Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.

Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance.

BACKGROUND: PSI-BLAST, an extremely popular tool for sequence similarity search, features the utilization of Position-Specific Scoring Matrix (PSSM) constructed from a multiple sequence alignment (MSA). PSSM allows the detection of more distant homologs than a general amino acid substitution matrix does. An accurate estimation of the weights for sequences in an MSA is crucially important for PSSM construction. PSI-BLAST divides a given MSA into multiple blocks, for which sequence weights are calculated. When the block width becomes very narrow, the sequence weight calculation can be odd. RESULTS: We demonstrate that PSI-BLAST indeed generates a significant fraction of blocks having width less than 5, thereby degrading the PSI-BLAST performance. We revised the code of PSI-BLAST to prevent the blocks from being narrower than a given minimum block width (MBW). We designate the modified application of PSI-BLAST as PSI-BLASTexB. When MBW is 25, PSI-BLASTexB notably outperforms PSI-BLAST consistently for three independent benchmark sets. The performance boost is even more drastic when an MSA, instead of a sequence, is used as a query. CONCLUSIONS: Our results demonstrate that the generation of narrow-width blocks during the sequence weight calculation is a critically important factor that restricts the PSI-BLAST search performance. By preventing narrow blocks, PSI-BLASTexB upgrades the PSI-BLAST performance remarkably. Binaries and source codes of PSI-BLASTexB (MBW = 25) are available at https://github.com/kyungtaekLIM/PSI-BLASTexB .

Protein sequence-similarity search acceleration using a heuristic algorithm with a sensitive matrix.

Protein database search for public databases is a fundamental step in the target selection of proteins in structural and functional genomics and also for inferring protein structure, function, and evolution. Most database search methods employ amino acid substitution matrices to score amino acid pairs. The choice of substitution matrix strongly affects homology detection performance. We earlier proposed a substitution matrix named MIQS that was optimized for distant protein homology search. Herein we further evaluate MIQS in combination with LAST, a heuristic and fast database search tool with a tunable sensitivity parameter m, where larger m denotes higher sensitivity. Results show that MIQS substantially improves the homology detection and alignment quality performance of LAST across diverse m parameters. Against a protein database consisting of approximately 15 million sequences, LAST with m = 105 achieves better homology detection performance than BLASTP, and completes the search 20 times faster. Compared to the most sensitive existing methods being used today, CS-BLAST and SSEARCH, LAST with MIQS and m = 106 shows comparable homology detection performance at 2.0 and 3.9 times greater speed, respectively. Results demonstrate that MIQS-powered LAST is a time-efficient method for sensitive and accurate homology search.

Alterations in rRNA-mRNA interaction during plastid evolution.

Translation initiation depends on the recognition of mRNA by a ribosome. For this to occur, prokaryotes primarily use the Shine-Dalgarno (SD) interaction, where the 3'-tail of small subunit rRNA (core motif: 3'CCUCC) forms base pairs with a complementary signal sequence in the 5'-untranslated region of mRNA. Here, we examined what happened to SD interactions during the evolution of a cyanobacterial endosymbiont into modern plastids (including chloroplasts). Our analysis of available complete plastid genome sequences revealed that the majority of plastids retained SD interactions but with varying levels of usage. Parallel losses of SD interactions took place in plastids of Chlorophyta, Euglenophyta, and Chromerida/Apicomplexa lineages, presumably related to their extensive reductive evolution. Interestingly, we discovered that the classical SD interaction (3'CCUCC/5'GGAGG [rRNA/mRNA]) was replaced by an altered SD interaction (3'CCCU/5'GGGA or 3'CUUCC/5'GAAGG) through coordinated changes in the sequences of the core rRNA motif and its paired mRNA signal. These changes in plastids of Chlorophyta and Euglenophyta proceeded through intermediate stages that allowed both the classical and altered SD interactions. This coevolution between the rRNA motif and the mRNA signal demonstrates unexpected plasticity in the translation initiation machinery.

