Boron uptake of boronophenylalanine and the effect of boron neutron capture therapy in cervical cancer cells.

There are few studies about boron neutron capture therapy (BNCT) for cervical cancer. The present study evaluated the biodistribution of boronophenylalanine (BPA) and the effect of BNCT on cervical cancer cell lines. BPA exposure and neutron irradiation of cervical cancer cell lines resulted in decreased survival fraction compared to irradiation only. In vivo cervical cancer tumor boron concentration was highest at 2.5 h after BPA intraperitoneal administration, and higher than in the other organs. BNCT may be effective against cervical carcinoma.

Postsurgical urodynamic study of total laparoscopic nerve-sparing radical hysterectomy for uterine cervical cancer.

AIM: To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer. METHODS: This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining. RESULTS: Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections. CONCLUSION: We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Endometrial Cancer Patient-Derived Xenograft Models: A Systematic Review.

BACKGROUND: Because patient-derived xenograft (PDX) models resemble the original tumors, they can be used as platforms to find target agents for precision medicine and to study characteristics of tumor biology such as clonal evolution and microenvironment interactions. The aim of this review was to identify articles on endometrial cancer PDXs (EC-PDXs) and verify the methodology and outcomes. METHODS: We used PubMed to research and identify articles on EC-PDX. The data were analyzed descriptively. RESULTS: Post literature review, eight studies were selected for the systematic review. Eighty-five EC-PDXs were established from 173 patients with EC, with a total success rate of 49.1%. A 1-10 mm3 fragment was usually implanted. Fresh-fragment implantation had higher success rates than using overnight-stored or frozen fragments. Primary tumors were successfully established with subcutaneous implantation, but metastasis rarely occurred; orthotopic implantation via minced tumor cell injection was better for metastatic models. The success rate did not correspond to immunodeficiency grades, and PDXs using nude mice reduced costs. The tumor growth period ranged from 2 weeks to 13 months. Similar characteristics were observed between primary tumors and PDXs, including pathological findings, gene mutations, and gene expression. CONCLUSION: EC-PDXs are promising tools for translational research because they closely resemble the features of tumors in patients and retain molecular and histological features of the disease.

Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review.

BACKGROUND: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. METHODS: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. RESULTS: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1-3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. CONCLUSION: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1-3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.

Uterine leiomyoma in a 13-year-old adolescent successfully treated with laparoscopic myomectomy: A case report.

RATIONALE: Uterine leiomyoma, which is very common gynecological tumor in the reproductive years, is extremely rare in adolescence. We herein report a case of a uterine leiomyoma treated with laparoscopic surgery in an adolescent. PATIENT CONCERNS: A 13-year-old girl with no gravida and her first menses at 11 years of age reported feeling bloated. She had a regular menstrual cycle but felt increased abdominal distension. DIAGNOSIS: Transabdominal ultrasound and magnetic resonance imaging revealed uterine leiomyoma with a diameter of 10 cm. INTERVENTION: Laparoscopic myomectomy was performed. OUTCOMES: The total weight of the leiomyoma removed was 660 g with pathological diagnosis of uterine leiomyoma. The postoperative course was uneventful. The patient was free of disease at the follow-up consultation 18 months after the treatment. LESSONS: Laparoscopic approach is a very useful and minimally invasive surgery for symptomatic leiomyoma in adolescents.

Urodynamic outcomes after pelvic nerve-sparing radical hysterectomy with or without neoadjuvant chemotherapy.

OBJECTIVE: Our purposes of this study were to characterize a group of bulky cervical cancer patients who underwent a nerve sparing radical hysterectomy (NSRH) with or without neoadjuvant chemotherapy (NAC), to compare surgical outcomes and the preservation of bladder function, and to compare prognoses. RESULTS: Fifty-three patients had NSRH without NAC (Group A), and 33 patients had NSRH after NAC (Group B). With regard to prognostic factors, there was only a significant difference between both groups with regard to lymph node metastasis (15% vs 42%, P = 0.01). Moreover, bladder function in Group B patients improved to the same extent as the preoperative rate three months postoperatively. These data were similar to the results in Group A. With regard to overall survival, the 5-year survival rate was 98.1% (95% confidence interval (CI) 87.8-99.7) in Group A and 86.7% (95% CI 71.7-96.7) in Group B (P > 0.1). METHODS: We retrospectively identified 86 patients with cervical cancer who underwent NSRH at Osaka Medical College from May 2009 to November 2016. NAC was performed via balloon occluded arterial infusion. We extracted data on the patient's stage of progress, tumor volume, histological subtype, bleeding volume, urodynamic study results, and postoperative complications. The data were divided into two groups - those patients who received NAC and those who did not - and then compared. CONCLUSIONS: According to our analysis, NSRH surgery after NAC via balloon occluded arterial infusion brings beneficial results to patients with bulky IB2 to IIB cervical cancers.

