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This paper presents a new description of the morphology of the planktonic dinoflagellate Stoeckeria algicida n. gen., n. sp. and a report of the sequence of the small subunit rDNA (SS rDNA) from cultured cells. The vegetative biflagellated cell, gametes, triflagellated planozygotes, and cyst stages of this heterotrophic species were observed in cultures. The vegetative biflagellated cells are oval, with the cell length being considerably larger than the cell width. The ranges (and mean, n=60) of cell length and width of live biflagellated cells satiated with the raphidophyte Heterosigma akashiwo were 14.4-20.8 microm (16.8) and 10.0-17.4 microm (12.9), respectively, while those of biflagellated cells starved for 3 d (n=60) were 7.3-15.9 microm (11.6) and 2.7-12.2 microm (7.3), respectively. Thin plates of the vegetative biflagellated cells were arranged in a Kofoidian series of Po, cp, X, 4', 2a, 7'', 6c, 6s, 5''', 0 (p), and 2''''. When properly aligned, the sequence of the SS rDNA of the biflagellated cells of S. algicida (GenBank Accession no. AJ841809) was 3% different from that of a dinoflagellate from Shepherd's Crook and 4% different from that of Cryptoperidiniopsoid sp. brodyi, Pfiesteria spp., or Pfiesteria-like species. In a maximum-likelihood-distance phylogenetic tree generated using the SS rDNA sequences, Pfiesteria spp., Pfiesteria-like species, and a dinoflagellate from Shepherd's Crook were closest to S. algicida, but these dinoflagellates were clearly divergent with S. algicida. Based on morphological and genealogical analyses, we suggest that this is a new species in a new genus.

The red-tide dinoflagellate Gonyaulax polygramma (GenBank accession number = AJ833631), previously known as an exclusively autotrophic dinoflagellate, has been found to be a mixotrophic species. We investigated feeding mechanisms, types of prey species, and the effects of prey concentration on the growth and ingestion rates of G. polygramma when feeding on an uniden- tified cryptophyte species (equivalent spherical diameter, ESD = 5.6 µm). We also calculated grazing coefficients by combining field data on abundances of G. polygramma and co-occurring cryptophytes with laboratory data on ingestion rates obtained in the present study. Among the phytoplankton prey offered, G. polygramma ingested small phytoplankton species with ESD ≤ 17 µm, but did not feed on large phytoplankton species with ESD > 22 µm. G. polygramma fed on prey cells by engulfing them through the apical horn, a previously unknown mechanism, as well as through the sulcus. The feed- ing mechanism of G. polygramma on phytoplankton mainly depended on the prey species. Specific growth rates of G. polygramma on a cryptophyte increased with increasing mean prey concentration, with saturation occurring at a mean prey concentration of approximately 600 ng C ml -1 . The maxi- mum specific (mixotrophic) growth rate of G. polygramma on a cryptophyte was 0.278 d -1 , under a 14:10 h light:dark cycle of 50 µE m -2 s -1 , while its (phototrophic) growth rate under the same light conditions without added prey was 0.186 d -1 . Its maximum ingestion and clearance rates were 0.18 ng C grazer -1 d -1 (10.6 cells grazer -1 d -1 ) and 0.18 µl grazer -1 h -1 , respectively. The grazing coefficients of G. polygramma on cryptophytes were up to 0.479 h -1 . The results of the present study suggest that G. polygramma can have a considerable grazing impact on cryptophyte populations.

This study was designed to establish a more effective and safe culture system for adoptive immunotherapy by investigating the use of homologous cord blood plasma (HCBP) instead of fetal bovine serum (FBS), which has various limitations including ethical problems for the ex vivo expansion of human umbilical T lymphocytes. Fresh human umbilical mononuclear cell fractions were isolated by Ficoll-Hypaque density centrifugation. Nonadherent mononuclear cell fractions were cultured with anti-CD3 antibody (5 microg/ml), IL-2 (175 U/ml), and either 10% FBS or 10% HCBP. On day 8, the cellular proliferation rate and cell surface markers were assessed. There was no significant difference in proliferation when human umbilical cord blood T lymphocytes were grown in medium supplemented with FBS or HCBP (p0.05). In medium containing FBS, the proportion of CD3(+)CD4(+) (markers for helper T cell), CD3(+)CD8(+) (cytotoxic T cell), CD3(+)CD25(+) (activated T cell), CD3(+)CD38(+) (immature T cell), and CD3(+)CD45RO(+) (memory T cell) cells was significantly increased (p0.05), whereas proportion of CD3(+)CD45RA(+) (naive T cell) and CD16(+)CD56(+) (NK cell) cells was significantly decreased (p0.05). In HCBP supplemented medium, the proportion of CD3(+)CD8(+), CD3(+)CD25(+), CD3(+)CD45RA(+), and CD3(+)CD45RO(+) cells was significantly increased (p0.05). The proportion of CD3(+)CD4(+), CD3(+)CD45RO(+) and CD3(+)CD38(+) cells was significantly higher, but proportion of CD3(+)CD45RA(+) and CD3(+)CD8(+) cells was significantly lower in FBS compared with HCBP supplemented medium (p0.05). Our results support the feasibility of ex vivo expansion of human umbilical cord blood T lymphocytes in medium supplemented with HCBP for future adoptive cellular immunotherapy.

