A lower ratio of reduced to total albumin in serum is associated with protein nutritional status of pregnant women in Japan.

Protein-energy undernutrition is potentially prevalent among Japanese pregnant women, and biomarkers that objectively indicate the protein nutritional status during pregnancy may help in implementing appropriate protein supplementation to these women. We hypothesized that a serum parameter of pregnant women, the ratio of reduced to total albumin (reduced ALB ratio), would be associated with protein intake during pregnancy. The serum reduced ALB ratio of pregnant women was compared with protein intake and with gestation outcomes (gestation length and infant birth weight) in an observational study of 115 Japanese pregnant women. The serum reduced ALB ratio in the third trimester tended to be positively correlated with gestation length (P = .07). Infant birth weights tended to be different between protein intake tertiles (P = .09); the mean infant birth weight was higher in the third tertile compared with the first and second tertiles. The protein intake of pregnant women was significantly and positively correlated with the serum reduced ALB ratio in the second trimester. The serum reduced ALB ratio reflects protein nutritional status during pregnancy and may contribute to healthier gestation outcomes.

Association between Edinburgh Postnatal Depression Scale and Serum Levels of Ketone Bodies and Vitamin D, Thyroid Function, and Iron Metabolism.

Suicide due to postpartum depression is the most common perinatal-related death and is a social concern in Japan. Nutritional deficiencies during pregnancy may contribute to postpartum depression; therefore, we investigated the relationship between postpartum depression and nutritional status during pregnancy and postpartum. We focused specifically on ketone bodies because they are known to protect brain cells. The relationship between the Edinburgh Postnatal Depression Scale (EPDS) scores and the serum levels of ketone bodies and vitamin D, thyroid function, and iron metabolism was examined. Overall, 126 pregnant women were identified for the study, and 99 were eventually included in the analysis. We defined an EPDS score of ≥9 as being positive for postpartum depression, and serum ketone levels were found to be higher in the group with an EPDS score of ≥9 during the second trimester; however, there were no other significant findings. We may be able to predict postpartum depression from a pregnant woman's serum ketone levels in the second trimester. There was a positive correlation between the EPDS scores at 3 days and 1 month postpartum (r = 0.534, p < 0.001). EPDS scores assessed in the early postpartum period may be useful for the timely detection of postpartum depression.

Evaluation of Clinical Practice Guidelines for Rare Diseases in Japan.

Introduction: The insufficient quantity and quality of clinical epidemiological evidence in the field of rare diseases have posed methodological challenges to develop clinical practice guidelines (CPGs). Guideline development groups struggle to provide patients and their families with beneficial guidance, such as that for medical care and in complex circumstances. Motivated by the challenges, we focused on information on resources for supporting the daily and social life to improve the CPGs for users. We aimed to assess the methodological quality of CPGs for rare diseases in Japan and to evaluate information on resources to support the daily and social life in the CPGs. Methods: We conducted a systematic search using PubMed, three electronic Japanese databases, and two hand-searched sources in Japan. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument with six domains was used to assess the methodological quality of the CPGs. A content analysis of the CPG text was conducted using five keywords as information on non-medical resources, e.g., "Intractable Disease Consultation Support Center," "Japan Intractable Disease Information Center," and "Patient Association." Results: A total of 55 CPGs met the inclusion criteria. Among four domains of AGREE II with low scores (Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence), Rigor of Development had the lowest median score. As for information on non-medical resources, 41 CPGs included at least 1 of the 5 keywords, while 14 CPGs included none. Conclusions: At the Rigor of Development domain, methodological challenges may have resulted in an insufficient description of items regarding the translation evidence to recommendations. As the sufficiency of five keywords as information on non-medical resources could be improved, the information will be advocative as clues to provide pragmatic guidance, particularly for rare diseases with limited medical evidence.

The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys.

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders.

Investigation of clinicopathological features of vulvar cancer in 1068 patients: A Japanese Gynecologic Oncology Group (JGOG) nationwide survey study.