Intraperitoneal cytology after laparoscopic radical hysterectomy with vaginal closure without the use of a manipulator for cervical cancer: a retrospective observational study.

PURPOSE: Although laparoscopic radical hysterectomy (LRH) has been performed for patients with cervical cancer because of its minimal invasiveness, a recent large prospective study showed that LRH was associated with a lower rate of disease-free survival and overall survival. However, the reason for these results is not apparent. The aim of this study was to evaluate the tumor spillage during LRH with vaginal closure without the use of a manipulator. PATIENTS AND METHODS: Twenty-four patients with cervical cancer underwent total LRH with vaginal closure. To evaluate the leakage of cancer cells during surgery, peritoneal cytology was performed before and after hysterectomy. RESULTS: Among 24 patients with cervical cancer, 2 had stage IA2 disease, 19 had stage IB1 disease and 3 had stage IIA1 disease. Two patients had lymph node metastasis. The median tumor size on final pathology was 9 mm. No cancer cells were identified before or after hysterectomy in any patients. CONCLUSION: Total LRH with vaginal closure did not increase the propensity for tumor spillage in the peritoneal cavity.

Preoperative diffusion-weighted magnetic resonance imaging and intraoperative frozen sections for predicting the tumor grade in endometrioid endometrial cancer.

OBJECTIVE: The histological tumor grade is a strong predictor of nodal metastasis in endometrial cancer; as such, an accurate pre- or intraoperative diagnosis is important for performing lymphadenectomy. METHODS: Ninety-one patients with endometrioid endometrial cancer were imaged on DW-MRI with the apparent diffusion coefficient (ADC) calculated and a frozen section (FS) diagnosis made before and at hysterectomy. The diagnostic accuracy for predicting the tumor grade for diffusion weighted magnetic resonance inaging (DW-MRI) and the FS diagnosis compared to the ultimate histologic status was analyzed. RESULTS: Among 91 patients with endometrioid endometrial cancer, high-grade (endometrioid G3) tumors had lower ADC values than low-grade (endometrioid G1/2) tumors. The cut-off of the mean ADCmean values for predicting high-grade tumors resulted in 743×10-6 mm2/sec according to the receiver operating characteristic curve. The true positive rates of ADC values and FSs for the prediction of high-grade tumors did not differ to a statistically significant extent (73.3% vs. 66.7%, p=0.7), however, the true negative rate of ADC values for the prediction of low-grade tumors was significantly lower than that of the FSs (64.5% vs. 98.7%, p=0.01). The kappa statistics of ADC values and FSs were 0.23 and 0.73, respectively. Of note, all five patients with high-grade tumors for whom intraoperative FSs indicated low-grade tumors were predicted to have high-grade tumors on preoperative DW-MRI. CONCLUSION: A FS diagnosis is more suitable for predicting high-grade tumors than DW-MRI; however, physicians should pay close attention to tumors with low ADC values on preoperative DW-MRI.

A case of ovarian clear cell carcinoma arising from ovarian mature cystic teratoma.

BACKGROUND: It is well known that ovarian mature cystic teratomas (MCTs) occasionally go through malignant transformations. Among these, approximately 75% of histological types are squamous cell carcinoma, with the other types being exceptionally rare. We report an extremely rare case of ovarian clear cell carcinoma arising from ovarian mature cystic teratoma. CASE PRESENTATION: The case was a 71-year-old woman with abdominal distention. Ultrasonography and magnetic resonance imaging showed a huge mass in her abdominal cavity. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG uptake not only in the pelvic tumor but also in the hepatic nodule, thus suggesting metastases. We performed a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and an omentectomy. The pathological diagnosis showed clear cell carcinoma of the right ovary which arose from the MCT with malignant transformation pT2aNXM1. Although the patient underwent chemotherapy, she died after 17 months. CONCLUSION: This case is histologically characteristic of the proof of transition from simple squamous epithelium via simple glandular epithelium to papillary change with atypia. This is the first case report of unaccompanied clear cell carcinoma arising from MCT reported in English literatures.

