Factors predicting successful discontinuation of continuous renal replacement therapy.

This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

Prognostic significance of BAF57 expression in patients with endometrial carcinoma.

This study was conducted to elucidate the prognostic significance of BAF57 in patients with endometrial carcinoma. We investigated the relationship between the immunohistochemical expression of BAF57 and various clinicopathological variables in 111 endometrial carcinomas. Both univariate and multivariate regression analyses were performed. The correlations between the BAF57 expression and the other variables including estrogen receptor (ER) and p53 were examined. The high nuclear BAF57 expression was detected in 42 (37.8%) endometrial carcinomas, and 69 (62.2%) endometrial carcinomas were defined as having low nuclear BAF57 expression. The BAF57 expression was significantly associated with the surgical stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion (LVSI) and lymph node metastasis. The 10-year overall survival rates of patients with low and high BAF57 expression were 96.9% and 58.2%, respectively (p<0.001). A multivariate analysis identified BAF57 expression as an independent prognostic factor. The BAF57 expression was significantly correlated with p53 expression (r=0.312, P=0.001), but was not correlated with ER expression (r= -0.141, P=0.14). The high BAF57 expression is an independent marker of poor prognosis of the patients in endometrial carcinomas. The inhibition of BAF57 activity may be one of the candidates for endometrial cancer therapy, especially therapy for aggressive tumors showing overexpression of p53.

Long-standing complications after treatment for cancer of the uterine cervix--clinical significance of medical examination at 5 years after treatment.

The purpose of this study is to investigate the side effect in patients who survived for more than 5 years after initial treatment for invasive cervical cancer. Between January 1984 and December 1997, 341 patients underwent primary treatment for invasive cervical cancer. One hundred nine patients who underwent medical examinations at 5 years after primary treatment were reviewed. The patients were divided into three groups: radical surgery alone (group A), radiotherapy alone (group B), and radical surgery with postoperative radiotherapy (group C). Dysuria was seen in 8%, and positive catheterized urine culture was noted in about 20% of groups A and C. Hydronephrosis was seen in 2% and 9% of groups A and B, respectively. Colitis or ulcer detected by proctosigmoidoscopy was noted in 15%, 50%, and 43% of groups A, B, and C, respectively, frequently observed in radiotherapy group (P= 0.0029). Lymphocyst was still present in 6% of group A, and leg edema was noted in 14%, 6%, and 15% of groups A, B, and C, respectively. Long-standing abnormal findings including urinary and bowel complications were presented in this study. Periodic physical examination after treatment should be performed because complications existed over a long time.

Enhancement of mitochondrial oxidative stress and up-regulation of antioxidant protein peroxiredoxin III/SP-22 in the mitochondria of human pre-eclamptic placentae.

A growing body of evidence indicates that the pathogenesis of pre-eclampsia is closely associated with oxidative stress occurring in mitochondria. In the present study, we evaluated the degree of mitochondrial lipid peroxidation by assessing the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins and examined the expression of mitochondrial antioxidant protein peroxiredoxin III/SP-22 in normal and pre-eclamptic human placentae. The accumulation of HNE-modified proteins increased to a greater extent in both the mitochondria and cytosol of pre-eclamptic placentae than in those of normal placentae. Moreover, the accumulation of HNE-modified proteins was much more evident in the mitochondria than in the cytosol, indicating that lipid peroxidation occurred mainly in the mitochondria of pre-eclamptic placentae. The mRNA expression of peroxiredoxin III/SP-22 was increased about 2-fold in pre-eclamptic placentae compared to normal placentae. The protein levels of peroxiredoxin III/SP-22 were approximately 4-fold higher in pre-eclamptic placentae than in normal placentae. Immunohistochemistry of placental tissues showed that the levels of peroxiredoxin III/SP-22 protein were increased in the trophoblasts of floating villi, stromal cells of stem villi, and decidual cells in pre-eclamptic placentae. These results indicate that peroxiredoxin III/SP-22 plays a crucial role in the protection of placental function from oxidative stress occurring in mitochondria of pre-eclamptic placentae.

Glassy cell carcinoma of the uterine cervix: combination chemotherapy with paclitaxel and carboplatin in recurrent tumor.

Combination chemotherapy with paclitaxel and carboplatin every 4 weeks for 3 cycles was administered for recurrent glassy cell carcinoma of the uterine cervix in a 67-year-old Japanese female. The response rate was 56% under computed tomography (partial response). However, the effect was transient even with follow-up radiotherapy, and further cases need to be accumulated to determine a successful treatment modality.

Enhanced protein levels of protein thiol/disulphide oxidoreductases in placentae from pre-eclamptic subjects.

