Do we need a different strategy for HPV screening and vaccination in East Asia?
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Asia, Eastern↗
Biomedical subjects
Hajime Tsunoda
Publications and source records attributed to Hajime Tsunoda.
Phenotypic characterization of endometrial stromal sarcoma of the uterus.
Endometrial stromal sarcoma (ESS) of the uterus is a rare uterine malignancy that has not been characterized in detail. To characterize the phenotype of ESS of the uterus, we extracted RNA from ESS and the stroma of normal endometrium using a tissue microdissection system and compared the expression profiles in the two tissues. After suppression subtractive hybridization and differential screening, we detected the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene as one of the major genes upregulated in ESS, and a full-length placental cDNA clone (CS0DI066YJ10) as one of the major genes downregulated. The results were confirmed by in situ hybridization in four resected specimens of ESS and 36 biopsy specimens of normal endometrial tissue. All ESS (4/4) and all cases of endometrial stromal cells in the proliferative phase (13/13) were positive for MALAT-1, but samples of normal stroma in the secretory phase and menopausal state included some that were negative or weakly positive for MALAT-1 (5/13 and 3/10, respectively). In contrast, all ESS and 12 of 13 cases of stromal cells in the proliferative phase were negative for the full-length placental cDNA clone but 10 of 13 cases of endometrial stromal cells in the secretory phase were positive for transcripts of the gene (P < 0.05). These results indicated that endometrial stromal cells have different phenotypic characteristics between proliferative and secretory phases and the tumor cells of ESS have the phenotypic character of endometrial stromal cells in the proliferative phase.
Cell Proliferation↗
Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors.
PURPOSE: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. METHODS AND MATERIALS: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day(-1)) of the shrinkage curve by fitting to an exponential equation. RESULTS: Early-assessed radioresponse ranged from 0.001 to 0.106 day(-1) (median, 0.021 day(-1)) and late-assessed radioresponse from 0.009 to 0.091 day(-1) (median, 0.021 day(-1)), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R(2) = 0.714, p = 0.0005). CONCLUSIONS: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.
Adult↗
Successful diagnosis of thromboembolism before surgery in a woman with clear cell adenocarcinoma of the endometrium.
Patients with ovarian cancer with clear cell histology often have venous thromboembolism (VTE) even before surgery. In view of the possible association between clear cell histology and VTE in endometrial cancer, we measured the plasma levels of thrombin-antithrombin III complex (TAT) and D-dimer (DD) in the preoperative examinations of a patient with clear cell adenocarcinoma of the endometrium. Plasma TAT and DD were both highly elevated, though the patient had no symptoms of VTE or risk factors such as obesity or diabetes mellitus. Ultrasound Doppler examination and lung perfusion scintigraphy just before surgery revealed a thrombosis in the left popliteal vein and a pulmonary embolism. After implanting an inferior vena cava filter to prevent a fatal embolism of the lung, we performed abdominal total hysterectomy, bilateral salpingo-oophorectomy, and sampling of the pelvic lymph nodes. The VTE gradually disappeared and the plasma levels of TAT and DD returned to normal after surgery. Possibly, the VTE in this patient may have been associated with the clear cell histology.
Adenocarcinoma, Clear Cell↗
Microsatellite instability and expression of mismatch repair genes in sporadic endometrial cancer coexisting with colorectal or breast cancer.
The molecular background of sporadic endometrial cancer coexisting with colorectal or breast cancer is not clear. We investigated microsatellite instability (MSI) and status of mismatch repair (MMR) gene product, MLH1, MSH2 and MSH6, in 63 sporadic endometrial cancers coexisting with colorectal or breast cancer. Sixteen sporadic endometrial cancers with colorectal cancers (EC), 26 sporadic endometrial cancers with breast cancer (EB) and 21 endometrial cancers without a coexisting cancer (control) were analyzed. EC had the highest frequency of MSI among the 3 groups (EC, 69%; EB, 23%; and control, 43%). Incidence of low-frequency MSI was significantly higher in EC (38%). Among endometrial cancer cases diagnosed before age 50, all high-frequency MSI (MSI-H) cases belonged to EC. Interestingly, incidence of MSI-H was significantly higher in tamoxifen-non-treated cases (75%) than that of treated cases (14%). These results suggest that alterations in MMR genes appear to be involved in carcinogenesis of EC but seem to be uncommon in those of EB. Presence of MSI in sporadic endometrial cancer may be a useful marker to predict the risk of colorectal cancer.