Neoadjuvant intra-arterial chemotherapy using an original four-lumen double-balloon catheter for locally advanced uterine cervical cancer.

OBJECTIVE: We report a balloon-occluded arterial infusion therapy with an original four-lumen double-balloon catheter (4L-DB) which allows for the efficient injection of an anticancer agent at a high concentration to the target spot for patients with locally advanced uterine cervical cancer. METHODS: One hundred and forty-three patients with locally advanced cervical cancer treated with neoadjuvant intra-arterial chemotherapy (NAIAC) or a primary radical hysterectomy (PRH) were retrospectively assessed. The patients in the NAIAC group received irinotecan 70 mg/m2 intravenously on day 1 and 8 and cisplatin 70 mg/m2 intra-arterially using the 4L-DB on day 2 of a 21-day course, and two courses were performed in principle. The radical hysterectomy was performed within 6 weeks after NAIAC. RESULTS: Ninety-four patients were treated with NAIAC, and 49 patients undertook a PRH. The response rate of NAIAC on MRI was 92.6%. Fourteen patients (14.6%) had no evidence of cancer cells on pathologic diagnoses. The NAIAC group had a longer disease-free survival than the PRH group (p=0.02); however, the overall survival was not significantly different. The relative risk (RR) for recurrence was higher in patients with lymph node metastasis (RR, 4.31; 95% CI, 2.23-8.43) and lower in those who underwent NAIAC (RR, 0.30; 95% CI, 0.14-0.68). CONCLUSION: Our results with NAIAC using the 4L-DB catheter in locally advanced cervical cancer indicates beneficial effects on primary lesions and improves disease-free survival.

The detection of sentinel lymph nodes in laparoscopic surgery can eliminate systemic lymphadenectomy for patients with early stage endometrial cancer.

BACKGROUND: The examination of a sentinel lymph node (SLN), where lymph node metastasis first occurs, may be advocated as an alternative staging technique. The aim of this study was to evaluate the feasibility and detection rates of an SLN biopsy in patients with endometrial cancer. STUDY DESIGN: Two hundred and eleven patients with endometrial cancer underwent an SLN biopsy at hysterectomy using three kinds of tracers including 99m-technetium-labeled tin colloid (99mTc), indigo carmine and indocyanine green. Factors related to the side-specific detection rate, sensitivity and false negative rate were analyzed. RESULTS: The detection rates of the SLN biopsy using 99mTc, indigo carmine and indocyanine green were 77.9, 17.0 and 73.4%, respectively. The detection rate was lower in elderly patients (≥60 years) (67.9 vs 89.2%, p < 0.01), patients with >50% myometrial invasion (68.3 vs 85.2%, p < 0.01), patients with high-grade tumors (69.5 vs 84.9%, p < 0.01) and patients who underwent laparotomy (71.2 vs 84.9%, p < 0.01). There were no significant differences in body mass index. The sensitivity was not significantly different in any factor. However, the false negative rate was higher in patients with > 50% myometrial invasion (11.5 vs 1.2%, p < 0.01), high-grade tumors (13.3 vs 0.8%, p < 0.01) and who underwent laparotomy (12.2 vs 0.4%, p < 0.01). CONCLUSION: Patients who underwent laparoscopy with < 50% myometrial invasion and low-grade tumors not only have higher detection rates, but also have lower false negative rates. These patients may avoid systemic lymphadenectomy according to the status of the SLN biopsy.

The efficacy of the cyclin-dependent kinase 4/6 inhibitor in endometrial cancer.