To investigate the roles of the newly described thecate heterotrophic dinoflagellate Stoeckeria algicida (GenBank accession number = AJ841809), which was abundant during the red tides dominated by the harmful raphidophyte Heterosigma akashiwo, we measured the abundances of H. akashiwo and S. algicida in Masan Bay, Korea, from May to July 2004. We also measured growth and ingestion rates of S. algicida when feeding on H. akashiwo in the laboratory. Grazing coefficients were calculated by combining field data on abundances of S. algicida and co-occurring H. akashiwo with laboratory data on ingestion rates obtained in the present study. The maximum abundances of H. akashiwo during 2 H. akashiwo red tides were 58 400 and 99 200 cells ml, while those of S. algicida were 1130 and 17 400 cells ml -1 , respectively. The time lags between the abun- dance peaks of H. akashiwo and S. algicida in these red tide periods were 1 to 2 d. S. algicida fed on H. akashiwo using a peduncle after anchoring the prey by a tow filament. Specific growth rates of S. algicida increased rapidly with increasing mean prey concentration before saturating at H. akashiwo concentrations of ca. 350 ng C ml -1 (3500 cells ml -1 ). The maximum specific growth rate of S. algicida on H. akashiwo was 1.63 d -1 . The threshold prey concentration (where net growth = 0) was 1.9 ng C ml -1 (19 cells ml -1 ). Maximum ingestion and clearance rates of S. algicida on H. akashiwo were 0.75 ng C grazer -1 d -1 (7.5 cells grazer -1 d -1 ) and 3.7 μl grazer -1 h -1 , respectively. Calculated grazing coefficients for S. algicida on H. akashiwo were up to 0.142 min -1 (i.e. 13% of H. akashiwo populations were removed by a S. algicida population in 1 min). The results of the pre- sent study suggest that S. algicida sometimes has a considerable grazing impact on populations of H. akashiwo.

Hemiasterlins are sponge-derived tripeptides that inhibit cell growth by depolymerizing existing microtubules and inhibiting microtubule assembly. Since hemiasterlins are poor substrates for P-glycoprotein, they are attractive candidates for cancer therapy and have been undergoing clinical trials. The basis of resistance to a synthetic analogue of hemiasterlin, HTI-286 (HTI), was examined in cell populations derived from ovarian carcinoma (A2780/1A9) cells selected in HTI-286. 1A9-HTI-resistant cells (1A9-HTI(R) series) were 57-89-fold resistant to HTI. Cross-resistance (3-186-fold) was observed to other tubulin depolymerizing drugs, with collateral sensitivity (2-14-fold) to tubulin polymerizing agents. Evaluation of the percentage of polymerized and soluble tubulin in 1A9 parental and 1A9-HTI(R) cells corroborated the HTI cytotoxicity data. At 22 degrees C or 37 degrees C, in the absence of any drug, the percentage of polymerized microtubules for each of the 1A9-HTI(R) populations was greater than that in the 1A9 parental cells, consistent with more stable microtubules. Furthermore, microtubules in the 1A9-HTI(R) populations were also more resistant to depolymerization at 4 degrees C and had more acetylated and detyrosinated (Glu-tubulin) alpha-tubulin, all characteristic of more stable microtubules. The 1A9-HTI(R) cell populations exhibited either a single nucleotide change in the M40 beta-tubulin isotype, S172A, or in two cell populations where no beta-tubulin mutation was detected, mutations in the Kalpha-1 alpha-tubulin isotype, S165P and R221H in one resistant cell population and I384V in another. Unlike reports of mutations resulting in reduced drug affinity, the experimental data and location of mutations are consistent with resistance to HTI-286 mediated by microtubule-stabilizing mutations in beta- or alpha-tubulin.

We first reported here that the harmful alga Cochlodinium polykrikoides, which had been previously known as an autotrophic dinoflagellate, was a mixotrophic species. We investigated the kinds of prey species and the effects of the prey concentration on the growth and ingestion rates of C. polykrikoides when feeding on an unidentified cryptophyte species (Equivalent Spherical Diameter, ESD = 5.6 microm). We also calculated grazing coefficients by combining field data on abundances of C. polykrikoides and co-occurring cryptophytes with laboratory data on ingestion rates obtained in the present study. Cocholdinium polykrikoides fed on prey cells by engulfing the prey through the sulcus. Among the phytoplankton prey offered, C. polykrikoides ingested small phytoplankton species that had ESD'sor = 11 microm (e.g. the prymnesiophyte Isochrysis galbana, an unidentified cryptophyte, the cryptophyte Rhodomonas salina, the raphidophyte Heterosigma akashiwo, and the dinoflagellate Amphidinium carterae). It did not feed on larger phytoplankton species that had ESD'sor = 12 microm (e.g. the dinoflagellates Heterocapsa triquetra, Prorocentrum minimum, Scrippsiella sp., Alexandrium tamarense, Prorocentrum micans, Gymnodinium catenatum, Akashiwo sanguinea, and Lingulodinium polyedrum). Specific growth rates of C. polykrikoides on a cryptophyte increased with increasing mean prey concentration, with saturation at a mean prey concentration of approximately 270 ng C ml(-1) (i.e. 15,900 cells ml(-1)). The maximum specific growth rate (mixotrophic growth) of C. polykrikoides on a cryptophyte was 0.324 d(-1), under a 14:10 h light-dark cycle of 50 microE m(-2) s(-1), while its growth rate (phototrophic growth) under the same light conditions without added prey was 0.166 d(-1). Maximum ingestion and clearance rates of C. polykrikoides on a cryptophyte were 0.16 ng C grazer(-1)d(-1) (9.4 cells grazer(-1)d(-1)) and 0.33 microl grazer(-1)h(-1), respectively. Calculated grazing coefficients by C. polykrikoides on cryptophytes were 0.001-0.745 h(-1) (i.e. 0.1-53% of cryptophyte populations were removed by a C. polykrikoides population in 1 h). The results of the present study suggest that C. polykrikoides sometimes has a considerable grazing impact on populations of cryptophytes.