Pregnancy Outcomes and Risk Factors for Uterine Rupture After Laparoscopic Myomectomy: A Single-Center Experience and Literature Review.

STUDY OBJECTIVE: To evaluate pregnancy outcomes after laparoscopic myomectomy (LSM), focusing on the risk of uterine rupture. DESIGN: Retrospective cohort study (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Of 676 women who visited the obstetrics department for a pregnancy after undergoing LSM performed at the same center between 1994 and 2012, we included the 523 women who had follow-up through the end of pregnancy. INTERVENTIONS: All patients underwent LSM, and their medical charts were retrospectively reviewed. MEASUREMENTS AND MAIN RESULTS: Multiple myomas were removed in 35.2% of cases, intramural-type lesions occurred in 46.5% of cases, and the mean myoma diameter was 4.9 cm. Pregnancy outcomes after LSM included 400 (76.5%) full-term deliveries and 100 (19.1%) vaginal deliveries, with other adverse outcomes being no different than the general population. The mean interval between LSM and pregnancy was 14 months, and only 3 (0.6%) cases of uterine rupture occurred during pregnancy. In analysis, by reviewing the published cases of uterine rupture, we found that the mean diameter, myoma number and type, and the rate of uterine suture were similar between the ruptured cases and all of our cases of LSM. CONCLUSION: LSM can be safely used in women of reproductive age who want to become pregnant. Uterine rupture occurs in rare cases, regardless of myoma features, but further large-scale studies are required to ascertain the detailed effects of various surgical techniques.

A multicenter study of the importance of systemic chemotherapy for patients with small-cell neuroendocrine carcinoma of the uterine cervix.

AIMS: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. METHODS: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. RESULTS: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. CONCLUSIONS: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.

Distribution and perinatal transmission of bacterial vaginal infections in pregnant women without vaginal symptoms.

BACKGROUND: We evaluated the distribution and vertical transmission of bacterial vaginal infections in asymptomatic pregnant women. METHODS: We performed multiplex PCR on secretions collected on cervical swabs from pregnant women at over 36 weeks of gestation and on oral secretions collected from their neonates immediately after delivery. We detected sexually transmitted infections (STIs) with the following 6 species: Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Ureaplasma urealyticum. RESULTS: Infectious agents were detected in 64 of 455 pregnant women (14.1%) and in 11 neonates (2.4%). The rate of vertical transmission was 17.2% and all the infectious agents detected in neonates were concordant with those found in their mothers. U. urealyticum was the most frequently detected in the maternal genitalia, followed by M. hominis. Women who were in labor for a longer period of time had a higher risk of vertically transmitting STI agents to their neonates. CONCLUSIONS: Vertical transmission of bacterial STIs from mothers to their infants is possible at delivery and influenced by the duration of labor. STIs should be diagnosed in pregnant women to prevent vertical transmission from the mother to the infant at the time of delivery.

Large variations in bacterial ribosomal RNA genes.

Ribosomal RNA (rRNA) genes, essential to all forms of life, have been viewed as highly conserved and evolutionarily stable, partly because very little is known about their natural variations. Here, we explored large-scale variations of rRNA genes through bioinformatic analyses of available complete bacterial genomic sequences with an emphasis on formation mechanisms and biological significance. Interestingly, we found bacterial genomes in which no 16S rRNA genes harbor the conserved core of the anti-Shine-Dalgarno sequence (5'-CCTCC-3'). This loss was accompanied by elimination of Shine-Dalgarno-like sequences upstream of their protein-coding genes. Those genomes belong to 1 or 2 of the following categories: primary symbionts, hemotropic Mycoplasma, and Flavobacteria. We also found many rearranged rRNA genes and reconstructed their history. Conjecturing the underlying mechanisms, such as inversion, partial duplication, transposon insertion, deletion, and substitution, we were able to infer their biological significance, such as co-orientation of rRNA transcription and chromosomal replication, lateral transfer of rRNA gene segments, and spread of rRNA genes with an apparent structural defect through gene conversion. These results open the way to understanding dynamic evolutionary changes of rRNA genes and the translational machinery.

