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1.
J Surg Oncol ; 118(4): 687-693, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30206937

ABSTRACT

BACKGROUND AND OBJECTIVES: The optimum treatment strategy for patients with unresectable advanced epithelial ovarian cancer is controversial. This study examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus carboplatin), followed by interval debulking surgery (IDS), for these patients. METHODS: In a prospective nonrandomized study, newly diagnosed patients received four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The primary endpoint was the complete resection rate at IDS. Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications. RESULTS: Twenty-three patients were enrolled. The complete resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%). The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events ≥ grade 3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation. Grade 2 complications of IDS included lymphatic complications (13.6%), infections (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic complications, fistula/abscess, or perforation/anastomotic leak, and no complications ≥ grade 3. CONCLUSIONS: In Japanese patients with advanced ovarian cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further investigation of its prognostic effect is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures/methods , Neoadjuvant Therapy , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Adult , Aged , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Combined Modality Therapy , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Prognosis , Prospective Studies , Safety
2.
J Obstet Gynaecol Res ; 44(7): 1330-1334, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29767464

ABSTRACT

Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin. In 2014, recurrence was detected again, but CR was achieved by third-line combination therapy with gemcitabine, carboplatin and bevacizumab. In 2015, the third recurrence was found during bevacizumab maintenance therapy. Fourth-line treatment was initiated with BEV + GEM, which has maintained stable disease for 29 months. This is the first report about marked prolongation of survival by BEV + GEM in a patient with platinum-resistant recurrent ovarian cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Platinum/pharmacology , Aged , Female , Humans , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/surgery
3.
Int J Gynecol Cancer ; 28(4): 657-665, 2018 05.
Article in English | MEDLINE | ID: mdl-29324533

ABSTRACT

OBJECTIVE: We conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC). METHODS: At 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma. RESULTS: There were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter. CONCLUSIONS: This study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.


Subject(s)
Carcinoma/diagnosis , Peritoneal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma/epidemiology , Carcinoma/therapy , Female , Humans , Japan/epidemiology , Middle Aged , Peritoneal Neoplasms/epidemiology , Peritoneal Neoplasms/therapy , Retrospective Studies
4.
Am J Case Rep ; 18: 919-925, 2017 Aug 24.
Article in English | MEDLINE | ID: mdl-28835604

ABSTRACT

BACKGROUND Paraovarian cysts are common and are generally benign; however, they are frequently misdiagnosed as being of ovarian origin. Conversely, paraovarian tumors of borderline malignancy are extremely rare. Especially, no cases of spontaneous rupture have been reported, and all previous reports had normal serum carbohydrate antigen (CA) 125 level. As for imaging findings, the presence of papillary projections in the lumen of paraovarian tumors does not always indicate malignancy or benignancy, which makes the preoperative distinction difficult. CASE REPORT We report a case involving a 22-year-old Asian woman with a spontaneously ruptured paraovarian tumor of borderline malignancy. The serum CA125 concentration was extremely elevated, at 28,831 U/mL. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a collapsed unilocular cystic lesion with multiple papillary projections. On MRI, the papillary projections showed two different patterns, which corresponded to the pathological findings. CONCLUSIONS Ruptured paraovarian tumors of borderline malignancy may show extremely high serum CA125 values. Furthermore, specific MRI findings may be useful in evaluating the malignancy of paraovarian tumors.


Subject(s)
CA-125 Antigen/blood , Ovarian Cysts/diagnostic imaging , Ovarian Cysts/pathology , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Female , Humans , Rupture, Spontaneous , Young Adult
5.
Int J Gynecol Cancer ; 27(2): 267-273, 2017 02.
Article in English | MEDLINE | ID: mdl-28114234

