Differential expression of thioredoxin binding protein-2/Txnip in human placenta: Possible involvement of hypoxia in its suppression during early pregnancy.

AIM: Thioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2-/- ). METHODS: Protein and mRNA expression of TBP-2 in human placenta from each trimester were analyzed by immunohistochemistry, Western blots, and by quantitative reverse-transcriptase-polymerase chain reaction. The effect of hypoxia on TBP-2 expression was tested using an explant culture of human placenta. In TBP-2-/- mouse placenta, we detected PPAR mRNA expression. RESULTS: TBP-2 was located in syncytiotrophoblasts and cytotrophoblasts, and also in the endothelium in human placenta. Its expression in the placenta was low in the first trimester, and increased in the second and third trimesters. Hypoxia decreased TBP-2 mRNA and protein expression in human placental explant culture. In TBP-2-/- mice, placental mRNA levels of PPARα and γ were significantly suppressed compared with those in wild-type mice. CONCLUSION: Hypoxia suppresses TBP-2 gene expression, which may ultimately alter placental development.

Role of premature leptin surge in obesity resulting from intrauterine undernutrition.

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

Thioredoxin binding protein-2 inhibits excessive fetal hypoglycemia during maternal starvation by suppressing insulin secretion in mice.

Glucose is a major fuel for fetal development. Fetal blood glucose level is mainly dependent on maternal blood glucose concentration, though it is also regulated by fetal insulin level. Thioredoxin binding protein-2 (TBP-2), which is identical to vitamin D3 up-regulated protein (VDUP1) and thioredoxin interacting protein (Txnip), was recently reported to be a key transcriptional factor controlling glucose metabolism. Here, we elucidated the functions of TBP-2 in maintaining blood glucose homeostasis during the fetal period. TBP-2(+/-) female mice were mated with TBP-2(+/-) male mice; beginning 16.5-d post coitum, pregnant mice were fed or fasted for 24 h. Under conditions of maternal starvation, the blood glucose levels of TBP-2(-/-) fetuses were significantly lower than those of TBP-2(+/+) fetuses, corresponding to the elevated plasma insulin levels of TBP-2(-/-) fetuses compared with those of TBP-2(+/+) fetuses. There was no difference between TBP-2(+/+) and TBP-2(-/-) fetuses in terms of their pancreatic beta-cell masses or the expression of placental glucose transporters under conditions of either maternal feeding or fasting. Thus, during maternal fasting, fetal TBP-2 suppresses excessive insulin secretion to maintain the fetus's glucose levels, implying that TBP-2 is a critical molecule in mediating fetal glucose homeostasis depending on nutrient availability.

Isocaloric high-protein diet ameliorates systolic blood pressure increase and cardiac remodeling caused by maternal caloric restriction in adult mouse offspring.

Epidemiologic studies have shown that in utero malnutrition is a risk factor for adult cardiovascular disease (CVD). Recently, we reported a mouse animal model of 30% maternal caloric reduction, in which offspring showed a significant increase in systolic blood pressure (SBP) as well as in cardiac remodeling-associated morphological parameters such as cardiac enlargement and coronary perivascular fibrosis in adulthood. Using a similar animal model, we here demonstrated that an increased level of protein consumption during an undernourished pregnancy (high-protein diet; HPD) corrected for the development of CVD risk factors found in fetal undernourishment with less protein consumption (standard-protein diet; SPD). In contrast, maternal ad libitum feeding with HPD resulted in significantly elevated SBP and cardiac enlargement in offspring at 16 wks. Appropriate maternal protein ingestion might partly protect against the development of CVD risk factors in offspring.

Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring: possible involvement of local cardiac angiotensin system in developmental origins of cardiovascular disease.

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.

The relationship between maternal plasma leptin levels and fetal growth restriction.

Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and Delta SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and Delta SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.

[Obesity in offspring with maternal undernutrition during pregnancy].