Aims . There are few studies reporting survival or recurrence patterns in colorectal cancer patients with inferior mesenteric lymph node metastasis (IMLN+). The present study evaluated the prognostic significance of patients being IMLN+ or IMLN− in colorectal cancer. Methods . Survival, recurrence pattern and treatment protocols were compared between 63 IMLN+ patients and 108 IMLN− patients with stage III and IV rectal and sigmoid cancer undergoing curative surgery. Lymph node sampling was routinely performed prior to inferior mesenteric artery ligation and excision flush with aorta. Limited principal node dissection including IMLN was performed in cases of identified node metastasis. Results . The 5-year disease-free survival rates were 50% in IMLN− and 31% in IMLN+ patients ( P =0.004). The 5-year disease-free survival rate was greater in the N1 group than the N2 group ( P =0.038). Cox regression analysis showed IMLN+, lymphovascular tumour invasion, T4, M1, and pre-operative serum CEA level over 6 ng/ml were independently associated with unfavorable disease-free survival. The prognostic significance of M category was greater when the IMLN+ was included in the M1 as opposed to the N category. In patients undergoing absolute curative surgery, post-operative recurrence rates were 34% for IMLN− and 57% for IMLN+ patients ( P =0.009; OR, 2.611; 95% CI, 1.313–5.194). For IMLN+ patients, post-operative adjuvant treatment independently correlated with disease-free survival ( P =0.029). Conclusions . IMLN+ is an independent survival factor enhancing the prognostic significance of the M category in the AJCC staging. Curative radical surgery and post-operative chemoradiotherapy appears to be warranted for IMLN+ colorectal cancer patients as it resulted in 5-year disease-free survival rates of up to 31% compared to 50% in IMLN− patients.

To investigate the interactions between the ciliate Strombidinopsis jeokjo and the heterotrophic dinoflagellates Gyrodinium dominans and Oxyrrhis marina, we measured the growth and ingestion rates of S. jeokjo (mean length and width of fixed specimens = 149 × 70 µm, n = 30) when feeding on each of the heterotrophic dinoflagellates, and calculated grazing coefficients by combining field data on abundances of large Strombidinopsis spp. (>100 µm in length) and co- occurring heterotrophic dinoflagellates with laboratory data on ingestion rates obtained in the pre- sent study. The specific growth rates of S. jeokjo when feeding on G. dominans and O. marina increased rapidly with increasing prey concentration (ca.

PURPOSE A prospective, randomized phase III, clinical trial was performed to assess treatment related acute toxicity, early response and survival difference, between a monthly 5-FU cisplatin, and a weekly cisplatin group alone, for concurrent chemoradiotherapy in the locally advanced uterine cervical carcinoma patients. MATERIALS AND METGODS: Between March 1998 and March 2000, 35 patients, with locally advanced (FIGO stage IIB to IVA) cervical carcinoma, were studied, but 5 patients were excluded inform the analysis due to their refusal of treatment. The patients were randomly assigned to 'monthly 5-FU cisplatin' (arm I), or 'weekly cisplatin' (arm II), groups. The patients of arm I received 5-FU cisplatin (5-FU 1,000 mg/m2/day cisplatin 20 mg/m2/day, IV continuous infusion, for 5 days, 3 cycles with 4-week intervals) with radiation therapy. Those of arm II received only cisplatin (cisplatin 30 mg/m2/day, IV bolus, 6 cycles with 1-week intervals) with radiation therapy. The radiation therapy consisted of external beam irradiation of 41.4~50.4 Gy/23~28 fractions, and high dose rate intracavitary treatments, delivering a dose of 30~35 Gy to point A in 6~7 fractions. During intracavitary radiation, a parametrial boost was delivered for a point B dose of 60 Gy in the non-thickened side, and 65 Gy in the thickened side. Treatment related acute toxicities were assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. The response to treatment, and survival, were analyzed. The median follow-up period was 19 months. RESULTS The FIGO stage distributions of arm I (n=16) and arm II (n=14) were as follows; IIB 10, IIIA 1, IIIB 4, IVA 1 in arm I, 12, 0, 1 and 1 in arm II respectively. The compliance of both arms were 80.0% and 93.3%, respectively (p=0.37). During radiation therapy, the incidences of leukopenia, greater than RTOG grade 2, were 25.0%, 14.3%, respectively. There were no patients with gastrointestinal or genitourinary toxicity greater than RTOG grade 2. The complete response rates at 3 months, following radiation therapy, were 87.5% and 92.9% respectively. Two-year disease free survival rates were 81.3%, 85.7%, respectively, for each arms. CONCLUSION There was no significant difference in response to treatment, or patterns of failure, between the monthly FP and weekly cisplatin arms. Although there were no statistically significant differences, the patients of the weekly cisplatin arm had better compliance. More patients, and a longer follow up, are needed for improved evaluation of the regimen.

5578 Background: In experimental studies, adrenergic hormones are involved in tumorigenesis of ovarian cancer and its progression. We investigated the impact of beta adrenergic blocker on survival outcome of ovarian cancer since few studies have investigated its relevance. Methods: Data of Korean National Health Insurance Service was analyzed (n = 866). We analyzed the impact of beta blocker on survival outcome of ovarian cancer according to the duration on medication and age groups of patients. Cox proportional hazards regression was used to analyze hazard ratios (HR) for all-cause mortality with 95% confidence intervals (CI) adjusting for confounding factors. Results: Median years of follow-up was 5.98 and 6.71 for non-users and users, respectively. Among the 866 patients, 206 (23.8%) were users and 660 (76.2%) were non-users. In total, there was no survival difference between the 2 groups. But, when patietns were grouped according to the duration of medication, patients with longer duration of medication (≥1 year) showed better survival outcome (adjusted HR 0.305 [95% CI: 0.187-0.500], P < 0.001). Also, beta blocker use in patients with > 60 years showed better survival compared to younger patients (adjusted HR 0.579 [95% CI: 0.408-0.822], P = 0.002). In patients with > 60 years, medication longer than 720 days was associated with better survival outcome (adjusted HR 0.267 [95% CI: 0.140-0.511], P < 0.001). Both selective and non-selective beta blocker showed identical survival benefit in these settings without difference between each other. Conclusions: Beta blocker medication was associated with favorable survival outcome in ovarian cancer, especially when used in older patients and in long term duration.

e15778 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, erlotinib, and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically proven locally advanced, recurrent or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine at 1,000 mg/m2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on days 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2was permitted from second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1–8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.