ABSTRACT

OBJECTIVES: Sulfatide has been shown to be characteristically increased on the apical surface of the normal endometrium at the secretory phase, and to be related with the formation of the glandular structure and the secretion of mucin from glands for the implantation of a fertilized egg. Additionally, sulfatides are expressed in the well-differentiated type, but not in the poorly differentiated type, of endometrial carcinomas. This suggests that sulfatides are a molecular marker of differentiated phenotypes. To further elucidate the biological significance of sulfoglycolipids, we transfected the sulfotransferase gene into endometrial carcinoma-derived cells without sulfoglycolipids and compared their glycolipid compositions and phenotypes with those of the original cells. MATERIALS AND METHODS: The glycolipid sulfotransferase gene was transfected into endometrial carcinoma-derived SNG-II cells, the resultant transfected cells being found to frequently form a domelike structure, and some of them were selected as SNG-II-GST cells. We compared the glycolipid compositions and phenotypes of SNG-II and SNG-II-GST cells. RESULTS: Although the original SNG-II cells grew in a paving stone pattern, SNG-II-GST cells formed a domelike structure. SNG-II-GST cells exhibited high GST activity and contained sulfoglycolipids, IISO3-LacCer and IISO3-Gg3Cer, which were not found in SNG-II cells. The amounts of sulfoglycolipids in SNG-II-GST cells were 1.5 times higher than those of gangliosides, and the proportions of LacCer and GM3 in SNG-II-GST cells were greatly different from those in SNG-II cells. SNG-II and SNG-II GST cells exhibited poorly differentiated and well-differentiated phenotypes on histochemical examination of cancerous nodules in nude mice. However, by means of an oxygen electrode, SNG-II-GST cells were found to be more resistant to anticancer drugs than SNG-II cells. CONCLUSION: Enhanced expression of sulfoglycolipids in poorly differentiated cells is a feasible means of selecting well-differentiated ones, and sulfoglycolipids are involved in the well-differentiated phenotype like those in the normal endometrium at the secretory phase.


Subject(s)
Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Glycolipids/metabolism , Sulfotransferases/genetics , Animals , Cattle , Cell Differentiation/physiology , Cell Line, Tumor , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/metabolism , Female , Humans , Paclitaxel/pharmacology , Phenotype , Rats , Sulfotransferases/metabolism , Transfection/methods
6.
J Cancer ; 7(8): 890-9, 2016.
Article in English | MEDLINE | ID: mdl-27313778

ABSTRACT

[Objective] To achieve less invasive lymphadenectomy in endometrial cancer patients, we performed extraperitoneal pelvic and para-aortic lymphadenectomy via a small midline abdominal incision with retroperitoneal approach. The feasibility and safety of this method were investigated. [Methods] Inclusion criteria were 1) endometrioid adenocarcinoma diagnosed by preoperative biopsy, 2) myometrial invasion by magnetic resonance imaging, and 3) no peritoneal dissemination or distant metastasis by computed tomography. Systematic extraperitoneal dissection of pelvic and para-aortic lymph nodes was performed via an approximately 12-cm midline lower abdominal incision, after which hysterectomy and bilateral salpingo-oophorectomy were done (extraperitoneal group). The historical control group was patients who underwent standard transperitoneal lymphadenectomy followed by hysterectomy and bilateral salpingo-oophorectomy. The two groups were compared for demographic characteristics, perioperative factors, and complications. [Results] A total of 62 patients were enrolled. Demographic and clinicopathological factors showed no differences between the extraperitoneal group (n = 34) and the historical control group (n = 28). The median number of pelvic (30 vs. 28) and para-aortic (14 vs. 17) nodes dissected was also similar. However, median intraoperative blood loss was significantly smaller in the extraperitoneal group than the control group (220 vs. 573 g). Median operating time (265 vs. 323.5 min), median laparotomy time (60 vs. 295 min), and median initial flatus time (8 vs. 32 hours) were all significantly shorter in the extraperitoneal group, while complications and severe postoperative pain were significantly less frequent. [Conclusions] Our new technique was feasible, safe, and less invasive than standard laparotomy. It is an alternative to laparoscope-assisted or robotic procedures.

7.
Int J Clin Oncol ; 21(3): 419-34, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27116188

ABSTRACT

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.