OBJECTIVE: Vulvar cancer is a rare malignancy in the aging population, and optimizing treatment strategies requires large-scale investigation of the clinicopathological features of this disease. In Japan, no such surveys have been conducted in the past 30 years. This large-scale retrospective multi-center study aimed to examine the clinicopathological features of vulvar cancer in Japan. METHODS: Upon obtaining ethical approval by the participating institutions' review boards, the medical records of patients with vulvar cancer, who were treated between 2001 and 2010 were reviewed. The impact of clinicopathological factors on overall survival (OS) was investigated using a multivariate Cox regression model. RESULTS: After applying the inclusion and exclusion criteria, 1068 patients treated in 108 centers were included. The median age was 72 years. The disease was in stage I in 402 patients (37.6%), stage II in 249 patients (23.3%), stage III in 252 patients (23.6%), and stage IV in 165 patients (15.4%). Squamous cell carcinoma, Paget's disease, adenocarcinoma, and other diseases were diagnosed in 773 (72.4%), 154 (14.4%), 59 (5.5%), and 82 (7.7%) patients, respectively. Positive inguino-femoral lymph nodes were found in 265 (24.8%) patients. The 5-year OS rate for stage I, II, III, and IV vulvar cancer were 85.6%, 75.1%, 48.8%, and 40.0%, respectively. CONCLUSION: Our study shows that advanced age, disease stage, histological diagnosis, tumor diameter, and lymph node metastases significantly affect the OS of patients with vulvar cancer in Japan.

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis.

BACKGROUND: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. METHODS: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). RESULTS: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were - 0.43 (95% CI: - 0.77 to - 0.09) days for the time to first postoperative flatus, - 0.29 (95% CI: - 0.59 to 0.01) days for the time to first postoperative BM, and - 0.95 (95% CI: - 1.70 to - 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35-1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. CONCLUSION: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

A Multicenter Prospective Survey of Adverse Events Associated with Acupuncture and Moxibustion in Japan.

Background: There have been only a few prospective surveys on adverse events (AEs) in Japanese-style acupuncture practice, and these surveys were conducted only in a single college acupuncture clinic. Objective: The goal of this research was to assess the safety of acupuncture and moxibustion performed in educational facilities in Japan. Materials and Methods: This was a multicenter prospective survey, using paper reporting forms. It was conducted in eight acupuncture clinics affiliated with educational institutions. The subjects were outpatients attending the clinics. The main outcome measure was the number of reported adverse events. The study was conducted for 5-7 months at each facility between October 2014 and June 2015. Participating acupuncture practitioners were instructed to self-report AEs observed during and after treatment; patients were interviewed upon treatment completion. For returning patients, treatment was preceded by an interview survey regarding the AEs identified after the previous treatment session. A specialized 4-sheet questionnaire was used. Results: Two hundred and thirty-two acupuncture practitioners participated, 2180 patients received treatment, and there were 14,039 sessions, overall. In total, 847 (6.03%) AEs were reported. The most common AEs included subcutaneous bleeding and hematomas (370, 2.64%), followed by discomfort (109, 0.78%) and residual pain at insertion points (94, 0.67%). No infections or serious AEs were reported. Conclusions: Acupuncture and moxibustion performed in educational facilities in Japan were safe because most of the AEs reported were mild and transient. However, the risk cannot be defined definitely because the survey sample size was too small.

Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression.

Overexpression of IQGAP1 and microRNA (miRNA) dysregulation are frequent in human tumors, but little is known about the role of IQGAP1 and its relationship to miRNA in endometrial carcinogenesis. We demonstrate that IQGAP1 activates the epithelial-mesenchymal transition (EMT) program and that miR-124 directly represses IQGAP1 expression in endometrial cancer (EC) cells. The overexpression of IQGAP1 stimulates EMT features and enhances migration, invasion and proliferation of EC cells, whereas knocking down IQGAP1 expression reverses EMT and inhibits these malignant properties. Using miRNA microarray profiling, we identified 29 miRNAs (let-7b, let-7f, miR-10b, miR-15b, miR-23a, miR-24, miR-25, miR-27a, miR-29b, miR-30a-5p, miR-34a, miR-124, miR-127, miR-130b, miR-148a, miR-155, miR-191*, miR-194, miR-224, miR-362, miR-409-3p, miR-422b, miR-424, miR-453, miR-497, miR-518d, miR-518f*, miR-526a and miR-656) that are significantly down-regulated in an in vitro-selected highly invasive derivative cell line (HEC-50-HI) relative to the parental HEC-50 cells. We further identified miR-124 as a direct regulator of IQGAP1 in EC cells. Enforced expression of miR-124 suppresses EC cell invasion and proliferation. The expression of IQGAP1 mRNA was significantly elevated in EC tissues, while the expression of miR-124 was decreased. The downregulation of miR-124 correlates with a poor survival outcome for patients with EC. Treating EC cells with the demethylating agent 5-aza-2'-deoxycytidine increased miR-124 expression and down-regulated IQGAP1 levels. Our data suggest that IQGAP1 promotes EMT, migration and invasion of EC cells. MiR-124, a novel tumor suppressor miRNA that is epigenetically silenced in EC, can reverse EMT and the invasive properties, by attenuating the expression of the IQGAP1 oncogene.