Supplemental Digital Content is available in the text, To identify prognostic factors for overall survival after recurrence (OSr) in endometrioid endometrial cancer (EC) patients and categorize patient subgroups that predict outcomes using these variables. Consecutive patients with recurrent endometrioid EC seen in our institution from 1989 to 2013 were retrospectively reviewed. Cox regression models were used to identify the clinicopathological factors associated with OSr. By summing scores proportionate to the hazard ratio (HR) for each significant variable, we stratified patients into 3 risk groups. Enrolled patients (n = 108) had a median time to recurrence of 15 (range, 3–163) months after initial treatment and a median OSr of 22 (range, 1–207) months. Twenty patients (18.5%) had locoregional recurrence, and 88 (81.5%) distant. One hundred three patients underwent salvage therapy; 51 (47.2%) received chemotherapy only, 22 (20.3%) received radiotherapy either alone or combined with chemotherapy, and 29 (26.9%) underwent salvage cytoreductive surgery. Multivariate regression analysis revealed that time to relapse after initial treatment, cancer antigen-125 level at recurrence, and the number of recurrent lesions were independent predictors of OSr. Incorporating these factors, we stratified patients into low-risk (n = 19), intermediate-risk (n = 43), and high-risk (n = 46) groups. The likelihood of cancer-specific death was higher in both the high-risk (HR = 8.948, 95% confidence interval [CI] = 3.498–22.893, P

476 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, erlotinib, and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically proven locally advanced, recurrent or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine at 1,000 mg/m2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on day 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1–8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 31 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The overall response rate was 12.9% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 74.2% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.4 months (95 % CI, 2.3-4.5 months) and 5.7 months (95 % CI, 3.9-7.6 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.

OBJECTIVE This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. METHODS This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m2) between 1st December 2014 and 31th July 2016. RESULTS The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P

To estimate the efficacy of laparoendoscopic single-site (LESS) ovarian cystectomy in ovarian endometrioma.Retrospective study. Canadian Task Force Classification II-2.University hospital.Three hundred forty-three premenopausal women with previously untreated ovarian endometrioma.The surgical and follow-up outcomes were compared between LESS (n = 154) and conventional laparoscopic ovarian cystectomy (n = 189).Four patients (2.6%) in the LESS group but no patients in conventional group required additional ports (p = .040). No patient in either group required conversion to laparotomy. Operating times, estimated blood loss, perioperative hemoglobin level changes, and transfusions did not differ between groups. However, the length of postoperative hospital stay was significantly shorter in the LESS group (2 ± .4 days vs 2.3 ± .8 days, p = .001) and significantly more patients in this group were discharged within 2 days of surgery (93.5% vs 79.4%, p.001). Perioperative complications occurred in 1 patient (0.6%) in the LESS group and in 2 patients (1.1%) in the conventional group (p.999). The LESS group showed significantly lower pain scores at 16 (3.2 vs 3.6, p.001), 24 (2.8 vs 3, p = .004), and 30 hours (2.7 vs 3, p = .040) after surgery. The requirement for additional analgesics was significantly lower in the LESS group (27.9% vs 45%, p = .001). After a median follow-up time of 48 months, 11 patients (7.1%) in the LESS group and 21 patients (11.1%) in the conventional group showed recurrent endometrioma (p = .209).LESS ovarian cystectomy has similar feasibility and efficacy with conventional laparoscopic surgery in the management of endometrioma. However, LESS is associated with less postoperative pain, lower analgesic requirement, and earlier discharge.

The aim of this study was to find anatomical landmarks for rotational alignment of the tibial component in total knee replacement (TKR) in a CT-based study. Pre-operative CT scanning was performed on 94 South Korean patients (nine men, 85 women, 188 knees) with osteoarthritis of the knee joint prior to TKR. The tibial anteroposterior (AP) axis was defined as a line perpendicular to the femoral surgical transepicondylar axis and passing through the centre of the posterior cruciate ligament (PCL). The angles between the defined tibial AP axis and anatomical landmarks at various levels of the tibia were measured. The mean values of the angles between the defined tibial AP axis and the line connecting the anterior border of the proximal third of the tibia to the centre of the PCL was -0.2° (-17 to 14.1, sd 4.1). This was very close to the defined tibial axis, and remained so regardless of lower limb alignment and the degree of tibial bowing. Therefore, AP axis defined as described, is a reliable anatomical landmark for rotational alignment of tibial components.Cite this article: Bone Joint J 2014; 96-B:1485–90.

Background Anterior gradient 2 (AGR2) has been implicated in tumor-associated phenotypes such as cell viability, invasion and metastasis in various human cancers. However, the tumor promoting activity of AGR2 has not yet been determined in biliary tract cancers. Thus, we examined the expression of AGR2 and its tumor-promoting activity in biliary tract cancer cells in this study. Methods Expression of AGR2 mRNA and protein was analyzed by real time RT-PCR and western blotting, respectively. MTT assay was employed to measure cell viability and pulsed BrdU incorporation by proliferating cells was monitored by flow cytometry. Soft agar colony formation assay and transwell invasion assay were employed to determine anchorage-independent growth and in vitro invasion of the tumor cells, respectively. In vivo tumor formation was examined by injection of tumor cells into immunocompromised mice subcutaneously. Statistical analysis was performed with 2-tailed unpaired Student’s t-test for continuous data and with one-way ANOVA for multiple group comparisons. Bonferroni tests were used for post hoc 2-sample comparisons. Results AGR2 mRNA was detected in SNU-245, SNU-478, and SNU-1196 cell lines, and its protein expression was confirmed in SNU-478 and SNU-245 cell lines by western blot analysis. Knockdown of AGR2 expression with an AGR2-specific short hairpin RNA (shRNA) in SNU-478, an ampulla of Vater cancer cell line resulted in decreased cell viability and in decreased anchorage-independent growth by 98%. The AGR2 knockdown also increased the sensitivity of the cells to chemotherapeutic drugs, including gemcitabine, 5-fluorouracil and cisplatin. In addition, SNU-478 cells expressing AGR2-shRNA failed to form detectable tumor xenografts in nude mice, whereas control cells formed tumors with an average size of 179 ± 84 mm3 in 3 weeks. Overexpression of AGR2 in SNU-869 cells significantly increased cell viability through enhanced cell proliferation and the number of Matrigel™-invading cells compared with AGR2-negative SNU-869 cells. Conclusions Our findings implicate that AGR2 expression augments tumor-associated phenotypes by increasing proliferative and invasive capacities of the ampulla of Vater cancer cells.