Recent epidemiology demonstrates higher rate of obesity and metabolic syndrome in offspring with undernutrition in utero. IUGR babies with intrauterine undernutrition grow rapidly to catch up with normal growth course. Leptin is an adipocyte derived satiety factor that regulates food intake and energy expenditure. We demonstrated in mice model with maternal food restriction during pregnancy that premature leptin surge during neonatal catch up growth of the offspring lead them to impaired leptin sensitivity and obesity in adulthood.

Spontaneous regression of congenital cystic adenomatoid malformation of the lung: longitudinal examinations by magnetic resonance imaging.

We report a case of large cystic adenomatoid malformation of the lung (CCAM), which occupied almost the entire left lung with a prominent mediastinal shift at 24 weeks of gestation. The volume of the lesion, determined by magnetic resonance imaging (MRI), was 27.0 cm3. Subsequent MRI and ultrasound examinations revealed a spontaneous resolution of the lesion at 32 and 36 weeks of gestation without a mediastinal shift, when the lesion volume was 12.8 cm3 and 5.6 cm3, respectively. At 37 weeks of gestation, a mature male baby weighing 2638 g with an Apgar score of 7 was delivered by elective cesarean section. A lobectomy of the left upper lobe of the lung was carried out at 3 days of age, due to an enlargement of the CCAM after birth.

Resistin is expressed in the human placenta.

The mechanism for decreased insulin sensitivity in pregnant women is not fully clarified. Resistin, a novel peptide hormone, is specifically expressed in the adipose tissue and decreases insulin sensitivity in rodents. In the present study, we demonstrate resistin gene expression in the human placental tissue, mainly in trophoblastic cells. The resistin gene expression in term placental tissue was more prominent than was seen in the first trimester chorionic tissue. In contrast resistin gene expression in adipose tissue was rather weak and remained unchanged by pregnancy. Thus, resistin is a newly isolated placental hormone in humans which may modulate insulin sensitivity during pregnancy.

Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.

Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor. To elucidate the involvement of labor in the increase in PGI(2) production during labor, we next examined the effect of labor-like cyclic mechanical stretch on PGI(2) production by cultured human myometrial cells. Pregnancy specifically increased COX-1 and PGIS protein expression in the myometrial tissues before labor (P < 0.01 for both). Cyclic mechanical stretch augmented PGIS promoter activity, via activation of activator protein-1 site, and PGIS mRNA and protein expression in cultured human myometrial cells and resulted in a 3.5-fold increase in the concentration of 6-keto-prostaglandin F(1alpha), the stable metabolite of PGI(2), in the culture medium (P < 0.05). However, stretch did not affect the levels of prostaglandin E(2), prostaglandin F(2alpha), or thromboxane A(2) secreted into the same culture media. These results suggest that cyclic mechanical stretch during labor may contribute to the increase in the PGI(2) concentration in the maternal plasma during parturition.

Site-specific augmentation of amnion cyclooxygenase-2 and decidua vera phospholipase-A2 expression in labor: possible contribution of mechanical stretch and interleukin-1 to amnion prostaglandin synthesis.

