted with symptoms of acute pelvic inflammatory disease due to genital tuberculosis and proved to be HIV infected. The patient was managed by intravenous antibiotic administration, but since no clinical or laboratory improvement was achieved, a laparotomy and salpingooophorectomy was performed. Histopathology revealed tuberculosis and after that the patient proved to be HIV infected. Further investigation did not reveal pulmonary or other extragenital manifestation of tuberculosis. The only manifestation of HIV infection and genital tuberculosis was the symptoms of an acute pelvic inflammatory disease, which is extremely rare.

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.

INTRODUCTION: To minimize the surgical morbidity after lymphadenectomy, sentinel node biopsy (SLNB) has become fundamental in the management of different malignancies. We decided to evaluate sentinel lymph node (SNL) biopsies also in patients with endometrial cancer undergoing hysterectomy with lymphadenectomy. METHODS: In the setting of a prospective study we developed a technique for sentinel node biopsy of ten patients with histologically confirmed endometrial cancer. Prior to surgery 99m Tc Nanocol was injected in the peritumoral region by hysteroscopy. Six hours later lymphoscintigraphy was performed to identify the draining lymph nodes. During surgery we first detected the sentinel lymph node by a hand-held gamma tracer and then removed it. Surgery was completed by the standard therapy of total hysterectomy, bilateral salpingo-oophorectomy and pelvic and/or para-aortic lymphadenectomy. RESULTS: Scintigraphic identification was possible in eight out of ten patients. Intraoperative identification of sentinel lymph nodes was possible in seven out of eight patients. In five patients we found the sentinel lymph nodes in the pelvic region while the other two patients had bilateral sentinel nodes in the pelvic and para-aortic region. Histologically confirmed microscopic tumor metastases of the SLNs and para-aortic lymph nodes were only found in one case. The sentinel lymph nodes from the other six patients were free of tumor and accurately reflected the pathological status. CONCLUSION: The identification of sentinel lymph nodes in endometrial cancer is a practical and safe method. In order to improve this technique as a standard procedure for staging of endometrial cancer further studies with a larger number of patients have to be done.

Treatment of men with flat (FC) or acuminata (CA) condylomata with interferon alpha-2a.

This study was undertaken to assess the effect of CO2 laser vaporization, 5-fluorouracil 5% (5-FU) topical application and Interferon alpha-2a (IFA alpha-2a) in the treatment of C.A. or F.C. of the male genital tract. From March 1986 to September 1991, 1372 men, sexual partners of women with F.C. or C.A. or cervical intraepithelial neoplasia, were submitted to peoscopy. One thousand and nineteen (74.27%) men presented with various penile lesions caused by HPV (histologically confirmed); of these 505 were treated for C.A. or F.C. or a combination of F.C. and C.A. The best treatment modalities, irrespective of the kind of lesion, were found to be the combination of 5-FU plus IFN alpha-2a (high dose) (98.27%), the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2a (high dose) (93.93%) and the combination of CO2 laser vaporization plus 5-FU (87.23%). In conclusion we believe that IFN alpha-2a can be used with excellent results as first line treatment in combination with CO2 laser vaporization or/plus 5-FU in patients with C.A. or F.C. or combined condylomata.

Treatment of penile intraepithelial neoplasia (PIN) with interferon alpha-2a, CO2 laser (vaporization) and 5-fluorouracil 5% (5-FU).

This study was undertaken to assess the effectiveness of CO2 laser (vaporization), 5-FU topical application and Interferon (IFN alpha-2a) parenterally in the therapy of penile intraepithelial neoplasia (PIN). From March 1986 to September 1991, 1,372 men, sexual partners of women with condylomata accuminata or flat or cervical intraepithelial neoplasia (CIN), were submitted to peoscopy, of 1,019 men who presented with various lesions caused by human papillomavirus (HPV)-confirmed histologically-208 were treated for PIN. The best treatment modalities irrespective of grade of lesion were found to be the combination of 5-FU plus CO2 laser vaporisation plus IFN alpha-2a (high dose) (96.15%), the combination of 5-FU plus CO2 laser vaporization (87.09%) and the combination of CO2 laser vaporization plus IFN alpha-2a (high dose) (80%). It is concluded that IFN alpha-2a (low dose) can be used as first line treatment in combination with 5-FU in patients with PIN II and as an adjuvant treatment (high dose) in patients with recurrent PIN I and PIN III.

Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.

PURPOSE: Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity. METHODS: The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells. RESULTS: Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations. CONCLUSION: Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.

Comparative study of plasma carnitine: determination in the neonate and in normal delivery.

Free total plasma carnitine and acylcarnitine were determined in 20 mothers with normal deliveries and their neonates. Women of reproductive age and children constituted the comparative control groups. The mothers had lower total and free carnitine concentrations as compared to the neonates and the differences were statistically significant. The acylcarnitine values in the mothers were higher but the differences were not statistically significant. The women had higher total and free carnitine concentrations as compared to the children, while the values of acylcarnitine were higher in the children and the differences were statistically significant. The women had higher total free carnitine concentration as compared to the mothers and the differences were statistically very significant. In contrast the concentration of acylcarnitine was higher in the mothers than in the women and the difference was statistically significant. The children had higher total and free carnitine concentrations as compared to the neonates. On the other hand the concentration of acylcarnitine was higher in the neonates than in the children. The difference was statistically significant. It appears that transfer of maternal carnitine to the fetus constitutes the main factor of determining carnitine concentration in the neonate.

Congenital infection by human parvovirus B19 ascites-anaemia.

A case of intrauterine infection by human parvovirus B19 (HPV B19) manifested as ascites during pregnancy is presented. Ascites was diagnosed by ultrasound at 27 weeks' gestation. A caesarean section was performed at 37 weeks'. owing to affected mobility of the fetus. A pale, female infant with low haemoglobin and bradycardia was delivered. Polymerace Chain Reaction (PCR) lab tests revealed that the mother and the fetus were infected by HPV B19. The neonate was born with low haemoglobin (Hb = 10 g/dl) and with ascites; it was discharged in good general condition 50 days after delivery.

Effects of gestation age and of birth weight in the concentration of carnitine in the umbilical plasma.

To investigate the factors which affect the concentrations of the total, the free, and the acylcarnitine in neonates, blood was taken from the umbilical cord of 49 newborn infants ranging in gestation age (g. a.) from 32-40 weeks (mean g. a.: 36.8 +/- 2.6 weeks) and in birth weight (b. w.) from 1300 gr.-4300 gr. (mean b. w.: 2299 +/- 457 gr.). The carnitine and its fractions were studied in plasma. Twenty-eight of the neonates studied were premature (g. a. < or = 37 weeks) and 21 were full-term (g. a. > 37 weeks). The concentration of the total, free, and acylcarnitine in premature neonates was 28.0 +/- 2.3 mumol/L, 15.9 +/- 1.3 mumol/L, and 12.0 +/- 1.3 mumol/L, respectively. For the full-term neonates the respective concentrations were: 25.2 +/- 2.2 mumol/L, 14.6 +/- 1.5 mumol/L, and 10.7 +/- 1.5 mumol/L. These differences in concentrations between premature and full-term infants were statistically significant. For the total number of neonates studied the concentration of total, free, and of acylcarnitine was 26.8 +/- 2.6 mumol/L, 15.3 +/- 1.9 mumol/L, 11.5 +/- 1.5 mumol/L respectively. The calculation of the correlation coefficients for the total number of neonates showed the existence of a statistically significant negative correlation between the total, free and acetyl carnitine in terms of gestation age and birth weight. The comparative analysis of the correlation coefficients showed greater coefficient values between the total and the acylcarnitine in terms of birth weight. The latter finding, combined with the low rate of acylcarnitine decline, are indirect indications that the fetus uses carnitine as a source of energy, which affects the levels of total and acylcarnitine in the plasma.