BACKGROUND: PD-0332991, the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, causes cell cycle arrest by inhibiting phosphorylation of retinoblastoma (Rb) protein. The aim of this study was to evaluate the therapeutic potential of PD-0332991 in endometrial cancer. METHODS AND FINDINGS: Four human endometrial cancer cell lines, ECC, HEC1A, HEC108 and TEN, were treated with PD-0332991 and their function was evaluated. In vivo, the therapeutic efficacy was evaluated in a model of subcutaneous endometrial cancer. An immunohistochemical analysis was performed in 337 endometrial cancer specimens. A proliferation assay revealed that 2 of the 4 cell lines that expressed Rb were sensitive to PD-0332991 with an IC50 of 0.65 µM (HEC1A) and 0.58 µM (HEC108), respectively. Both cell lines had G0/G1 cell cycle arrest after treatment with PD-0332991 according to flow cytometry. In vivo, PD-0332991 had antitumoral efficacy with a reduction in the activity of Ki67 and phosphorylation of Rb. Immunohistochemical analyses revealed that the positive rate of Rb was 67.7%, however, there was no significant relationship between the expression levels of Rb and the tumor grade. CONCLUSIONS: PD-0332991 had therapeutic potential against endometrial cancer cell lines expressing Rb protein. Our immunohistochemical analysis revealed that approximately 70% of patients with endometrial cancer might have therapeutic indications for PD-0332991. Of note, the tumor grade had no impact on the indications for treatment.

CD24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways.

The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary ovarian carcinoma tissues, which were obtained from 174 patients, and that the expression of CD24 was an independent predictor of survival in patients with ovarian cancer. The expression of CD24 has been found to be correlated with the FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the EMT phenomenon, which is involved in cell invasion, the highly proliferative phenotype, colony formation and which is associated with cisplatin resistance and the properties of CSCs, via the activation of PI3K/Akt, NF-κB and ERK in Caov-3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been shown to have a greater potential for intra-abdominal tumor cell dissemination in in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in ovarian cancer, and that CD24 amplified cell growth-related intracellular signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal pathways. We believe that CD24 is a key molecule of metastatic progression in the EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.

The detection of sentinel lymph nodes in laparoscopic surgery for uterine cervical cancer using 99m-technetium-tin colloid, indocyanine green, and blue dye.

OBJECTIVE: Our objective was to determine the feasibility and detection rates and clarify the most effective combination of injected tracer types for sentinel lymph node (SLN) mapping in uterine cervical cancer in patients who have undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). METHODS: A total of 119 patients with cervical cancer underwent SLN biopsy at radical hysterectomy using three types of tracers. The various factors related to side-specific detection rate, sensitivity, and false negative (FN) rate were analyzed. RESULTS: The SLN detection rates using 99m-technetium ((99m)Tc)-tin colloid, indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%, respectively. The patients with ≥2-cm-diameter tumors and those who received NAC had lower detection rates than those with <2-cm-diameter tumors (75.7% vs. 91.5%, p<0.01) and those who did not receive NAC (67.9% vs. 86.3%, p<0.01), respectively. Laparoscopic procedures had a higher detection rate than laparotomy (100.0% vs. 77.1%, p<0.01). No factors significantly affected the sensitivity; however, the patients with ≥2-cm-diameter tumors (86.0% vs. 1.4%, p<0.01), NAC (19.4% vs. 2.2%, p<0.01), and those who underwent laparotomy (7.4% vs. 0%, p<0.01) had an unfavorable FN rate. CONCLUSION: Among the examined tracers, (99m)Tc had the highest detection of SLN mapping in patients with uterine cervical cancer. Patients with local advanced cervical cancer with/without NAC treatment might be unsuited for SLN mapping. SLN mapping is feasible and results in an excellent detection rate in patients with <2-cm-diameter cervical cancer. Laparoscopic surgery is the best procedure for SLN detection in patients with early-stage disease.

CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer.