Adaptor Proteins, Signal Transducing↗
Preliminary estimation of treatment effect on uterine cervical squamous cell carcinoma in terms of tumor regression rate: comparison between chemoradiotherapy and radiotherapy alone.
PURPOSE: We preliminarily estimated the treatment effect on cervical cancer in terms of the tumor regression rate (TRR) achieved with chemoradiotherapy and radiotherapy alone. MATERIALS AND METHODS: The study included cervical squamous cell carcinomas treated by radiotherapy alone (n=45) or chemoradiotherapy (concurrent once-a-week cisplatin 30 mg/m2, n=13). Tumors were measured three-dimensionally on pre- and mid-treatment magnetic resonance images. TRR was defined as the slope of the exponential regression curve of tumor volume (day(-1)) on the assumption that tumors regressed exponentially with time. RESULTS: TRR ranged widely (0.004-0.090 day-(-1)) and did not significantly differ between treatment with chemoradiotherapy (median, 0.032 day(-1)) and with radiotherapy alone (median, 0.024 day(-1)) (p = 0.361). TRR > 0.05 day(-1) was seen in four chemoradiotherapy tumors (30.8%) and in six radiotherapy-alone tumors (15.0%) (p = 0.207), whereas TRR < 0.01 day(-1) was seen in no chemoradiotherapy tumors (0.0%) and in five radiotherapy-alone tumors (11.1%) (p = 0.180). TRR for tumors > 5.0 cm in diameter was greater with chemoradiotherapy (n=5) than with radiotherapy alone (n=12) (p = 0.065). CONCLUSION: Although the difference did not reach a statistically significant level, our TRR data suggest that concurrent chemotherapy heightens the radioresponse of large-size cervical cancer.
Adult↗
Use of the small pelvic field instead of the classic whole pelvic field in postoperative radiotherapy for cervical cancer: reduction of adverse events.
PURPOSE: We examined whether use of small pelvic (SP) field encompassing only the pericervical regions and upper stream lymphatic will reduce the adverse events that occur with classic whole pelvic (WP) field, in postoperative radiotherapy (RT) for cervical cancer. METHODS AND MATERIAL: This retrospective study included 72 patients treated with SP field (SP group) used specifically for node-negative status and 46 patients treated with WP field (WP group) used conventionally for node-positive status. Total dose was 50.0 or 50.4 Gy at 2.0 or 1.8 Gy per fraction. Acute adverse events (nausea, diarrhea, cystitis, and leukopenia) and late adverse events (lymphedema, cystitis, ileus, and diarrhea) were graded according to the Common Toxicity Criteria and compared between groups. RESULTS: Diarrhea (Grades 2-3) and leukopenia (Grades 1-3) occurred significantly more often in WP group (32.4% and 80.5%, respectively) than in SP group (9.2% and 52.2%, respectively). Among the late events, lymphedema occurred most often overall (5-year rate: SP, 47.0%; WP, 49.1%). Only ileus occurred at a significantly higher rate in The WP group than in SP group (5-year rate: 16.2% vs. 3.2%). CONCLUSIONS: Use of the SP field tailored for node-negative status was suggested to reduce adverse events involving the intestine and hemopoietic system.
Adult↗
Smooth muscle tumors of uncertain malignant potential and leiomyosarcomas of the uterus: MR findings.