Magnetic resonance imaging and intraoperative frozen sectioning for the evaluation of risk factors associated with lymph node metastasis in endometrial cancer.

INTRODUCTION: To analyze the accuracy of magnetic resonance imaging (MRI) and intraoperative frozen sectioning (IFS) for predicting the low- and high-risk patients and risk factors associated with lymph node (LN) metastasis in patients with surgically staged endometrial cancer. METHODS: The medical records of 175 patients with endometrial cancer who underwent comprehensive surgical staging including pelvic and para-aortic LN dissection between January 2008 and July 2011 were retrospectively analyzed. Results of MRI and IFS of the uterus for the evaluation of risk factors were correlated with final pathology. RESULTS: Our results showed a high specificity and negative predictive value of MRI and IFS for the evaluation of myometrial invasion and cervical stromal invasion. Of the 41 patients identified as low risk by both MRI and IFS, none had pelvic or para-aortic LN metastases in the final pathology. CONCLUSIONS: The results indicate that MRI and IFS may be useful for the evaluation of risk factors associated with LN metastasis in patients with endometrial cancer. Magnetic resonance imaging and IFS can be used to accurately identify low-risk patients who do not need comprehensive surgical staging and may prevent unnecessary lymphadenectomy.

Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) has been evaluated as a predictor for nodal metastasis or poor survival in endometrial adenocarcinoma. AIMS: To evaluate whether LVSI is a prognostic factor for lymph node metastasis and relapse of disease in endometrial adenocarcinoma. MATERIALS & METHODS: We retrospectively analysed the medical records of 438 women with endometrial adenocarcinoma treated by surgical staging, including pelvic and paraaortic lymph node dissection, between January 1996 and July 2011. RESULTS: One hundred sixty-three women (37.2%) were LVSI-positive and 275 (62.8%) were negative. LVSI-positive women were significantly older and showed more advanced stage, poorer differentiation, and a higher frequency of non-endometrioid histology type, myometrial invasion, and positive peritoneal cytology than LVSI-negative women. Surgeries by laparotomy rather than laparoscopy and more adjuvant therapies were conducted in LVSI-positive women. The median number of pelvic and paraaortic lymph nodes removed were not different, but LVSI-positive patients showed more lymph node metastases. The LVSI-positive group also showed a higher recurrence of disease and lower survival rates than the LVSI-negative group. Negative predictive values of LVSI for lymph node metastasis and recurrence of disease were 96.4 and 97.1%, respectively. In multivariate analysis, LVSI did not influence overall or disease-free survival after adjusting for several confounding factors. CONCLUSIONS: In the cases that the nodal status has not been assessed in endometrial adenocarcinoma, the presence of LVSI may be a reasonable surrogate in addition to other risk factors, in determining the need for adjuvant therapy.

Endometrial Stromal Sarcomas: A clinico-pathological analysis of 27 patients.

OBJECTIVE: To evaluate clinico-pathological features and prognostic valuses of Endometrial stromal sarcomas (ESS) through comparison of the two grade groups (low- and high-grade disease). METHODOLOGY: We retrospectively analyzed the medical records of 27 patients who were diagnosed with ESS at a single institute between March 1988 and November 2009. Our retrospective chart review was approved by our local institutional Review Board (IRB). RESULTS: The median age of the patients was 44.0 years, the median follow-up period was 101.0 months and the 10-year survival rate was 74.2%. The median uterine weight was 215.0 gm. Twenty-three (70.4%) and four patients (29.6%) had low- and high-grade disease, respectively. As primary treatment, twenty-four (70.4%) and three patients (11.1%) underwent type I hysterectomy and type III hysterectomy, respectively. Total six cases were recurred and two cases of the six-recurred patients were distant metastasis (lung) and four cases were died of the disease. Univariate analysis revealed that the histologic grade and the uterine tumor weight were significantly related with longer disease-free survival (p=0.025 and 0.043 respectively). CONCLUSION: ESSs with high-grade or larger tumor size have to be carefully and sufficiently managed, because of its rarity and aggressive behavior. To determine the proper adjuvant treatment of ESS with high risks, further clinical data should be collected and studied.