OBJECTIVE: To investigate a possible site-specific augmentation of prostaglandin (PG) synthesis in the fetal membranes during labor. METHODS: We used reverse transcriptase-polymerase chain reaction or Western blot analysis to evaluate the expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-1, -2 (COX-1, -2), in both the upper and lower parts of the amnion, chorion laeve, and decidua vera tissues from term pregnant women before (n = 8) and after labor (n = 24). Prostaglandin E2 (PGE2) secretion from amnion-derived WISH cells was assessed using enzyme-linked immunosorbent assay after stimulation by cyclic mechanical stretching and interleukin-1 (IL-1). RESULTS: The expression of cPLA2 and COX-1 and COX-2 mRNAs was detected in all samples examined. Western blot analysis revealed that COX-2 expression in the upper part of the amnion, chorion laeve, and decidua vera tissues after labor was 4.7-, 4.9-, and 3.7-fold higher than that before labor, respectively (P < .05 for all). The cPLA2 protein expression in the upper part of the amnion and chorion laeve tissues after labor was 14.0- and 8.8-fold higher than that before labor, respectively (P < .05 for both). Moreover, in specimens obtained after labor, the amnion COX-2 expression and the decidua vera cPLA2 expression in the lower part of the fetal membrane was 1.9- and 2.6-fold higher than the respective levels in the upper part (P < .05 for both). In an in vitro study, cyclic mechanical stretching significantly enhanced IL-1-augmented PGE2 secretion from WISH cells. CONCLUSION: In the lower part of the amnion and decidua vera tissues, adjacent to the dilating cervical canal, PG synthesis was upregulated site specifically after labor. Such enhancement of amnion PG synthesis might be regulated at least partly by IL-1 and cyclic distension.

17beta-estradiol up-regulates prostacyclin production in cultured human uterine myometrial cells via augmentation of both cyclooxygenase-1 and prostacyclin synthase expression.

OBJECTIVE: To investigate whether 17beta-estradiol elevates prostacyclin (PGI(2)) production in human myometrial cells in the middle of gestation. METHODS: The concentration of 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in the culture medium was assessed using enzyme-linked immunosorbent assay (ELISA). Western blot analysis and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using TaqMan (Applied Biosystems, Foster City, CA) technology were performed to evaluate the expression of cytosolic phopholipase A(2) (cPLA(2)), cyclooxygenase-1 (COX-1), COX-2, and prostacyclin synthase (PGIS) in cultured human myometrial cells prepared from second trimester pregnant women (n = 3) after stimulation with 17beta-estradiol. RESULTS: Treatment with 17beta-estradiol (4-400 nM) dose-dependently elevated PGI(2) secretion from cultured human myometrial cells. Western blot analysis detected cPLA(2) and COX-1 and PGIS protein expression in the cultured human myometrial cells; however, COX-2 protein expression was below the detection sensitivity. Stimulation with 40-nM 17beta-estradiol significantly up-regulated protein and mRNA expression of both COX-1 and PGIS. CONCLUSION: 17beta-Estradiol from placenta may contribute to the augmentation of PGI(2) production in the human myometrium in the middle of gestation via up-regulation of both COX-1 and PGIS expression.

Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer.

OBJECTIVE: The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated. METHODS: Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient. RESULTS: In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient's follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses. CONCLUSIONS: These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient.

Angiotensin II receptor blocker candesartan cilexetil, but not hydralazine hydrochloride, protects against mouse cardiac enlargement resulting from undernutrition in utero.

Epidemiologic studies have shown that malnutrition in utero is a risk factor for cardiovascular disease (CVD) in adulthood. Recently, we reported a mouse animal model of 30% maternal caloric reduction, in which adult offspring (undernourished [UN] offspring) showed a significant increase in cardiac remodeling-associated parameters, such as cardiac enlargement (CE) and coronary perivascular fibrosis (CPVF), as risk factors for CVD. To investigate the possible involvement of the angiotensin system, an angiotensin II receptor antagonist, candesartan cilexetil, or a nonspecific vasodilator, hydralazine hydrochloride, was administrated via a subcutaneously implanted miniosmotic pump to the UN offspring from 9 to 17 weeks after birth. Administration of candesartan cilexetil, but not hydralazine hydrochloride, significantly protected against CE. While administration of not only candesartan cilexetil but also hydralazine hydrochloride prevented an augmentation of CPVF. The angiotensin system seems to make a critical contribution to the developmental origins of cardiac enlargement.

Isocaloric high-protein diet as well as branched-chain amino acids supplemented diet partially alleviates adverse consequences of maternal undernutrition on fetal growth.