PURPOSE: To study the MR characteristics of nonbenign uterine smooth muscle tumors. MATERIALS AND METHODS: Nine patients with pathologically proven leiomyosarcomas, and three patients with smooth muscle tumors of uncertain malignant potential (SMTUMP) were included in this study. Twelve cases of benign uterine leiomyomas and variants, in which gynecologists suspected leiomyosarcomas, were also analyzed. In each case we studied the size, location, signal intensity, and contrast enhancement of the tumors. RESULTS: Nine of the 12 nonbenign characters had more than 50% of high-intensity areas on T2-weighted images (T2WI), and some hyperintense foci on T1-weighted images (T1WI). In the contrast study, nine of 12 nonbenign characters had well-demarcated unenhanced areas. On the other hand, only two of 12 benign characters showed such a signal intensity pattern, and none of them had a pocket-like unenhanced area. CONCLUSION: Although there were some exceptions, more than 50% of high signal on T2WI, and the presence of any small high-signal areas on T1WI with unenhanced pockets were considered MR-suggestive for SMTUMPs and leiomyosarcomas.
Adult↗
Complete response to irinotecan hydrochloride and nedaplatin in a patient with advanced ovarian clear cell carcinoma.
A 55-year-old multiparous woman was diagnosed with stage IIIc ovarian clear cell carcinoma. Three years after the first surgery and adjuvant chemotherapy with irinotecan hydrochloride and mitomycin C, she developed common iliac lymph node recurrence. Two cycles of chemotherapy with irinotecan hydrochloride and nedaplatin led to a complete response. Surgical resection revealed pathological complete response. The chemosensitivity of ovarian clear cell carcinoma has been reported to be very poor. No standard chemotherapeutic regimens for this carcinoma have been established. The present study is the first report of a pathological complete response in a patient with advanced ovarian clear cell carcinoma. Future studies are needed to confirm the efficacy of this regimen for this carcinoma.
Adenocarcinoma, Clear Cell↗
Functioning ovarian tumors: direct and indirect findings at MR imaging.
There are many kinds of ovarian tumors and tumorlike conditions that produce estrogen or androgen. Magnetic resonance imaging can demonstrate not only ovarian tumors but also an enlarged uterus with a thick endometrium, even in cases of a clinically latent excess of estrogen. These clinical and indirect imaging findings can aid in the differential diagnosis of ovarian tumors. Granulosa cell tumor and thecoma are well-known estrogen-producing tumors. In pediatric or postmenopausal patients, they manifest as precocious pseudopuberty or postmenopausal bleeding, respectively. Conversely, Sertoli-Leydig cell tumor is representative of hormone-producing tumors that cause virilization. However, there are other functioning ovarian tumors besides the sex cord-stromal tumors. It is well known that metastatic ovarian tumors often have androgen-producing stroma and that mucinous cystadenoma sometimes produces estrogens. Most other ovarian tumors can produce sexual hormones in their stroma. In addition, some endocrinologic abnormalities (eg, polycystic ovary syndrome) also cause virilization.
Adolescent↗
Undifferentiated carcinoma with osteoclast-like multinucleated giant cells arising in an ovarian mature cystic teratoma.
Malignant transformation is an unusual complication of mature cystic teratomas. Squamous cell carcinomas and adenocarcinomas are predominant among these malignant tumors. We present a 70-year-old Japanese woman with a giant ovarian tumor (30 x 23 x 9 cm) and multiple peritoneal dissemination. The huge tumor was filled with necrotic and fatty tissue and coagula accompanied with hair balls histologically diagnosed as undifferentiated carcinoma with multinucleated giant cells arising in an ovarian mature cystic teratoma. The residual disseminated tumors grew very rapidly and occupied the whole abdominal cavity again 3 weeks after the surgery. The patient died 5 weeks after the operation.
Aged↗
Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patterns of treatment failure.
PURPOSE: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether node-negative status could be accurately assessed using a low cutoff measure. METHODS AND MATERIALS: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated. RESULTS: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among node-negative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status. CONCLUSION: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis.
Adult↗
A thickened or indistinct junctional zone on T2-weighted MR images in patients with endometrial carcinoma: pathologic consideration based on microcirculation.