Subject(s)
Lymph Node Excision , Neoplasm Recurrence, Local/therapy , Trophoblastic Neoplasms/therapy , Uterine Neoplasms/therapy , Algorithms , Aorta , Female , Fertility Preservation , Hormone Replacement Therapy , Humans , Hysterectomy , Japan , Laparoscopy , Pelvis
8.
Reprod Sci ; 22(12): 1509-15, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26092278

ABSTRACT

We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions.


Subject(s)
DNA, Viral/genetics , Human Papillomavirus DNA Tests , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Squamous Intraepithelial Lesions of the Cervix/diagnosis , Triage/methods , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Age Distribution , Age Factors , Asian People , DNA, Viral/isolation & purification , Female , Humans , Japan/epidemiology , Middle Aged , Neoplasm Grading , Papillomaviridae/isolation & purification , Papillomavirus Infections/ethnology , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Predictive Value of Tests , Prevalence , Risk Assessment , Risk Factors , Squamous Intraepithelial Lesions of the Cervix/ethnology , Squamous Intraepithelial Lesions of the Cervix/pathology , Squamous Intraepithelial Lesions of the Cervix/virology , Unnecessary Procedures , Uterine Cervical Neoplasms/ethnology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/ethnology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
9.
J Obstet Gynaecol Res ; 41(9): 1449-56, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26013736

ABSTRACT

AIM: To evaluate the efficacy and safety of Kampo therapy based on Goreisan for lower abdominal lymphedema after surgical treatment of endometrial cancer or cervical cancer. METHODS: Radical surgery, including retroperitoneal lymphadenectomy, was performed for endometrial cancer and cervical cancer. After surgery, Kampo therapy based on Goreisan and integrated physical therapy were provided for patients with lower abdominal lymphedema, especially lymphedema affecting the pubic-inguinal-vulval region. Goreisan (7.5 g/day) was given orally three times a day (tds). If a significant response was not observed, Saireito (9 g/day; 3 g tds) or Gosyajinkigan (7.5 g/day; 2.5 g tds) was administered concomitantly. RESULTS: A total of 21 patients received treatment. The response rate to Goreisan monotherapy was 78%, with 22% being non-responders. Median reduction of abdominal circumference was 2.1cm (95% CI 1.3-2.85). When Goreisan was combined with another Kampo agent, the response rate was 92% and the non-response rate was 8%. The median reduction of the abdominal circumference was 2.85 cm (95% CI: 2.25-3.3). In particular, concomitant Goreisan and Saireito therapy achieved satisfactory results. No severe adverse reactions occurred. CONCLUSIONS: Goreisan-based Kampo therapy might be effective and safe for lower abdominal lymphedema after retroperitoneal lymphadenectomy. We will perform a prospective control study in the near future.


Subject(s)
Lymph Node Excision/adverse effects , Lymphedema/therapy , Medicine, Chinese Traditional/methods , Medicine, Kampo/methods , Physical Therapy Modalities , Postoperative Complications/therapy , Adult , Drainage , Endometrial Neoplasms/surgery , Feasibility Studies , Female , Humans , Lymph Node Excision/methods , Lymphedema/etiology , Middle Aged , Postoperative Complications/etiology , Treatment Outcome , Uterine Cervical Neoplasms/surgery
10.
Int J Clin Oncol ; 20(1): 134-42, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24744261