Role of systematic lymphadenectomy in patients with intermediate to high-risk early stage endometrial cancer.

OBJECTIVE: To determine the clinical significance of systematic lymph node dissection (LND) and to better define the relevant extent of LND in intermediate- to high-risk early stage endometrial cancer (EC). METHODS: Patients who received surgery as a primary treatment of histologically confirmed EC and preoperatively considered as uterus-confined early stage disease were included in the study population. The rates of lymph node metastasis (LNM) according to the risk groups and anatomic sites were assessed. Univariate and multivariate analyses were performed to evaluate risk factors for recurrence. RESULTS: A total of 804 patients were included in the study analysis. The rates of LNM were significantly different according to the risk group; 1.2% in low-risk, 20.1% in intermediate-risk, and 30.0% in high-risk group. When assessing the rates of LNM in individual anatomic sites, positive LNs were evenly distributed throughout the pelvic and para-aortic regions. In the intermediate to high-risk EC cases, the rates of para-aortic LNM below and above inferior mesenteric artery (IMA) were 11.1% and 12.5%, respectively. On multivariate analysis, LNM was the only independent risk factor for recurrence in the intermediate to high-risk EC (hazard ratio=2.63, 95% confidence interval=1.01-6.82, p=0.047). CONCLUSION: LNM was frequently observed in intermediate- and high-risk early stage EC and it served as an independent risk factor for recurrence. When considering the similar rates of LNM between below and above IMA, nodal assessment needs to be performed up to the infra-renal level, especially for the staging purpose in high-risk EC.

Laparotomy versus laparoscopy for the treatment of adnexal masses during pregnancy.

BACKGROUND: Laparoscopy has been highlighted as an effective surgical modality for diverse pelvic organ diseases. However, its surgical and obstetric efficacy has not been fully confirmed in pregnant women because of the absence of a large comparative study. The objective of this study was to compare outcomes between laparotomy and laparoscopic surgery for adnexal masses during pregnancy. METHODS: A retrospective analysis of 262 pregnant women who underwent laparotomy or laparoscopic surgery for adnexal masses between 2000 and 2009 was performed. RESULTS: Of the 262 women, 174 (66.4%) underwent laparotomy and 88 (33.6%) underwent laparoscopic surgery for adnexal masses. The laparoscopy group had a significantly shorter mean operative time (60.7 ± 27.1 vs 69.7 ± 24.4 min, P = 0.002) and mean hospital stay (4.7 ± 1.7 vs 6.6 ± 1.3 days, P < 0.001) than the laparotomy group. In multivariate analysis, there was no significant difference between laparoscopy and laparotomy group in obstetric outcomes, including preterm delivery and miscarriage rate, after adjusting for confounding factors, such as gestational age at surgery, emergency surgery and mass size. CONCLUSIONS: The laparoscopic approach appears to offer a suitable alternative to laparotomy, which, in our setting, was associated with shorter operative times and hospital stays than laparotomy.

Risk of torsion and malignancy by adnexal mass size in pregnant women.