Disposition of pesticides and toxicants in the human reproductive system in cases of acute poisoning.

The aim of this study was to estimate the penetration of some of the pesticides and toxicant substances in the human reproductive system. This knowledge is valuable because of the possible adverse influence of these substances on the human reproduction system and the development of the foetus during pregnancy. The existing data is mainly concerned with the results of experimental studies on animals or epidemiological studies. Here we report data concerning the disposition of several toxic xenobiotics (pesticides and solvents) in the tissues of the human reproductive system as well as in other organs and glands. Data was collected from cases of acute poisonings and derived mostly from autopsy materials. Xenobiotics were found to penetrate sampled tissues such as the testes, ovaries, epididymis, uterus, thyroid gland, as well as other human tissues. Further studies will clarify and confirm peculiarities of the penetration of a wide range of substances in various body tissues and will be the base of the estimation of the role of these toxicants in human reproductive ability and the outcome of pregnancy in humans.

Fatal and non-fatal outcome by accidental intoxication with paint thinner.

Although poisonings (fatal and non-fatal) due to intentional or accidental acute exposure to toluene or toluene mixture fumes have been previously reported in the literature, several issues concerning lethal doses or lasting post-exposure neuropathological impairments still remain unclear. Two male painters (18 and 30 years old) were accidentally exposed to toxic concentrations of paint diluent fumes containing toluene (TL), acetone (ACT) and methyl ethyl ketone (MEK) (60:15:15 w/w/w respectively) during their work in an underground reservoir. Both workers were found unresponsive by colleagues and were immediately transferred to the regional hospital. On admission, the younger man was pronounced dead, while the other remained in the intensive care unit for 3 days and then 4 days in the internal medicine ward. TL, ACT and MEK concentrations in blood samples taken from the survivor on admission were 6.3, 30.6 and 40.5 microg/mL. Postmortem toxicology of the dead worker revealed TL, ACT and MEK blood levels of 12.4, 90.8 and 80.4 microg/mL respectively. The solvent levels in the liver, kidney, lung, brain, testis and gland were also quantified and showed a somewhat similar distribution of the chemicals among these tissues with the highest levels found in the brain and the liver. The fatal and the non-fatal outcome that resulted despite similar intoxication conditions, most probably demonstrates the interindividual tolerance among the painters who also had similar body weights. The surviving painter did not develop any neuropsychological impairment in post-exposure time. The reported case strongly emphasizes the necessity to take precautions when using paint diluents in enclosed spaces.

Small cell ovarian cancer in adolescents: report of two cases and review of the literature.

Ovarian small cell carcinoma is a rare and highly malignant neoplasm carrying a poor prognosis. Although combination chemotherapy remains the cornerstone of treatment due to the rarity of these tumors, no regimen can be recommended as standard of care although in the majority of cases platinum-based regimens are used. Herein, we report two cases of small cell carcinoma of the ovaries along with a review of the relevant literature.

Endometriosis and infertility: a multi-cytokine imbalance versus ovulation, fertilization and early embryo development.

Endometriosis is tightly linked to infertility which is manifested at very early or more advanced stages of the gestational cycle. Alteration on the production of a great number of cytokines/growth factors can be accused for problems on ovum maturation, fertilization or implantation. Yet, macroscopically these stages are characterized by the inability of conception. A closer look of the cytokinic profile during the conceptional and early gestational cycle could, however, localize the problem and allow a therapeutic approach. In this commentary, going through the cytokine requirement during ovulation, fertilization and the early stages of pregnancy, it became possible to specifically define the harmful endometriosis-induced cytokines for each of the conceptional and early gestational stages. Thus, regulating the levels of interferon-gamma and tumor necrosis-alpha will facilitate ovulation and fertilization, whereas adjusting the levels of interleukin-1beta and colony stimulating gactor-1 will facilitate implantation.