Thickened or indistinct junctional zone (JZ) is a problematic finding in staging endometrial carcinoma. We studied the incidence, pathological cause of this condition correlated to microcirculation, and the utility of dynamic contrast MRI for differential diagnosis. T2-weighted images were analyzed in 119 cases with endometrial carcinoma. The enhancement of the JZ during the dynamic contrast MRI, histopathological causes, and the density of arterioles in the JZ were retrospectively analyzed in cases with thickened or indistinct JZ. The MRI histopathological correlation of all 31 patients with a thickened or indistinct JZ were analyzed, in which it was corresponded to myometrial cancer invasion only in 22%. The sensitivity of a poor early enhancement pattern on dynamic study for detecting myometrial invasion was 71.4%, the specificity was 100%, and the overall accuracy was 92.5%. Although only weak relationship between the contrast enhancement and the arteriole density was revealed, the arteriole density within the JZ with cancer invasion was significantly decreased. Poor enhancement of JZ in early dynamic phase was correlated with the decreased density of arterioles within the myometrium which was invaded by endometrial carcinoma. Dynamic contrast study should be performed in staging endometrial carcinoma especially when JZ was thickened or indistinct.
Endometrial Neoplasms↗
Early acquisition of gelatinolytic activity in carcinogenesis of the uterine cervix.
Film in situ zymography is a newly developed technique for detecting in situ gelatinolytic activity. Using the film in situ zymography method to stamp preparations, we evaluated the gelatinolytic activity in early stage cervical neoplasia and invasive squamous cell carcinoma. To determine the sensitivity of film in situ zymography for detecting gelatinase expression, slides made from stamps of 50 specimens resected from the uterine cervix, including early invasive carcinoma (FIGO Ia1 and Ib1) and cervical intraepithelial neoplasia (CIN) were examined by film in situ zymography. The specimens were also examined immunohistochemically with regard to mitotic activity and gelatinase expression. Gelatinolytic activity was subdivided into two patterns, the homogeneous pattern and the heterogeneous pattern. The homogeneous pattern consisted of circumscribed areas around atypical cell clusters; these areas were composed of homogenously digested full-thickness collagen, whereas the heterogeneous pattern consisted of spottily digested areas of superficial collagen around atypical cell clusters. All invasive carcinomas (8/8 cases) and carcinoma in situ (14/14 cases) were positive for gelatinolytic activity, and 33.3%(5/15 cases) of the specimens of CIN-1, CIN-2, and severe dysplasia were also positive. All invasive carcinomas and 6 of 14 carcinoma in situ (43%) showed homogenous pattern, and the other positive specimens showed heterogenous pattern. The MIB-1 index was 33.8% in invasive carcinoma, increasing stepwise from dysplasia to carcinoma. Matrix metalloproteinase-2 immunostaining was positive in 4 of 8 cases of invasive carcinoma and generally stained the stromal area around the tumor nest. These results indicated that matrix metalloproteinases are functionally activated even in carcinoma in situ and in cervical intraepithelial neoplasia of the uterine cervix not showing invasive growth histologically. Film in situ zymography can detect with sensitivity the invasive potential of carcinoma in situ and cervical intraepithelial neoplasia. An analysis combining cytological examination and film in situ zymography is a potentially useful tool for estimating invasive activity.
Carcinoma↗
Essential role of p38 mitogen-activated protein kinase in contact hypersensitivity.
The present study was designed to elucidate the role of p38 mitogen-activated protein kinase (p38) in the pathogenesis of inflammation, using a mouse contact hypersensitivity (CHS) model induced by 2,4-dinitro-1-fluorobenzene (DNFB). Ear swelling was induced by challenge with DNFB, accompanied by infiltration of mononuclear cells, neutrophils, and eosinophils and a marked increase in mRNA levels of cytokines such as interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-1beta, IL-18, and tumor necrosis factor-alpha in the challenged ear skin. Both ear swelling and the number of infiltrated cells in DNFB-challenged ear skin were significantly inhibited by treatment with SB202190, a p38 inhibitor. Furthermore, the DNFB-induced expression of all cytokines except IL-4 was significantly inhibited by treatment with SB202190. Ribonuclease protection assay revealed that the mRNA levels of chemokines such as IP-10 and MCP-1 in ear skin were markedly increased at 24 h after challenge with DNFB. The induction of these chemokines was significantly inhibited by treatment with SB202190. In p38alpha +/- mice, both ear swelling and infiltration of cells induced by DNFB were reduced compared with those in wild-type mice. However, induction of cytokines by DNFB was also observed in p38alpha +/- mice, although the induction of IFN-gamma, IL-5, and IL-18 was typically reduced compared with that in wild-type mice. Challenge with DNFB slightly induced IP-10 and MCP-1 mRNA in p38alpha +/- mice, with weaker signals than those in SB202190-treated wild-type mice. These results suggest that p38 plays a key role in CHS and is an important target for the treatment of CHS.