CD24, a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol-anchored cell surface protein, plays an important role in the carcinogenesis of various human malignancies. However, its function in cervical cancer remains unclear. The aim of the present study was to evaluate the expression of CD24 clinicopathologically and to analyze its functional behavior biologically in cervical cancer. A total of 117 uterine cervical cancer tumors were immunohistochemically analyzed using a CD24 monoclonal antibody on paraffin blocks. We also examined whether CD24 enhanced the invasive activity or the Akt, ERK, NF-κB and MMP activity in a uterine cervical cancer cell line (CaSki) by a western blot analysis. The patients with enhanced CD24 expression had a higher rate of advanced clinical stage (50 vs. 16.5%, p<0.01), lymph node metastasis (34.6 vs. 14.3%) and lymphovascular involvement (65.4 vs. 20.4%, p=0.01), and a poor overall and disease-free survival (5-year survival rate: 62 vs. 86%, p=0.03). CD24 overexpression in CaSki cells resulted in activation of Cell Signaling proteins, including Akt, ERK, NF-κB and MMP-9. An invasion assay showed that CD24 overexpression in CaSki cells led to increased invasion ability. The CD24 overexpression also increased mRNA expression of Slug but not Snail. Moreover, the CD24 overexpression also decreased expression of E-cadherin and increased N-cadherin protein levels. Increased expression of CD24 may be associated with tumor progression and prognosis in patients with uterine cervical cancer. CD24 expression may therefore be used not only as a prognostic marker in uterine cervical cancer, but also as a target for the development of new therapeutic approaches.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer.

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Preoperative MRI and intraoperative frozen section diagnosis of myometrial invasion in patients with endometrial cancer.

OBJECTIVE: The rate of lymph node metastasis is extremely low in patients with low-risk endometrial cancer; lymphadenectomy may be unnecessary for these patients under an accurate preoperative diagnosis. The aim of this study was to evaluate the diagnostic accuracy of myometrial invasion (MI) on preoperative magnetic resonance imaging (MRI) and intraoperative frozen sections (FSs). MATERIALS AND METHODS: Endometrial cancer was diagnosed in a total of 378 patients by preoperative endometrial curettage, preoperative magnetic resonance imaging MRI, and intraoperative FSs; the 378 patients underwent hysterectomy. The depth of MI was evaluated between the preoperative MRI, intraoperative FSs, and final paraffin sections (PSs). The histologic grade was also evaluated between preoperative endometrial curettage, intraoperative FSs, and final PSs. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value for deep MI (≥ 50%) on MRI were 57.8%, 92.0%, 69.3%, and 87.5%, respectively, with a kappa value of 0.53. These figures on FSs were 66.7%, 97.9%, 90.9%, and 90.4%, with a kappa value of 0.71. When grade 3 endometrioid adenocarcinoma, serous carcinoma, clear cell carcinoma, and carcinosarcoma were considered high-grade tumors, the grade evaluation at the time of FSs was 70.2%, 99.0%, 96.1%, and 89.7%, with a kappa value of 0.75. In the patients with low-grade tumors, including grade 1 or 2 endometrioid adenocarcinoma on preoperative endometrial curettage, the rate of unexpected lymph node metastasis did not differ significantly between the patients who had a diagnosis of MI and lymph node metastasis by MRI and those with diagnosis of MI and histological grade by FSs (4.0% vs 2.6%; P > 0.05). CONCLUSIONS: Frozen sections had a higher agreement rate for MI than MRI; however, MRI is still considered an acceptable modality to guide preoperative decisions regarding lymphadenectomy especially in grade 1 or 2 endometrioid adenocarcinoma.

Genitofemoral neuropathy after pelvic lymphadenectomy in patients with uterine corpus cancer.

OBJECTIVE: The aim of this study was to estimate the incidence, etiology, and outcomes of genitofemoral neuropathy after pelvic lymphadenectomy (PLD) for uterine corpus cancer. MATERIALS AND METHODS: The medical records of women who underwent PLD for uterine corpus cancer between June 2001 and June 2013 were reviewed. Information regarding neuropathy was directly reported by each subject. RESULTS: Thirty-two of 300 patients undergoing PLD during the defined period experienced postoperative neuropathy due to genitofemoral nerve injury, for an incidence of 10.7%. The patients treated with PLD with para-aortic lymphadenectomy (PALD) exhibited a lower rate of genitofemoral neuropathy than those treated without PALD (4.3% vs 13.5%, P = 0.01). The laparoscopy group displayed a higher rate of genitofemoral neuropathy than the laparotomy group (19.1% vs 9.1%, P = 0.04). A total of 81.3% of the patients experienced a full recovery, with a medium time to resolution of 6 months (3-12 months). The administration of adjuvant chemotherapy, including paclitaxel, did not extend the time to recovery. CONCLUSIONS: Neuropathy resulting from genitofemoral nerve injury is not infrequent; however, most of the patients recover completely. In this study, the use of laparoscopic procedures increased the incidence of genitofemoral neuropathy, whereas that of PALD did not.