ABSTRACT

BACKGROUND: p16(INK4a) immunohistochemistry has revealed a high rate of positivity in cervical intraepithelial neoplasia grade 2 (CIN2) and more severe conditions (CIN2+). The Lower Anogenital Squamous Terminology Standardization project proposed p16(INK4a) immunohistochemistry as an ancillary test for CIN. Immunocytochemistry involving dual staining for p16(INK4a) and Ki-67 in the triage of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) is reported to be useful in the identification of CIN2+. However, it is unclear whether p16(INK4a)/Ki-67 immunocytochemistry is of practical relevance for the triage of ASCUS and LSIL in the Japanese screening system. METHODS: From 427 women fulfilling the eligibility criteria, 188 ASCUS and 239 LSIL specimens were analyzed. The accuracy of p16(INK4a)/Ki-67 immunocytochemistry and genotyping of high-risk human papillomaviruses (HPVs) in detecting CIN2+ were compared. RESULTS: p16(INK4a)/Ki-67 immunocytochemistry was positive in 33.5 % (63/188) of ASCUS, and 36.8 % (88/239) of LSIL specimens. The sensitivity and specificity of p16(INK4a)/Ki-67 immunocytochemistry was 87.3 % (95 % confidence interval 78.0-93.8 %) and 76.4 % (71.6-80.8 %), respectively. The positive and negative predictive values were 45.7 % (37.6-54.0 %) and 96.4 % (93.4-98.3 %), respectively; positive and negative likelihood ratios were 3.71 and 0.17, respectively. Using the McNemar test, p16(INK4a)/Ki-67 immunocytochemistry showed equivalent sensitivity but higher specificity than the HPV genotyping test CONCLUSIONS: Compared with high-risk HPV genotyping, p16(INK4a)/Ki-67 immunocytochemistry was a more accurate triage test for identifying CIN2+ in ASCUS and LSIL specimens.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16/immunology , Ki-67 Antigen/immunology , Squamous Intraepithelial Lesions of the Cervix/diagnosis , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Asian People , Atypical Squamous Cells of the Cervix , Female , Genotype , Humans , Immunohistochemistry/methods , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/pathology , Sensitivity and Specificity , Squamous Intraepithelial Lesions of the Cervix/pathology , Uterine Cervical Neoplasms/pathology , Young Adult , Uterine Cervical Dysplasia/pathology
11.
J Virol Methods ; 204: 73-80, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24768623

ABSTRACT

Regional differences in human papillomavirus (HPV) genotypes and the presence of mixed HPV infections may affect adversely the efficacy of the HPV vaccine. Therefore, a simple and high-throughput HPV genotyping system is required. Recently, a novel HPV genotyping kit (the Mebgen™ HPV kit) was developed. This kit uses multiplex PCR and Luminex xMAP™ technology to detect 13 types of high-risk HPVs and an internal control in a 96-well format. In the present study, the analytical performance of the kit was examined using HPV plasmid DNA. All 13 types of HPVs were detected with a minimum detection sensitivity of 250 copies/test, and highly specific signals were observed. HPV 16 plasmid was detected in samples containing mixtures with other HPV-type plasmids in ratios ranging from 1:1 to 1:1000. No cross reactivity was observed with DNA from 27 types of other infectious microbes. A clinical evaluation was carried out using cervical samples from 356 patients with persistent abnormal smears diagnosed at mass public health screenings for cervical cancer. The samples were preserved in Tacas™ medium until analysis. HPV was detected in 162 (45.5%) samples including 110 (67.9%) with single infections and 52 (32.1%) with multiple infections. The type distribution of the 13 high-risk HPVs was as follows: 28.4% HPV 16, 11.7% HPV 18, 6.8% HPV 31, 3.1% HPV 33, 3.7% HPV 35, 9.3% HPV 39, 1.9% HPV 45, 8.6% HPV 51, 37.0% HPV 52, 9.3% HPV 56, 16.7% HPV 58, 3.7% HPV 59, and 1.9% HPV 68. To evaluate sample stability over time, changes in the detection of HPV DNA derived from HeLa and SiHa cells were measured in 3 types of liquid-based cytology media. HPV DNA was detected in Tacas and Thinprep™ samples after storage at 4°C or 30°C for 4 weeks and within 1 week of collection in Surepath™ samples. These results suggest that this newly developed HPV genotyping kit is suitable for use in both clinical applications and large-scale epidemiological studies.