Allergens↗
Assessment of cervical cancer radioresponse by serum squamous cell carcinoma antigen and magnetic resonance imaging.
OBJECTIVE: To investigate the possibility of objective clinical assessment of the radioresponse of cervical cancer via determination of serum squamous cell carcinoma antigen levels and magnetic resonance imaging (MRI)-based estimation of tumor shrinkage. METHODS: The cases of 60 patients undergoing definitive radiotherapy for cervical squamous cell carcinoma (stage I-II: n = 20; stage III-IV: n = 40) were reviewed. Measurements of serum squamous cell carcinoma antigen levels (n = 60), estimated tumor volume on preradiotherapy MRIs (n = 60), and evaluated tumor shrinkage on postradiotherapy MRIs available (n = 30) were taken. The relation between postradiotherapy squamous cell carcinoma antigen level 2 months after the start of radiotherapy and disease recurrence was investigated. Regression analysis of tumor volume measured on MRIs was used to estimate the extent of tumor shrinkage 2 months after the start of radiotherapy. RESULTS: Preradiotherapy squamous cell carcinoma antigen levels correlated significantly with preradiotherapy tumor volumes. Recurrence was identified in 27 patients as distant (n = 19), distant and local (n = 1), local (n = 5), or regional (n = 2). Of 51 patients with elevated preradiotherapy squamous cell carcinoma antigen levels, 33 achieved normalized levels after radiotherapy. Squamous cell carcinoma antigen normalization was associated with a higher recurrence-free survival rate at 2 years (74.3%) than that associated with nonnormalization of squamous cell carcinoma antigen (5.6%, P <.001). The extent of shrinkage ranged from 61% to 100%, and there was no local recurrence. CONCLUSION: Postradiotherapy squamous cell carcinoma antigen status is a useful indicator of clinical outcome, particularly about tumor recurrence. It is not, however, useful for assessing response to radiotherapy. Magnetic resonance imaging is useful for obtaining an objective assessment of radioresponse.
Antigens, Neoplasm↗
Microsatellite instability and immunohistochemical analysis of MLH1 and MSH2 in normal endometrium, endometrial hyperplasia and endometrial cancer from a hereditary nonpolyposis colorectal cancer patient.
Hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial cancer is associated with mutations in DNA mismatch repair genes. However, chronological changes of these genes in the endometrium have not been studied in women from HNPCC families. Tissue samples of normal endometrium, endometrial hyperplasia without atypia and endometrial cancer were collected at different times from a 41-year-old Japanese woman with a family history of HNPCC. Combined microsatellite instability (MSI) and immunohistochemical analysis of MLH1 and MSH2 predicted the presence of a mutation in MSH2 when she had endometrial hyperplasia without atypia 7 months before the diagnosis of endometrial cancer. Endometrial hyperplasia without atypia may indicate an early development of endometrial cancer in women from HNPCC families.
Adaptor Proteins, Signal Transducing↗
Ovarian tumor with functioning stroma.
The authors reported two cases with ovarian tumors with functioning stroma. One was an ovarian carcinoid with testosterone-producing stroma and another was an ovarian mucinous cystadenoma with elevated serum level of estrogen. They appeared as multilocular cystic masses with varying signal on MR. This imaging feature was mimicking both those of Sertoli-Leydig tumors with heterologous elements and granulosa cell tumors, which are well known as functioning tumors. It had been reported in pathological literatures that any type of ovarian tumors can show hormonal activity due to functional stroma, although, it is the first report in the radiological literatures.
Aged↗