Maternal undernutrition causes fetal growth restriction. Protein is a vital dietary nutrient for fetal growth, and branched-chain amino acids (BCAA) are noted to have anabolic actions. In this study, we investigated the effects of maternal high-protein diet or BCAA-supplemented diet upon fetal growth under the condition of maternal calorie restriction. Pregnant mice were calorie-restricted (undernutrition: UN), using either a standard diet (S-UN group), high-protein diet (HP-UN group), or BCAA-supplemented diet (BCAA-UN group) to 70% of the control; dams fed ad libitum with a standard diet (S-NN group) from 10.5days post coitum (dpc) to 18.5dpc. The fetal weights of UN groups were significantly decreased compared to that of S-NN. However, the fetal weights of HP-UN and BCAA-UN were significantly higher by 5% and 4%, respectively, than those of S-UN, concomitant with augmentation of the gene and protein expressions of IGF-I and IGF-II in fetal liver. A high-protein diet as well as BCAA-supplemented diet partially improved fetal growth restriction caused by maternal calorie-restriction, suggesting a pivotal role of them in the amelioration of fetal growth restriction.

Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient Ob/Ob mice.

OBJECTIVE: Epidemiological evidence has revealed that undernutrition in utero is closely associated with obesity and related detrimental metabolic sequelae in adulthood. Recently, using a wild-type (wt) mouse model in which offspring were exposed to intrauterine undernutrition (UN offspring), we reported that the premature leptin surge during neonatal growth promotes lifelong changes in energy regulating circuitry in the hypothalamus, thus playing an important role in the development of pronounced obesity on a high-fat diet (HFD) in adulthood. Here, we further evaluate the essential involvement of leptin in the developmental origins of obesity using leptin-deficient ob/ob mice. METHODS AND PROCEDURES: We assessed the progression of obesity on an HFD in adult leptin-deficient ob/ob male mice that were exposed to intrauterine undernutrition by maternal food restriction (ob/ob UN offspring) or to leptin treatment during the neonatal period; this treatment is comparable to the premature leptin surge observed in the wt-UN offspring. RESULTS: On an HFD, the body weight of the male ob/ob UN offspring paralleled that of the ob/ob offspring exposed to normal intrauterine nutrition (ob/ob NN offspring). In contrast, early exposure to leptin in the ob/ob NN offspring during early neonatal growth reproduced the development of pronounced obesity on an HFD in adulthood. DISCUSSION: The presence of leptin and associated energy regulation are indispensable in the acceleration of obesity on an HFD caused by undernutrition in utero. The premature leptin surge plays an essential role in the developmental origins of obesity as a programming signal during the early neonatal period.

Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy.

OBJECTIVES: To clarify the anatomy necessary for the nerve sparing Okabayashi's radical hysterectomy, we meticulously separated the blood vessels and connective tissues to preserve the pelvic splanchnic nerve, the hypogastric nerve, and the bladder branch of the inferior hypogastric plexus under magnification (x2.5) during the Okabayashi radical hysterectomy. METHODS: Twenty-four patients (FIGO stage IB, n=22, and stage IIA, n=2) underwent meticulous nerve sparing radical hysterectomy during 2004 to 2006. Postoperative assessment of bladder function consisted of the time to (a) achieve a postvoid residual urine volume (PVR) less than 50 ml, (b) obtain a sensation of bladder fullness, and (c) obtain satisfaction of micturition. RESULTS: Isolation of the deep uterine vein could preserve one of the branches of the pelvic splanchnic nerve. The hypogastric nerve in the lateral rectal wall was isolated to the inferior hypogastric plexus. During the division of the posterior leaf of the vesicouterine ligament (VUL), isolation of the inferior vesical vein could reveal the bladder branch from the inferior hypogastric plexus. Only the uterine branch from the inferior hypogastric plexus was isolated and divided. Then, the T-shaped nerve plane consisting of the hypogastric nerve, the pelvic splanchnic nerve and the bladder branch from the inferior hypogastric plexus is preserved. Urinary functions: (a) 11 out of 24 patients had measured PVR of less than 50 ml by postoperative day (POD) 14 and all patients had achieved this by day 21 (mean POD: 14.64+/-2.04). (b) Twenty-two out of 24 patients reported a sensation of bladder fullness by POD 14 and all by POD 21 (mean POD: 11.25+/-1.78). (c) Seventeen out of 24 patients reported satisfaction of micturition by POD 14 and all by POD 21 (mean POD: 12.34+/-2.32). CONCLUSION: In order to accomplish the nerve sparing Okabayashi's radical hysterectomy, it is necessary to meticulously divide the posterior leaf of the vesicouterine ligament. By the separation of the inferior vesical vein in the posterior leaf of the vesicouterine ligament, the bladder branch from the inferior hypogastric plexus can be identified and preserved. All patients recovered their urinary function completely by POD 21.