The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer.

OBJECTIVES: The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of the E-cadherin expression, which is primarily controlled by Snail-related zinc-finger transcription factors. The aim of this study was to evaluate the prognostic impact of the expression of EMT-related proteins (E-cadherin and Snail) in patients with ovarian cancer. METHODS: An immunohistochemical analysis was conducted using tissue microarray samples of 174 primary tumors and 34 metastases of ovarian carcinoma, and the relationships between the protein expression, clinicopathological features and outcomes were investigated. RESULTS: A reduced E-cadherin expression was observed in 36.8% of the primary tumors and 30.4%, 35.7%, 37.7% and 52.7% of the stage I, II, III and IV tumors, respectively. The nuclear expression of Snail was positive in 33.9% of the primary tumors. The rate of an EMT-positive status, as represented by both a reduced E-cadherin expression and a nuclear expression of Snail, was significantly higher in the patients with peritoneal dissemination than in those without (p < 0.05). The EMT status was significantly associated with both the progression-free survival and overall survival (p <0.01). A multivariate analysis showed an EMT-positive status to be a significant predictor of both the progression-free survival (p < 0.05) and overall survival (P < 0.01). CONCLUSIONS: These data indicate that the EMT status is significantly associated with peritoneal metastasis and both the progression-free survival and overall survival in patients with ovarian cancer. Therefore, clarifying and controlling EMT signaling is a promising approach to molecular targeted therapy for ovarian cancer.

Gemcitabine as a molecular targeting agent that blocks the Akt cascade in platinum-resistant ovarian cancer.

BACKGROUND: Gemcitabine (2', 2' -difluorodeoxycytidine) is one of many nonplatinum drugs that exhibit activity in recurrent, platinum-resistant ovarian cancer. However, the molecular mechanisms by which Gemcitabine treatment inhibits the proliferation of platinum-resistant ovarian cancer cells still remain unclear. We investigated whether Gemcitabine increases the efficacy of Cisplatin in platinum-resistant ovarian cancer models in vitro and in vivo. METHODS: We used Cisplatin-resistant Caov-3 cells, A2780CP cells and Cisplatin-sensitive A2780 cells to examine the sensitivity of the cell viability of Cisplatin and Gemcitabine using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and the sensitivity of the invasive activity of Cisplatin and Gemcitabine using an invasion assay with Matrigel. We examined the Akt kinase activity and matrix metalloproteinase 9 (MMP9) expression following Cisplatin and Gemcitabine treatment using a Western blot analysis and the mRNA expression of vascular endothelial growth factor (VEGF) using semi-quantitative RT-PCR. Moreover, we evaluated the effects of Cisplatin and Gemcitabine on the intra-abdominal dissemination of ovarian cancer in vivo. RESULTS: Gemcitabine significantly inhibited Cisplatin-induced Akt activation in the Caov-3 and A2780CP cells, but not in the A2780 cells. In the presence of Gemcitabine, Cisplatin-induced growth inhibition and apoptosis were significantly enhanced in the Caov-3 and A2780CP cells. Co-treatment with Cisplatin and Gemcitabine almost completely inhibited invasion of both types of cells through the Matrigel; however, neither Cisplatin nor Gemcitabine alone inhibited the invasion of both types of cells. Gemcitabine inhibited not only the Cisplatin-induced activation of Akt, but also the MMP9 and mRNA expression of VEGF. Moreover, treatment with Gemcitabine increased the efficacy of Cisplatin-induced growth inhibition of the intra-abdominal dissemination and production of ascites in the athymic nude mice inoculated with Caov-3 cells. CONCLUSIONS: We herein demonstrated that Gemcitabine inhibits the Akt kinase activity and angiogenetic activity following treatment with Cisplatin in platinum-resistant ovarian cancer cells. These results provide a rationale for using Gemcitabine in clinical regimens containing molecular targeting agents against platinum-resistant ovarian cancers.