Subject(s)
Genotyping Techniques/methods , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/virology , Adult , Aged , Aged, 80 and over , Coinfection/virology , Female , Humans , Middle Aged , Papillomaviridae/isolation & purification , Specimen Handling/methods , Temperature , Time Factors , Young Adult
12.
Int J Gynecol Pathol ; 32(5): 464-70, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23896708

ABSTRACT

Ovarian pulmonary-type small cell carcinoma is a rare and extremely aggressive neoplasm. We report the occurrence of an ovarian small cell carcinoma of pulmonary type in a 54-year-old woman. She underwent a total abdominal hysterectomy with a bilateral salpingo-oophorectomy and infracolic omentectomy. A diagnosis of stage IIIA pulmonary-type small cell carcinoma was rendered. The tumor appeared to be composed of a solid growth of small cells arranged in sheets and closely packed nests with insular arrangements separated by a fibrous stroma. The tumor cells had hyperchromatic nuclei with inconspicuous nucleoli and scanty cytoplasm. Rosette and rosette-like structures were scattered. Immunohistochemical staining showed positivity for synaptophysin, neural cell adhesion molecule (NCAM), and focally for chromogranin. Cytokeratin and neuron-specific enolase (NSE) were also positive. Over 80% of the tumor cells showed strong reactivity for MIB-1. Electron microscopy showed neuroendocrine granules. She was effectively treated with paclitaxel plus carboplatin after the surgery.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Neuroendocrine/pathology , Carcinoma, Small Cell/pathology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Carboplatin/therapeutic use , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/surgery , Carcinoma, Ovarian Epithelial , Carcinoma, Small Cell/diagnostic imaging , Carcinoma, Small Cell/surgery , Carrier Proteins/metabolism , Female , Humans , Keratins/metabolism , Lung/pathology , Middle Aged , Neoplasms, Glandular and Epithelial/diagnostic imaging , Neoplasms, Glandular and Epithelial/surgery , Neural Cell Adhesion Molecules/metabolism , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/surgery , Paclitaxel/therapeutic use , Tomography, X-Ray Computed , Ubiquitin-Protein Ligases/metabolism
13.
J Gynecol Oncol ; 24(3): 215-21, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23875070

ABSTRACT

OBJECTIVE: In cervical intraepithelial neoplasia (CIN), p16(INK4a) immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16(INK4a) immunohistochemistry and the outcomes of CIN. Here, we report p16(INK4a) immunohistochemistry as an effective biomarker to predict the outcomes of CIN. METHODS: p16(INK4a) immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16(INK4a) expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes. RESULTS: A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16(INK4a) overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16(INK4a) overexpression than for those not showing p16(INK4a) overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16(INK4a) overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively). CONCLUSION: p16(INK4a) overexpression was correlated with the outcome of CIN 1-2, and p16(INK4a) is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.

15.
J Gynecol Oncol ; 23(3): 153-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22808357

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. METHODS: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. RESULTS: The median follow-up period was 64.3 months. The depth of stromal invasion was ≤3 mm in 33 cases and >3 mm, but ≤5 mm in 17 cases. The horizontal spread was ≤7 mm in 25 cases and >7 mm in 25 cases. One of the 33 cases that had tumor volumes of ≤500 mm(3), and three of the 17 cases with tumor volumes of >500 mm(3) were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p<0.0001). The frequency of pelvic lymph node metastases was significantly higher in the lymphovascular space invasion (LVSI)-positive group than in the LVSI-negative group (p=0.02). No adnexal metastasis or parametrial involvement was noted. CONCLUSION: Assessment of the depth of stromal invasion, tumor volume, and LVSI is critical for selecting an appropriate therapeutic modality. Non-radical methods of management are considered suitable for patients with LVSI-negative adenocarcinoma of the cervix exhibiting a stromal invasion depth of ≤5 mm and a tumor volume of ≤500 mm(3).