Reactivating p53 functions by suppressing its novel inhibitor iASPP: a potential therapeutic opportunity in p53 wild-type tumors.

Although mutational inactivation of p53 is found in 50% of all human tumors, a subset of tumors display defective p53 function, but retain wild-type (WT) p53. Here, direct and indirect mechanisms leading to the loss of WT p53 activities are discussed. We summarize the oncogenic roles of iASPP, an inhibitor of WT p53, in promoting proliferation, invasion, drug or radiation-resistance and metastasis. From the therapeutic view, we highlight promising perspectives of microRNA-124, peptide and small molecules that reduce or block iASPP for the treatment of cancer. High iASPP expression enhances proliferation, aggressive behavior, the resistance to radiation/chemotherapy and correlates with poor prognosis in a range of human tumors. Overexpression of iASPP accelerates tumorigenesis and invasion through p53-dependent and p53-independent mechanisms. MicroRNA-124 directly targets iASPP and represses the growth and invasiveness of cancer cells. The disruption of iASPP-p53 interaction by a p53-derived peptide A34 restores p53 function in cancer cells. The inhibition of iASPP phosphorylation with small molecules induces p53-dependent apoptosis and growth suppression. The mechanisms underlying aberrant expression of iASPP in human tumors should be further investigated. Reactivating WT p53 functions by targeting its novel inhibitor iASPP holds promise for potential therapeutic interventions in the treatment of WT p53-containing tumors.

Lymphovascular Space Invasion Portends Poor Prognosis in Low-Risk Endometrial Cancer.

OBJECTIVE: The prognostic significance of lymphovascular space invasion (LVSI) in patients with early-stage endometrial cancer is not established. We sought to determine if LVSI status in patients with early-stage low-risk endometrial cancer correlates with recurrence and survival. METHODS: The records of all women who underwent hysterectomy for primary treatment of endometrial cancer from January 2006 through January 2011 at 1 academic institution were reviewed. Patients with grade 1 or 2 endometrioid histology, myometrial invasion less than 50%, and disease confined to the uterus (clinical International Federation of Obstetrics and Gynecology stage IA) were analyzed. Fisher exact test and the Wilcoxon rank-sum test were applied to compare patients with and without LVSI. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Two hundred forty patients met the inclusion criteria. Forty (16.7%) had LVSI. Ninety-one patients (37.9%) underwent lymphadenectomy. Median tumor size was 30 mm in patients with and 26 mm in patients without LVSI (P = 0.150). Thirty patients (12.5%) received adjuvant therapy. Site of recurrence did not differ between patients with and without LVSI. Patients with LVSI were more likely to have myometrial invasion (P < 0.001), postoperative pathologic grade 2 disease (P < 0.001), to undergo lymphadenectomy (P = 0.049) and receive adjuvant therapy (P < 0.001). The 5-year cumulative incidence of recurrence was 3.8% in the no-LVSI group and 14.2% in the LVSI group (P = 0.053). The presence of LVSI was significantly associated with worse RFS (P = 0.002) and OS (P = 0.013). CONCLUSIONS: Patients with low-risk endometrial cancer and LVSI have worse RFS and OS despite being more likely to undergo lymphadenectomy and adjuvant therapy.

Human papillomavirus type 16 sequence variation in concurrent vulvar and penile carcinoma in a married couple.

We encountered an elderly married couple with concurrent vulvar and penile carcinoma with an Asian variant of human papillomavirus type 16. Asian variants might have an elevated risk of concurrent external genital carcinomas of a male and a female, and analysis of human papillomavirus variants might be important to understand the mechanism of carcinogenesis.

MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.

MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/FOS axis is a potential therapeutic target for endometrial cancer.

The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer.

Activation of the PI3K/AKT pathway, a common mechanism in all subtypes of endometrial cancers (endometrioid and non-endometrioid tumors), has important roles in contributing to epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features. MicroRNAs (miRNAs) are small non-coding RNA molecules that concurrently affect multiple target genes, and regulate a wide range of genes involved in modulating EMT and CSC properties. Here we overview the recent advances revealing the impact of miRNAs on EMT and CSC phenotypes in tumors including endometrial cancer via regulating PI3K/AKT pathway. MiRNAs are crucial mediators of EMT and CSC through targeting PTEN-PI3K-AKT-mTOR axis. In endometrial cancer cells, miRNAs can activate or attenuate EMT and CSC by targeting PTEN and other EMT-associated genes, such as Twist1, ZEB1 and BMI-1. More detailed studies of miRNAs will deepen our understanding of the molecular basis underlying PI3K/AKT-induced endometrial cancer initiation and progression. Targeting key signaling components of PI3K/AKT pathway by restoring or inhibiting miRNA function holds promise as a potential therapeutic approach to suppress EMT and CSC in endometrial cancer.

Lymphadenectomy can be omitted for low-risk endometrial cancer based on preoperative assessments.

OBJECTIVE: According to the International Federation of Gynecology and Obstetrics staging, some surgeons perform lymphadenectomy in all patients with early stage endometrial cancer to enable the accurate staging. However, there are some risks to lymphadenectomy such as lower limb lymphedema. The aim of this study was to investigate whether preoperative assessment is useful to select the patients in whom lymphadenectomy can be safely omitted. METHODS: We evaluated the risk of lymph node metastasis (LNM) using LNM score (histological grade, tumor volume measured in magnetic resonance imaging [MRI], and serum CA-125), myometrial invasion and extrautrerine spread assessed by MRI. Fifty-six patients of which LNM score was 0 and myometrial invasion was less than 50% were consecutively enrolled in the study in which a lymphadenectomy was initially intended not to perform. We analyzed several histological findings and investigated the recurrence rate and overall survival. RESULTS: Fifty-one patients underwent surgery without lymphadenectomy. Five (8.9%) who had obvious myometrial invasion intraoperatively underwent systematic lymphadenectomy. One (1.8%) with endometrial cancer which was considered to arise from adenomyosis had para-aortic LNM. Negative predictive value of deep myometrial invasion was 96.4% (54/56). During the mean follow-up period of 55 months, one patient with deep myometrial invasion who refused an adjuvant therapy had tumor recurrence. The overall survival rate was 100% during the study period. CONCLUSION: This preoperative assessment is useful to select the early stage endometrial cancer patients without risk of LNM and to safely omit lymphadenectomy.

A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer.

OBJECTIVE: To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (>1cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer. METHODS: This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed. RESULTS: From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p=0.01); CA-125 ≥ 500 U/mL (p<0.001); ASA 3-4 (p<0.001); suprarenal retroperitoneal lymph nodes >1cm (p<0.001); diffuse small bowel adhesions/thickening (p<0.001); and lesions >1cm in the small bowel mesentery (p=0.03), root of the superior mesenteric artery (p=0.003), perisplenic area (p<0.001), and lesser sac (p<0.001). A 'predictive value score' was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1-2, 3-4, 5-6, 7-8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758. CONCLUSIONS: We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment.

Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials.

PURPOSE: The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer. METHODS: A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location. RESULTS: Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA. CONCLUSION: Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer.