OBJECTIVE: To investigate risks of torsion and malignancy by adnexal mass size during pregnancy. DESIGN: Retrospective review of medical records. SETTING: General university hospital and healthcare center. POPULATION: Four hundred and seventy women who underwent surgery for adnexal masses during pregnancy between 2002 and 2009. MAIN OUTCOME MEASURES: Rate of torsion and malignancy according to mass size classified into four groups: <6, 6-10, 10-15 and ≥15 cm. RESULTS: Torsion was encountered in 55 patients (11.7%) and malignancy was confirmed in 20 (4.3%). A mass size of 6-10 cm had a significantly higher risk of torsion than a mass <6 cm (odds ratio 2.68, 95% confidence interval 1.33-5.40, p=0.006). Masses ≥15 cm had an approximately 12-fold higher risk of malignancy compared with masses <6 cm (odds ratio 12.36, 95% confidence interval 2.90-52.67, p=0.001). However, for masses of 10-15 cm, the risks of both torsion and malignancy were not higher than those of masses <6 cm. CONCLUSIONS: Risks of torsion and malignancy are not directly proportional to increasing mass size in pregnant women. Physicians should be aware of a high risk of malignancy in women with an adnexal mass of over 15 cm. However, if a mass is smaller, the size should not be considered as a single independent factor in a decision for surgery.

Primary fallopian tube carcinoma: a clinicopathological analysis of a rare entity.

BACKGROUND: The aim of this study was to evaluate the clinical and pathological features of a rare tumor, primary fallopian tube carcinoma (PFTC). MATERIALS AND METHODS: We retrospectively analyzed the medical records of 26 patients who were diagnosed with PFTC at Cheil General Hospital and Women's Healthcare Center between March 1992 and November 2009. RESULTS: Median patient age was 54.6 (range 41-69) years, and the mean follow-up period was 59.8 (range 3-200) months. Twenty-one (80.8%) patients had one or more of the following preoperative symptoms: vaginal bleeding, abdominal pain, or a palpable mass. No patient was diagnosed with PFTC preoperatively; 17 (65.4%) patients were diagnosed as having an adnexal mass, six (23.1%) had hydrosalpinx, and three (11.5%) had coexisting endometrial pathology. In seven (26.9%) cases, PFTC was missed during the operation, so an additional surgery was later performed. Ten (38.5%) patients were in stage I, two (7.7%) in stage II, 13 (50%) in stage III, and one (3.8%) in stage IV. The serous type was histologically predominant (76.9%), and most were high grade (76.9%). The 5-year survival rate was 81.7%. CONCLUSION: Primary fallopian tube carcinoma is hardly ever diagnosed preoperatively or intraoperatively due to its rarity. Our report may help surgeons by providing more information about the clinicopathological behavior of PTFC so that patients can be appropriately counseled. Further clinical studies should be performed to collect more information about this rare tumor.

Laparoscopy-assisted vaginal versus abdominal hysterectomy in endometrial cancer.

INTRODUCTION: The purpose of this study was to compare the efficacy of a laparoscopy-assisted surgical staging with a traditional laparotomy staging for the treatment of endometrial cancer. METHODS: We retrospectively analyzed the medical records of 465 patients with endometrial adenocarcinoma treated by surgery between January 1996 and December 2007. RESULTS: There were no significant differences between the laparoscopy and the laparotomy groups in age, body mass index, and histologic type. However, in the laparotomy group, grade and surgical stage were higher, the diseases were more chronic, and more postoperative adjuvant treatments were necessary. One hundred seven (76.4%) of 140 patients in the laparoscopy group and 260 (80.0%) of the 325 patients in the laparotomy group had lymphadenectomy, and the median numbers of pelvic and paraaortic lymph nodes obtained were not statistically different. The laparoscopy group showed shorter postoperative hospital stay and lower blood loss, and the operating time was also shorter than that in the laparotomy group. There was no significant difference in intraoperative or postoperative complications, and the operative technique did not influence survival rates after adjusting several confounding factors. CONCLUSIONS: Our data of 12 years with a large number of patients show no differences in complications and impacts on survival between laparoscopy and laparotomy. Laparoscopy has advantages of shorter operating time and other advantages over laparotomy previously reported. Therefore, laparoscopy can be considered a good therapeutic option for endometrial cancer.

Ovarian cancer during pregnancy: clinical and pregnancy outcome.