Upper gastrointestinal bleeding (UGIB) leads to significant morbidity and mortality in chronic kidney disease (CKD) patients. This study determined the efficacy of using a low-dose proton pump inhibitor (PPI) to reduce the risk of non-variceal UGIB in CKD patients receiving aspirin.We retrospectively reviewed the medical records of 500 CKD patients who received aspirin between January 2008 and March 2013. Cumulative incidence analysis using the Kaplan-Meier method was performed to analyze the rate of non-variceal UGIB and association with the administration of low-dose PPI.Of the 500 patients, 191 received low-dose PPI. Over the follow-up period, which lasted 1067 person-years, three patients in the low-dose PPI group (8.9 per 1000 person-years) and 19 patients in the non-PPI group (25.9 per 1000 person-years) developed non-variceal UGIB, respectively (P = 0.113). Low-dose PPI use did not decrease the risk of UGIB in CKD patients, including patients who did not receive dialysis (P = 0.127). However, according to the subgroup analysis of 230 patients who received dialysis, the low-dose PPI group (14.4 per 1000 person-years) demonstrated significantly reduced incidence and risk of non-variceal UGIB in comparison with the non-PPI group (53.8 per 1000 person-years) (P = 0.032).Prophylactic low-dose PPI can reduce the risk of non-variceal UGIB in dialysis patients receiving aspirin.

An actual gas mixer features that a single gas outlet pressure will be raised if the mixed gas output flow is smaller than the single gas output flow when mixing takes place, and if it is raised to the operating limit of flow regulator, some part of the total flow of mixed gas output will be decreased, and the flow will be decreased from the smallest input pressure among gas elements of the mixed gas. This feature causes errors in mixing proportion.

Objective To compare outcomes after radical hysterectomy in patients with stage IB1 adenocarcinoma (AdCa) and adenosquamous carcinoma (AdSCCa) of the uterine cervix. Methods We performed a retrospective analysis of 265 patients with AdCa and 72 patients with AdSCCa. Demographic, clinicopathologic, surgical, and follow-up data were compared. Results There were no differences in demographic and clinicopathologic characteristics between the two histologic types (AdCa vs. AdSCCa). Only mean size of tumor and lymphovascular space invasion was larger and more frequent in AdSCCa (2.7cm vs 2.3cm, P=0.019 & 29.2% vs 14.7%, P=0.008). After a median follow-up time of 68months, 39 (14.7%) and 13 (18.1%) AdCa and AdSCCa patients, respectively, had recurrent disease (P=0.467), and 33 (12.5%) and 11 (15.3%) patients, respectively, died of their disease (P=0.555). 5-year RFS rates were 89% and 85% (P=0.582), respectively, and 5-year OS rates were 93% and 89% (P=0.787). Histologic type had no clinical impact on RFS and OS in multivariate analysis adjusting for significant prognostic factors. There were no differences in pattern of recurrence and time to recurrence between the two histologic types. When patients were stratified into three risk groups according to the criteria of GOG protocols 92 and 109, histologic type had no clinical impact on RFS and OS in any of the risk groups. Conclusion There are no differences in clinicopathologic factors, patterns of recurrence, time to recurrence, RFS and OS between patients with AdCa and AdSCCa.

The aim of this study was to assess the therapeutic effect of mosapride in patients with functional dyspepsia (FD).Randomized controlled trials (RCTs) of mosapride for the treatment of FD performed between 2002 and 2013 were identified from databases. Symptom response rates were extracted and analyzed using risk ratios (RRs). A random effect model was applied based on Higgins I(2) tests. Publication bias was evaluated using a funnel plot, Egger's test, trim and fill, and the rank correlation test.In total, 13 RCTs, which included 1091 mosapride-treated patients and 1129 control patients (on placebo or other drugs), were identified and analyzed. Overall, mosapride showed an RR of 0.999 (95% confidence interval [CI]: 0.869-1.150, P = 0.992) for improving global efficacy or symptom-based scores. In a sensitivity analysis of the high-quality RCTs, mosapride showed an RR of 1.114 (95% CI: 1.011-1.227, P = 0.029). However, in the studies using the Rome III criteria for the diagnosis of FD, mosapride showed an RR of 0.906 (95% CI: 0.807-1.016, P = 0.092). In the studies having funding source, mosapride showed an RR of 1.131 (95% CI: 1.028-1.244, P = 0.012), whereas an RR of 0.966 (95% CI: 0.896-1.042, P = 0.367) was observed in the studies without funding source. Publication bias was not detected.In this analysis, we could not find a significant effect of mosapride on FD. Inconsistent diagnostic criteria for FD and different assessment outcomes are causes of heterogeneity. Further studies using common validated outcomes or questionnaires and high-quality RCTs will elucidate the real effect of this medication on FD.

IL-34 is a recently identified alternative ligand for colony-stimulating factor-1 (CSF-1) receptor. IL-34 and CSF-1 are regulators of differentiation, proliferation, and survival in mononuclear phagocytes. Here, we investigated the IL-34 serum concentration and expression in human adipose tissues and any associations with insulin resistance.We recruited 19 nondiabetic obese women, 9 type 2 diabetic women, and 27 normal-weight women. Metabolic parameters, abdominal fat distribution, serum IL-34 concentration, and IL-34 mRNA expression were measured in abdominal sc adipose tissue (SAT) and visceral adipose tissue (VAT). In addition, the expression/secretion and putative effects of IL-34 were assessed in human differentiated adipocytes. Serum IL-34 concentration was measured before and 5 to 9 months after laparoscopic Roux-en-Y gastric bypass surgery was performed on the 20 obese patients.Regardless of diabetes status, obese patients demonstrated significantly higher serum IL-34 concentrations than controls. Serum IL-34 was significantly and positively correlated with insulin resistance-related metabolic parameters. IL-34 mRNA was significantly higher in VAT than SAT. IL-34 was expressed in adipocytes as well as nonadipocytes, and expression was significantly higher during adipogenesis. In differentiated adipocytes, the expression/secretion of IL-34 was enhanced by TNFα and IL-1β. In addition, IL-34 augmented fat accumulation and inhibited the stimulatory effects of insulin on glucose transport. Moreover, serum IL-34 was significantly decreased after Roux-en-Y gastric bypass-induced weight loss.The present study demonstrates, for the first time, that IL-34 is expressed in human adipose tissues and the circulating concentration is significantly elevated in obese patients. This suggests that IL-34 is associated with insulin resistance.