Krüppel-like factor 17 (KLF17), a member of the KLF transcription factor family, has been shown to inhibit the epithelial-mesenchymal transition (EMT) and tumor growth. However, the expression, the cellular function and the mechanism of KLF17 in endometrioid endometrial cancer (EEC; a dominant type of endometrial cancer) remain elusive. Here, we report that among the KLF family members, KLF17 was consistently upregulated in EEC cell lines compared with immortalized endometrial epithelial cells. Overexpression of KLF17 in EEC cell lines induced EMT and promoted cell invasion and drug resistance, resulting in increased expression of TWIST1. In contrast, KLF17 suppression reversed EMT, diminished cell invasion, restored drug sensitivity and suppressed TWIST1 expression. Luciferase assays, site-directed mutagenesis and transcription factor DNA-binding analysis demonstrated that KLF17 transactivates TWIST1 expression by directly binding to the TWIST1 promoter. Knockdown of TWIST1 prevented KLF17-induced EMT. Consistent with these results, both KLF17 and TWIST1 levels were found to be elevated in EECs compared with normal tissues. KLF17 expression positively correlated with tumor grade but inversely correlated with estrogen and progesterone receptor expression. Thus, KLF17 may have an oncogenic role during EEC progression via initiating EMT through the regulation of TWIST1.

Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer.

PURPOSE: To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer. METHODS: A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces). RESULTS: Of the 89 PET scans, 52 (58.4%) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2% of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of ≥12 months had such disease (P = 0.0031). CONCLUSION: PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of ≥12 months are the best candidates for cytoreductive surgery.

Multivariate prognostic analysis of adenocarcinoma of the uterine cervix treated with radical hysterectomy and systematic lymphadenectomy.

OBJECTIVE: The aim of this study was to investigate the prognostic factors and treatment outcome of patients with adenocarcinoma of the uterine cervix who underwent radical hysterectomy with systematic lymphadenectomy. METHODS: A total of 130 patients with stage IB to IIB cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy from 1982 to 2005 were retrospectively analyzed. Clinicopathological data including age, stage, tumor size, the number of positive node sites, lymphovascular space invasion, parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion, vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were collected and Cox regression analysis was used to determine independent prognostic factors. RESULTS: An estimated five-year survival rate of stage IB1 was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB. Prognosis of patients with one positive-node site is similar to that of those with negative-node. Prognosis of patients with multiple positive-node sites was significantly poorer than that of negative and one positive-node site. Multivariate analysis revealed that lymph node metastasis, lymphovascular space invasion, and parametrial invasion were independent prognostic factors for cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was stratified into three groups by the combination of three independent prognostic factors. CONCLUSION: Lymph node metastasis, lymphovascular space invasion, and parametrial invasion were shown to be independent prognostic factors for cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy.

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women.

We examined incidence probabilities of cervical intraepithelial neoplasia 3 (CIN3) or more severe lesions (CIN3+) in 1,467 adult Japanese women with abnormal cytology in relation to seven common human papillomavirus (HPV) infections (16/18/31/33/35/52/58) between April 2000 and March 2008. Sixty-seven patients with multiple HPV infection were excluded from the risk factor analysis. Incidence of CIN3+ in 1,400 patients including 68 with ASCUS, 969 with low grade squamous intraepithelial lesion (LSIL), 132 with HSIL without histology-proven CIN2 (HSIL/CIN2(-)) and 231 with HSIL with histology-proven CIN2 (HSIL/CIN2(+)) was investigated. In both high grade squamous intraepithelial lesion (HSIL)/CIN2(-) and HSIL/CIN2(+), HPV16/18/33 was associated with a significantly earlier and higher incidence of CIN3+ than HPV31/35/52/58 (p = 0.049 and p = 0.0060, respectively). This association was also observed in LSIL (p = 0.0002). The 1-year cumulative incidence rate (CIR) of CIN3+ in HSIL/CIN2(-) and HSIL/CIN2(+) according to HPV genotypes (16/18/33 vs. 31/35/52/58) were 27.1% vs. 7.5% and 46.6% vs. 19.2%, respectively. In contrast, progression of HSIL/CIN2(+) to CIN3+ was infrequent when HPV DNA was undetected: 0% of 1-year CIR and 8.1% of 5-year CIR. All cervical cancer occurred in HSIL cases of seven high-risk HPVs (11/198) but not in cases of other HPV or undetectable/negative-HPV (0/165) (p = 0.0013). In conclusion, incidence of CIN3+ depends on HPV genotypes, severity of cytological abnormalities and histology of CIN2. HSIL/CIN2(+) associated with HPV16/18/33 may justify early therapeutic intervention, while HSIL/CIN2(-) harboring these HPV genotypes needs close observation to detect incidence of CIN3+. A therapeutic intervention is not indicated for CIN2 without HPV DNA.