16.
Oncol Rep ; 28(2): 487-93, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22614251

ABSTRACT

The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma. Eligibility included patients who received irinotecan (60 mg/m2) on days 1 and 8 and nedaplatin (80 mg/m2) on day 1 of a 21-day cycle. After 1-3 courses of chemotherapy, radical hysterectomy was performed. Sixty-eight patients were enrolled. Sixty-six were included in the full analysis set. Their median age was 47 years (range 22-71), the FIGO stage was Ib2 in 18 patients, IIa in 10, and IIb in 38. Radical hysterectomy was performed after NAC in 63 patients (95.5%). The number of administered courses of NAC was 1 in 13 patients, 2 in 43, and 3 in 10. The response rate, the primary endpoint of this study, was 75.8% (CR in 2 patients, PR in 48, SD in 12, PD in 0, and NE in 4). The mean number of treatment courses required for a response was 1.42 (1 course in 30 patients, 2 courses in 19, and 3 courses in 1). The incidences of grade 3 or 4 hematological toxicities were: neutropenia 72.2%, leukopenia 16.7%, anemia 13.6%, thrombocytopenia 7.6%, febrile neutropenia 1.5%, and elevations of alanine aminotransferase and aspartate aminotransferase 1.5%. Grade 3 or 4 non-hematologic toxicities were as follows: diarrhea 6.1%, nausea 3%, anorexia 1.5%, vomiting 1.5%, fever 1.5%, allergic reactions 1.5%, ileus 1.5% and vesicovaginal fistula 1.5%. Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/surgery , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Carcinoma, Squamous Cell/pathology , Chemotherapy, Adjuvant , Female , Humans , Hysterectomy/methods , Irinotecan , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Uterine Cervical Neoplasms/pathology , Young Adult
17.
Hum Cell ; 24(3): 115-20, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21656277

ABSTRACT

Cell profiles determined by the thin-layer advanced cytology assay system (TACAS™), a liquid-based cytology technique newly developed in Japan, were analyzed in this study. Hybrid capture 2 (HC-2) was also performed using the liquid-based samples prepared by TACAS to ascertain its ability to detect human papillomavirus (HPV). Cell collection samples from uterine cervix were obtained from 359 patients and examined cytologically. A HC-2 assay for HPV was carried out in the cell specimens. All specimens were found to show background factors such as leukocytes. After excluding the 5 unsatisfactory cases from the total 354 cases, 82 cases (23.2%) were positive and 272 cases (76.8%) were negative for HPV. Cell specimens from 30 HPV-positive cases and 166 HPV-negative cases were subjected to 4 weeks of preservation at room temperature. Then, when subsequently re-assayed, 28 cases (93.3%) in the former group were found to be HPV positive and 164 cases (98.8%) in the latter group were found to be HPV negative. These results supported the excellent reproducibility of TACAS for HPV testing. A reasonable inference from the foregoing analysis is that TACAS may be distinguished from other liquid-based cytological approaches, such as ThinPrep and SurePath, in that it can retain the cell backgrounds. Furthermore, this study raises the possibility that cell specimens prepared using TACAS could be preserved for at least 4 weeks prior to carrying out a HC-2 assay for HPV.


Subject(s)
Cervix Uteri/virology , Cytological Techniques/methods , Early Detection of Cancer/methods , Papillomaviridae/isolation & purification , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Female , Humans , Reproducibility of Results , Time Factors
18.
J Minim Invasive Gynecol ; 18(2): 257-61, 2011.
Article in English | MEDLINE | ID: mdl-21354075

ABSTRACT

Adenomatoid tumors are rare benign mesothelial tumors of the genital tract, and only a few cases of uterine adenomatoid tumors treated at laparoscopic surgery have been reported. Herein is reported the case of a laparoscopically resected uterine adenomatoid tumor with coexisting endometriosis. A 34-year-old nulliparous woman with suspected uterine fibroma and endometrial cysts underwent laparoscopic surgery in which both the uterine tumor and the endometrial cysts were enucleated. Enucleation of the uterine tumor was difficult, and, therefore, the border between the tumor and normal myometrium was divided using a harmonic scalpel for tumor resection. Microscopic examination of the tumor showed irregularly proliferating smooth muscle cells and many round hiatuses lined by epithelial-like cells. These epithelial-like cells were immunohistochemically positive for mesothelin and podoplanin, and negative for CD34, which suggests that the tumor was an adenomatoid tumor. This may be the fourth reported case of an adenomatoid tumor resected using the laparoscopic approach.