To evaluate the prognostic factors of ovarian granulosa cell tumors (GCTs) and treatment outcomes in recurrent GCT cases.We retrospectively reviewed 91 patients with GCT who were treated in two tertiary Centers between 1989 and 2011.Eighty patients had stage I tumors, five had stage II, and six had stage III. There were 15 cases of recurrence with a median follow-up time of 58 (3-254) months. Multivariate analysis identified greater tumor size and postoperative residual tumor as independent risk factors for recurrence. Twelve patients underwent secondary surgery at first recurrence. At a median follow-up of 50 (4-185) months from first recurrence, the 5-year survival was 60% for patients with and 100% for those without residual tumor after secondary surgery, respectively (p=0.018, log-rank test).Complete cytoreduction is an important prognostic factor for recurrent cases as well as initial treatment of GCT.

To evaluate the long-term outcomes and risk factors for recurrence after fertility-sparing laparoscopic radical trachelectomy (LRT) in young women with early-stage cervical cancer.Eighty-eight consecutive patients from four tertiary cancer centers in Korea who had attempted fertility-sparing LRT for early-stage cervical cancer were included in this study.Seventy-nine patients completed LRT. The mean age and tumor size were 31 years (range, 20-40 years) and 1.8 cm (range, 0.4-7 cm), respectively. Twenty-nine patients had a tumor size greater than 2 cm, 22 had deep stromal invasion greater than 50%, and twelve had lymphovascular space invasion. After a median follow-up time of 44 months (range, 3-105 months), nine patients had recurrence and one had died of disease. A tumor size greater than 2 cm (P = 0.039) and a depth of stromal invasion greater than 50% (P = 0.016) were significant risk factors for recurrence.This is the largest series on fertility-sparing LRT in young women with early cervical cancer. LRT is a feasible and safe fertility-sparing alternative to radical hysterectomy in these women. A tumor size greater than 2 cm and a depth of stromal invasion greater than 50% were risk factors for recurrence.

The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.

We describe two cases of malignant lymphoma presenting as inflammatory nodules of the leg and mimicking panniculitis clinically. In both cases the skin biopsies showed prominent involvement of the subcutaneous tissue by lymphoma cells. In addition, lymphoma cells invaded blood vessels in the dermis or the subcutaneous tissue. One case was characterized by predominantly extravascular and intravascular location of the lymphoma cells, and the other case by the predominantly extravascular and intramural location of lymphoma cells. These histological findings were compatible with those of angiocentric T-cell lymphoma but with some unusual features. Angiocentric T-cell lymphoma of the skin should be listed in the group of diseases which present as inflammatory nodules of the leg.

Corrosive esophagitis is characterized by caustic injury due to the ingestion of chemical agents, mainly alkaline substances such as detergents. Esophageal bleeding, perforation, or stricture can be worsened by high-degree corrosive esophagitis. Picosulfate is a commonly used laxative frequently administered for bowel preparation before colonoscopy or colon surgery. Picosulfate powder should be completely dissolved in water before ingestion because the powder itself may cause chemical burning of the esophagus and stomach. Here, we report a case of corrosive esophagitis due to the ingestion of picosulfate powder that was not completely dissolved in water.

To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of 1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but 1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival.Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild.Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

This study aimed to prospectively correlate clinical outcomes of advanced epithelial ovarian cancer (AEOC), with the results of in vitro chemosensitivity testing of taxol and carboplatin using the in vitro histoculture drug response assay (HDRA). A total of 104 patients with AEOC were treated with combination chemotherapy of taxol and carboplatin after primary cytoreductive surgery between 2007 and 2012 at the Asan Medical Center, Seoul, Korea. To compare chemosensitivity in the HDRA with clinical response, all patients were first categorized into two groups as either sensitive to both taxol and carboplatin (SS), or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group; 29.2% vs 69.8%, respectively (p=0.02). The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs 16.0 months, respectively (p=0.025). These results demonstrate that the HDRA prospectively correlates to clinical outcome from chemotherapy and that treatment regimens can be individualized based on the HDRA.

The application of pelviscopic surgery for the management of ovarian tumors has increased dramatically in the last few years. Of particular concern is the pelviscopic excision of malignant ovarian tumors. One of the important potential problems with this approach is disseminating malignant cells to peritoneal surface. The aim of this report is to draw attention to the possibility of the occurrence of a tumor implantation at the pelviscopic port site in patients with malignant ovarian tumors. A case is presented here in which a localized tumor implant occurred in the abdominal trocar site after pelviscopic removal of ovarian mass subsequently found to be squamous cell carcinoma arising in mature cystic teratoma with brief review of literatures.

AIM To identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs). METHODS Between June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts. RESULTS We observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P < 0.001). Two endoscopic methods were studied, including endoscopic submucosal resection with a ligation device and endoscopic submucosal dissection, and no statistically significant difference in the LVI detection rate was detected between the two (26.3% and 26.8%, P = 0.955). LVI was associated with large tumor size (> 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI. CONCLUSION LVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis.