The aim of this study is to evaluate the clinical feature and pregnancy outcome in patients with ovarian cancer diagnosed during pregnancy. We retrospectively analyzed the medical records of 27 patients diagnosed with ovarian cancer during pregnancy at Cheil General Hospital & Women's Healthcare Center from January 1996 to December 2006. Mean age of the patients was 29.1 yr (range 23-40), and a mean follow-up period was 57 months (range 7-112 months). Of 27 patients, 15 (55.5%) had borderline malignancies, 7 (25.9%) had epithelial malignancies and 5 (18.6%) had germ cell tumors. A total of 26 patients received a conservative surgery preserving pregnancy. The mean time for surgical intervention during pregnancy was 20 weeks of gestational age. Of the 27 patients, 26 had full term delivery of a healthy baby without any congenital malformation. Only one patient with epithelial ovarian cancer had a relapse at 19 months after the first conservative operation with adjuvant chemotherapy. There were few data for managing patients with ovarian cancer diagnosed during pregnancy. This study results could help establish a guideline for management of ovarian malignancy complicating pregnancy.

Conservative treatment with progestin and pregnancy outcomes in endometrial cancer.

INTRODUCTION: The purpose of this study was to evaluate the efficacy of conservative treatment with progestin and pregnancy outcomes in women with early-stage endometrial cancer. METHODS: We retrospectively analyzed the medical records of 35 patients with endometrial adenocarcinoma, who were treated with progestin from January 1996 to December 2006. Women with early-stage grade 1 endometrioid endometrial adenocarcinoma, who wanted to receive conservative treatment or preserve fertility, were included. All women were treated with medroxyprogesterone acetate or megestrol acetate, with regular dilation and curettage performed. Complete remission (CR) was defined as no evidence of endometrial adenocarcinoma or hyperplasia. Partial remission was diagnosed when the patient developed endometrial hyperplasia, and persistent disease was defined as residual endometrial adenocarcinoma by pathologic confirmation. RESULTS: The median age was 31 years (range, 21-43 years), and the median follow-up period was 39 months (range, 5-108 months). Complete remission was achieved in 22 patients (62.9%), partial remission was achieved in 1 patient (2.9%), and 12 patients (34.3%) had persistent disease. The median time to CR was 9 months (range, 2-12 months). Of the 22 patients with CR, 9 (40.9%) had recurrent disease, and the median time to recurrence was 12 months (range, 8-48 months). Ten (83.3%) of the 12 patients with CR who tried to conceive were successful, and 8 of the 10 pregnancies resulted in live births. There were no congenital anomalies in babies associated with progestin treatment. CONCLUSIONS: Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.

Toxicity of intraperitoneal chemotherapy and risk factors for severe toxicity in optimally debulked ovarian cancer patients.

OBJECTIVE: To assess the effect and toxicity of intraperitoneal (IP) chemotherapy for epithelial ovarian cancer and to determine the risk factors for severe toxicity. MATERIALS AND METHODS: Patients who received IP chemotherapy after optimal debulking surgery for ovarian cancer between 2006 and 2012 were retrospectively reviewed. Clinical characteristics were compared between patients with none/Grade 1 or Grade 2 toxicity and those with Grade 3 or Grade 4 toxicity. RESULTS: In 41 patients, the mean number of IP cycles administered was 5.6 and most patients (80.5%) completed at least six cycles. The reasons for discontinuation were catheter-related problems (30%), disease progression (20%), or drug-related adverse effects (30%). Grade 3 or Grade 4 toxicity was observed in 30 patients (73.2%). The rate of neoadjuvant chemotherapy was higher in the patients with Grade 3 or Grade 4 toxicity (37%) than in the patients without Grade 3 or Grade 4 toxicity (9%), however, this difference was not significant (p = 0.128). During a mean follow-up period of 33.6 months, tumor recurrence occurred in 20 (48.8%) patients and the median progression-free survival was 30.0 months. CONCLUSION: Despite the high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer. Toxicity should be closely monitored in patients who have received neoadjuvant chemotherapy until a large prospective study can be performed to determine its influence.