Subject(s)
Adenomatoid Tumor/surgery , Endometriosis/surgery , Ovarian Diseases/surgery , Uterine Neoplasms/surgery , Adenomatoid Tumor/complications , Adenomatoid Tumor/pathology , Adult , Endometriosis/complications , Endometriosis/pathology , Female , Gynecologic Surgical Procedures , Humans , Laparoscopy , Ovarian Diseases/complications , Ovarian Diseases/pathology , Treatment Outcome , Uterine Neoplasms/complications , Uterine Neoplasms/pathology
19.
J Obstet Gynaecol Res ; 37(5): 468-71, 2011 May.
Article in English | MEDLINE | ID: mdl-21272150

ABSTRACT

Atypical polypoid adenomyoma is a rare uterine tumor composed of atypical endometrial glands, which often exhibit squamous metaplasia, and a cellular smooth muscle stroma. Although atypical polypoid adenomyoma is categorized as a benign lesion, it is reportedly associated with endometrial cancer, and it shows persistence and recurrence even after conservative medical treatment. We present a rare case of atypical polypoid adenomyoma that possibly underwent a serial pathological change from endometrial hyperplasia to carcinoma in a 40-year-old woman with no history of pregnancy. She was diagnosed with atypical polypoid adenomyoma during polypectomy surgery. After resecting the atypical polypoid adenomyoma, endometrial hyperplasia complex was detected. This condition eventually progressed from atypical hyperplasia complex to endometrial adenocarcinoma, and total abdominal hysterectomy was performed. A patient with atypical polypoid adenomyoma who wishes to preserve her fertility should be carefully monitored for endometrial carcinoma. If endometrial hyperplasia is detected in such a patient, a meticulous follow-up examination by performing endometrial biopsy is mandatory.


Subject(s)
Adenomyoma/diagnosis , Uterine Neoplasms/diagnosis , Adenomyoma/pathology , Adenomyoma/surgery , Adult , Diagnosis, Differential , Disease Progression , Endometrial Hyperplasia/diagnosis , Endometrial Hyperplasia/pathology , Female , Humans , Hysterectomy , Uterine Neoplasms/pathology , Uterine Neoplasms/surgery
20.
Hum Cell ; 23(4): 126-33, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21166883

ABSTRACT

We compared the detection rate of cervical neoplasias between a liquid-based cytology (LBC) method using SurePath and the conventional method. We also studied the feasibility of human papillomavirus (HPV) typing by linear array assay. Cytological specimens from 1551 Japanese women were prepared using the conventional and SurePath methods; the cytological and histological results from biopsy samples were compared. HPV typing using an HPV linear array assay was carried out on residual specimens using the SurePath method. The cytodiagnostic results showed a concordance rate of 85.3% (Κ= 0.46) between the two methods. The sensitivity of lesions histopathologically diagnosed as CIN1 or above was not significantly different between the two methods (P = 0.575-1.000). The receiver operating characteristic curve analysis of the detectability in CIN2 or above revealed no significant difference between the two methods (P = 0.096). Among the 44 patients who underwent HPV typing using a linear array assay, 33 samples were eligible for HPV testing and were stored at ambient temperature. In conclusion, the SurePath and conventional methods have equivalent abilities for detecting cervical lesions. After preparation for cytological diagnosis, use of the remaining cells from the SurePath specimens to perform HPV typing using the linear array method could be feasible.


Subject(s)
Alphapapillomavirus/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/virology , Cytodiagnosis/methods , Genotype , Papillomavirus Infections/virology , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Adult , Aged , Female , Humans , Japan , Middle Aged
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