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62–2.27) was demonstrated in USC than in G3EC (P

Objective To develop a nomogram for predicting the probability of 5year survival after definitive concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC). Methods Between 1998 and 2008, 209 patients with LACC were treated with definitive CCRT. Multivariate analysis using Cox proportional hazards regression model was performed. A nomogram based on this Cox model was developed and internally validated by bootstrapping. Its performance was assessed by using the concordance index and a calibration curve. Results The median age was 55years (range, 26–78). Of the patients, 9, 16, 129, 3, 42 and 10 had FIGO stage IB2, IIA, IIB, IIIA, IIIB, and IVA disease, respectively. Histology revealed that 190, 13, 4, and 2 patients had squamous, adenocarcinoma, adenosquamous, and small cell cervical cancer, respectively. In 91 patients, PET/CT was performed before CCRT. The median follow-up period was 51months (range, 6–151) and there were 50 (23.9%) disease-related deaths. Multivariate regression analysis revealed that histology, tumor size, and paraaortic lymph node metastasis (defined by MRI), but not PET/CT before CCRT, were independent predictors of overall survival. A nomogram for predicting the 5year survival incorporating these three significant variables was constructed. The concordance index was 0.69. The predictive ability of the nomogram proved to be superior to that of the FIGO staging system ( p Conclusions The nomogram was a better predictive model for overall survival than the FIGO staging system. If externally validated, it could be used to counsel patients with LACC who must choose additional treatment modalities after definitive CCRT.

Objective To analyse the long-term oncologic outcomes of a fertility-sparing management using oral progestin in young women with endometrial cancer. Methods We analysed 148 patients (age⩽40years) with stage IA, grade 1, endometrioid adenocarcinoma of the uterus who underwent fertility-sparing management using daily oral medroxyprogesterone acetate (MPA) or megestrol acetate (MA). Results 115 (77.7%) showed complete response (CR) to progestin treatment, and 35 (30.4%) of them experienced recurrence after median follow-up time of 66months. The 5-year recurrence-free survival was 68% (95% confidence interval [CI], 58.5–76.9%). However, 33 patients (22.3%) who failed to achieve CR underwent definitive surgical management, and no one had recurrence after median follow-up time of 41months. During progestin treatment and at the time of recurrence, no patient showed clinical progression of disease over stage IA. Body mass index (BMI) ⩾25kg/m 2 was the only significant factor associated with a failure to achieve CR (odds ratio [OR], 3.00; 95% CI, 1.35–6.66; P =0.007). Upon multivariate analysis, BMI⩾25kg/m 2 (OR, 2.14; 95% CI, 1.06–4.31; P =0.033) was significantly associated with a higher risk of recurrence and the use of MPA (compared to MA) (OR, 0.44; 95% CI, 0.22–0.88; P =0.021), maintenance treatment (OR, 0.22; 95% CI, 0.05–0.94; P =0.042) and pregnancy (OR, 0.25; 95% CI, 0.11–0.56; P =0.001) were significantly associated with a lower risk of recurrence. Conclusion Fertility-sparing management was highly effective and safe. BMI 2 , MPA (compared to MA), maintenance treatment and pregnancy were associated with higher possibility of long-term success.

To compare survival and surgical outcomes of laparoscopic (LRH) and open radical hysterectomy (ORH) in patients with stage IB2 and IIA2 cervical cancer.A retrospective analysis was performed on 303 patients with stage IB2 and IIA2 cervical cancer who underwent LRH (n = 115) or ORH (n = 188).Two patients (1.7%) in the LRH group required conversion to laparotomy. There was no difference with respect to operating time, perioperative change in hemoglobin level, and need for transfusion. However, in the LRH group, estimated blood loss (P = 0.003) was significantly lower, time to recovery of bowel movement (P0.001) and length of postoperative hospital stay (P0.001) were significantly shorter, and postoperative complications were significantly less frequent (P = 0.036). The 5-year disease-free survival was 78% in the LRH group and 77% in the ORH group (P = 0.718), and 5-year overall survival was 83% in both groups (P = 0.746). There were no differences in pattern of recurrence (P = 0.225) and median time to recurrence (12 vs. 13 months; P = 0.240).LRH has similar therapeutic efficacy to ORH in patients with bulky early-stage cervical cancer. However, LRH has more favorable surgical outcomes. Therefore, LRH is not only a reasonable alternative to ORH but also the preferred surgical procedure for these patients.

To compare the surgical and oncological outcomes of laparoscopic radical hysterectomy and open radical hysterectomy in obese women with early-stage cervical cancer.The medical records of 166 patients with stage IA2-IIA2 cervical cancer and a body mass index of at least 30 who underwent laparoscopic radical hysterectomy (n=54) or open radical hysterectomy (n=112) at the Asan Medical Center between 1998 and 2011 were reviewed.None of the patients in the laparoscopic radical hysterectomy group required conversion to laparotomy. The resection margin was negative in 98.1% of the laparoscopic radical hysterectomy group and 98.2% of the open radical hysterectomy group (P=.976). No difference between the two groups was observed in terms of operating time, perioperative hemoglobin level change, transfusion requirement, or the number of retrieved lymph nodes. Compared with open radical hysterectomy, laparoscopic radical hysterectomy was associated with a significant reduction in the following: interval to return of bowel movements (2 days compared with 2.7 days, P.001); duration of postoperative hospital stay (9.3 days compared with 21 days, P.001), postoperative complications (5.6% compared with 17.9%, P=.032), and estimated blood loss (494 mL compared with 620 mL, P=.009). After a median follow-up period of 44 months, the 5-year disease-free survival rate was 88% for the laparoscopic radical hysterectomy group and 85% for the open radical hysterectomy group (P=.682). The 5-year overall survival rate was 97% for the laparoscopic radical hysterectomy group and 90% for the open radical hysterectomy group (P=.220).Laparoscopic radical hysterectomy was a preferred alternative to open radical hysterectomy in the present cohort of obese women with early-stage cervical cancer because it is associated with a more favorable surgical outcome without compromising survival outcomes.II.