Precise anatomy of the vesico-uterine ligament for radical hysterectomy.

OBJECTIVES: To clarify the anatomy of the vesico-uterine ligament (VUL), we meticulously separated the VUL under magnification (x2.5) during Okabayashi's radical hysterectomy. METHODS: Fifty-nine patients (TNM nomenclature: pTIb: 39, pT2a: 5, pT2b: 7, after trans-arterial anticancer-drug infusion treatment for the cervical cancer: 8) underwent this meticulous operation. Blood loss was recorded at two separate time points: during the separation of the VUL and after removal of the uterus. RESULTS: After complete separation of the uterine artery and superficial uterine vein from the ureter, we could identify the genuine connective tissue of the anterior leaf of the VUL in which we isolate and divide a distinct bundle of blood vessels: the cervicovesical vessels that cross over the ureter from the bladder to the cervix. The remaining tissues in the anterior leaf is only avascular connective tissue. The posterior leaf of the VUL is the tissue residing under the ureter connecting the posterior wall of the bladder and the lateral cervix/upper lateral vagina. In the connective tissues, we identified the middle and inferior vesical veins connecting with the deep uterine vein. The division of these veins could separate the urinary bladder with ureters completely from the lateral cervix and upper vagina. The mean blood loss during the separation of the VUL was 20+/-10 g (N=59) and after radical hysterectomy was 189+/-91.6 g (N=59). CONCLUSION: A precise network of blood vessels in the VUL is identified. The knowledge of this anatomy is important to perform radical hysterectomy.

Role of salvage cytoreductive surgery in the treatment of patients with recurrent ovarian cancer after platinum-based chemotherapy.

OBJECTIVES: The role of cytoreductive surgery, which is well established in the primary treatment for epithelial ovarian cancer, is controversial in recurrent disease. The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with recurrent ovarian cancer after platinum-based chemotherapy. METHODS: We conducted a retrospective analysis of 46 patients with recurrent epithelial ovarian cancer treated at our department between 1988 and 2003. Twenty-three patients underwent salvage cytoreductive surgery (cytoreductive group), and the other 23 patients were treated without surgery (control group). RESULTS: Patients in cytoreductive group had a median survival of 41.7 months after recurrence, which was significantly longer than control group (18.8 months; P < 0.01). The duration of stay at home and the period oral intake was preserved were significantly longer in the cytoreductive group. In the cytoreductive group, survival was influenced by the residual disease after surgery (residual tumor diameter, <2 cm vs >2 cm; median survival, 50 months vs 35.2 months; P < 0.05). However, the number of recurrent sites (solitary vs multiple) and the lengths of treatment-free intervals after primary treatment (<6 months vs >6 months) showed no significant influence on survival. CONCLUSIONS: The application of cytoreductive surgery might improve the prognosis of patients with recurrent ovarian cancer if the tumor was resectable. Preserved prognoses of platinum-resistant disease with short treatment-free interval demonstrated in this study suggest that the concept of maximum cytoreduction might be introduced in the treatment of recurrent disease in the future.