Introduction The main methods of treatment of endometrial carcinoma are hysterectomy and bilateral oophorectomy with lymphadenectomy. However, another option for hormonal treatment of endometrial carcinoma, the use of progesterone in young patients to preserve childbearing capacity, has been reported, and a high remission rate has been described in well-selected stage I, grade 1 endometrial cancer. Although it is intriguing that hormonal therapy alone can treat endometrial carcinoma without surgery or cytotoxic chemotherapy, the molecular basis for the effects of progesterone on endometrial carcinoma is not clearly known. MicroRNAs (miRNAs) are a class of naturally occurring small, noncoding RNA molecules that control cellular function and are known to function as both tumor suppressors and oncogenes. Thus, in the present study, changes in the miRNA profile of endometrial carcinoma cells on progesterone treatment were studied. Method To elucidate the mechanism of hormonal treatment in endometrial carcinoma cells, we studied the changes in miRNA expression in endometrial carcinoma cells on treatment with progesterone using the Hec1A endometrial carcinoma cell line as a model system. Hec1A cells were treated with medroxyprogesterone acetate, and total RNA was extracted. The changes in the miRNA profile after progesterone treatment were determined using a microarray containing 868 miRNAs. Results Of 868 miRNAs, the expression levels of miR-625*, -21, -142-5p, and 146b-5p were increased by more than 400%, whereas the expression levels of miR-633, -29c, -29*, and -193b were decreased by 50%. To validate the array results, quantitative real-time polymerase chain reactions were performed. Conclusions MiRNA expression was modulated by progesterone treatment in endometrial carcinoma cells, implying a possible critical role of miRNAs in regulating posttranscriptional gene expression on progesterone treatment. Further studies are required to clarify the mechanism involved in the hormonal treatment of endometrial carcinoma.

More than 90% cases of chronic gastrointestinal bleeding can be diagnosed by upper endoscopy and/or colonoscopy, and therefore, obscure gastrointestinal bleeding has been defined as bleeding of unknown origin that persists after these conventional endoscopic evaluation. Gastrointestinal stromal tumors (GISTs) are rare tumors, but the most common form of mesenchymal tumors of the gastrointestinal tract. Small bowel is the second most common primary site for GISTs, and accounts for 2-10% of chronic bleeding sites. GISTs usually present as a sporadic and solitary tumor, and a minority of the cases of multiple GISTs are discovered as forms of hereditary or idiopathic tumor syndromes. Small bowel tumor has been difficult to diagnose because of absence of accurate and proper diagnostic tools. Recently developed wireless capsule endoscopy helps in the diagnostic work-up of small bowel diseases. We report a case of multiple jejunal GISTs presenting melena in a 39-year-old male, which was diagnosed with wireless capsule endoscopy.

Aims and background Radiation therapy provides a safe and effective alternative treatment option for recurrent epithelial ovarian cancer, although it has not been a treatment of choice. We evaluated the efficacy and toxicity of radiation therapy for recurrent epithelial ovarian cancer after chemotherapy according to the disease status. Methods This was a retrospective study of 38 patients with recurrent epithelial ovarian cancer treated with radiation therapy at the Asan Medical Center, Seoul, Korea, between January 1997 and December 2007. We analyzed their clinical characteristics and the outcome of radiation therapy. Results Thirty-eight patients were treated with radiation therapy. Their median age was 51.5 years. Most patients were FIGO stage III (27/38) with serous adenocarcinoma (26/38). All patients had received at least one regimen of platinum-based chemotherapy; 24 patients were sensitive to the first chemotherapy and the others were resistant. Lymph node and abdominopelvic wall were the most common sites of radiation therapy. The response rate was 65.0% (16 complete remissions and 10 partial remissions), and the median regression rate was 78.8% (range, −66.6 to 100.0). Median progression-free survival was 7.2 months (range, 1.0–66.6). In 28 patients who had a solitary relapsed site from the radiographic finding at the time of radiation therapy, it was 10.7 months (range, 1.8–66.6). Neither hematologic nor intestinal toxicity of grade 3–4 was observed. Prognostic factors were sensitivity to platinum and the site treated with radiation therapy. Conclusions Radiation therapy is a treatment that should be considered for recurrent epithelial ovarian cancer, especially in good responders to platinum or patients with solitary relapsed lesions.

Objective To analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary. Methods Patients were divided into those with early-stage (stages I–II, n=93) and advanced-stage (stages III–IV, n=13) GCT and analyzed separately in this retrospective study. Results Of the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival (DFS) rates of groups with and without complete staging were 100% and 84%, respectively (P=0.037). Adjuvant chemotherapy was not significantly associated with DFS (P=0.193). All patients with advanced-stage GCT underwent optimal cytoreduction and received adjuvant chemotherapy with BEP. None of the 6 patients who completed 6 cycles of BEP had recurrence, whereas 5 of the 7 patients (71.4%) who received fewer than 6 cycles of BEP had recurrences and 3 (42.9%) died due to disease. The 5-year DFS rates of these two groups were 100% and 50%, respectively (P=0.022), with cycles of chemotherapy being the only significant factor for DFS in patients with advanced-stage GCT. Conclusions Complete surgical staging is recommended, but lymph node removal is not recommended for early-stage GCT. Optimal debulking followed by six cycles of BEP chemotherapy is recommended for advanced-stage GCT.

Aim The sixth and seventh editions of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system for patients with stage II and stage III colorectal carcinoma (AJCC-6 and AJCC-7) were compared. Method Between 2000 and 2007, 2511 stage II/III colorectal carcinoma patients received primary surgical resection at the Asan Medical Center (Seoul, Korea). All patients were staged using AJCC-6 and AJCC-7 TNM systems. Patients with synchronous or other cancers, those given preoperative chemotherapy or radiotherapy and those in whom fewer than 12 lymph nodes were resected, were excluded. Overall survival (OS) and disease-free survival (DFS) were compared. Results Of 2511 patients, 255 (10.2%) had different stages in the AJCC-6 and AJCC-7. For the AJCC-7, the 5-year OS by stage was 94.2% for stage IIA, 88.8% for stage IIB, 83.5% for stage IIC, 91.8% for stage IIIA, 81.8% for stage IIIB and 72.0% for stage IIIC. The OS and the DFS were not significantly different for the new substages IIB (n = 57) and IIC (n = 34) (P = 0.34 and P = 0.87, respectively). For the 187 patients with stage T3N2a cancer, the OS and the DFS were significantly different from stage IIIB other than T3N2a (P = 0.008 and P = 0.01, respectively) and there were no statistically significant differences in OS between the T3N2a group and the IIIC group (P = 0.46). Conclusion The study indicates that AJCC-7 has better prognostic validity than AJCC-6 for staging of patients with stage II and stage III colorectal carcinoma.