Recent studies have indicated that pre-eclampsia is closely associated with oxidative stress both in maternal circulation and in the placenta. Protein thiol/disulphide oxidoreductases, such as thioredoxin, glutaredoxin, and protein disulphide isomerase have recently been found to eliminate reactive oxygen species (ROS) and regenerate oxidatively damaged proteins. Protein thiol/disulphide oxidoreductases may also play a role in combating pre-eclampsia. In this study, we examined the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins, which are markers of lipid peroxidation, in human placentae of normal and pre-eclamptic subjects. We also examined the protein levels of thioredoxin, glutaredoxin, and protein disulphide isomerase in placentae. Immunoblotting and immunohistochemistry showed that HNE-modified proteins accumulated to a greater extent in pre-eclamptic placentae than in normal placentae. In both normal and pre-eclamptic placentae, thioredoxin, glutaredoxin, and protein disulphide isomerase were detected in the trophoblasts of the floating villi. The levels of these proteins were increased approximately 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxidoreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomerase in protecting placental functions against oxidative stress caused by pre-eclampsia.

Myxoid leiomyosarcoma of the uterus. Report of a case with cytologic findings.

BACKGROUND: Myxoid leiomyosarcoma is a rare variant of uterine sarcoma, exhibiting malignant biologic behavior despite the absence of cytologic atypia and of significant mitotic activity. CASE: A 20-year-old female was referred with a cystic pelvic mass. At laparotomy, the tumor, weighed 2,200 g and originating in the left lateral uterine wall, was removed. Microscopic examination revealed well-differentiated smooth muscle cells without atypia and with a few mitotic figures in the copious myxoid matrix, suggesting myxoid leiomyosarcoma. Three years following laparotomy, an irregular mass around the uterus was noted on sonographic examination, suggesting local recurrence. Two years and six months later, the second operation was performed, and a locally recurrent, multicystic tumor weighing 3,500 g was excised. The histopathology was similar to that of the primary tumor. Cytologic findings on imprint material from the tumor revealed a few isolated or sheet like small cells consisting of spindle and polygonal cells with round and oval nuclei. Cytologic atypia was also minimal. CONCLUSION: Myxoid leiomyosarcoma should be included in the differential diagnosis of smooth muscle neoplasia.

Sarcoma botryoides of the cervix. Report of a case with cytopathologic findings.

BACKGROUND: Cytologic findings of sarcoma botryoides were still equivocal because sarcoma botryoides of the uterine cervix is an extremely rare neoplasm, and few cases have been reported to date. CASE: A 17-year-old female was diagnosed with sarcoma botryoides of the uterine cervix. The entire vaginal canal was occupied with polypoid masses, which arose from the anterior lip of the uterine cervix, and the tumor was classified as group I (Intergroup Rhabdomyosarcoma Study). After wedge resection and six courses of combination chemotherapy, the tumor recurred in the same location of the cervix as the primary lesion. Touch smear of the polypoid mass formed loose clusters and also showed short spindle cells in a necrotic background. The nucleus of the tumor cells had a thin nuclear membrane, fine chromatin pattern and partly clear nucleolus, showing mild nuclear atypia. Immunohistochemically, some of the tumor cells showed positive staining for myoglobin and desmin. CONCLUSION: The cytologic findings of sarcoma botryoides of the female genital tract are typical features of nonepithelial malignant tumor. Immunohistochemical study is useful for the diagnosis of rhabdomyosarcoma.

Localization of thioredoxin reductase and thioredoxin in normal human placenta and their protective effect against oxidative stress.

Recent studies have indicated that oxidative stress is involved in the pathogenesis of pre-eclampsia. Oxidative stress damages systemic tissues, and placental damage may result in intrauterine growth retardation and fetal distress. Thus, this study attempted to elucidate the placental localization of thioredoxin and thioredoxin reductase, substances that may reduce oxidative stress. Furthermore, it studied the defence mechanism of the thioredoxin-thioredoxin reductase system against oxidative stress in mitochondria of normal human placenta where reactive oxygen species are primarily produced. The examination of thioredoxin reductase activity in subcellular fractions of human placenta indicated that thioredoxin reductase was located not only in cytoplasm, but also in mitochondria. The existence of thioredoxin and thioredoxin reductase in human placenta was confirmed immunologically using antibodies raised against thioredoxin and thioredoxin reductase. Thioredoxin and thioredoxin reductase were localized histochemically in cytotrophoblasts, decidua, and stromal cells in the stem villi. The addition of exogenous thioredoxin and thioredoxin reductase to fumarase in mitochondria of human placenta displayed a protective effect against oxidative stress. In conclusion, this study confirmed the intracellular localization and the tissue distribution of thioredoxin and thioredoxin reductase in human placenta. Moreover, the complete thioredoxin-thioredoxin reductase system in human placenta may protect the placenta from damage caused by oxidative stress.

Clinical significance of tumor size in stage IB and II carcinoma of the uterine cervix.

The purpose of the present study was to investigate the correlation between tumor size and prognosis in stage IB and II cervical cancer and to elucidate the adequacy of new FIGO staging system for cervical cancer. The subjects included 128 patients with cervical cancer (stage IB = 86, IIA = 18, and IIB = 24) who had undergone radical hysterectomy. The largest tumor size of the pathology specimen was measured in two dimensions, and the correlation between tumor size and prognosis was investigated. In addition, tumor size of the pathology specimen was compared with the largest tumor diameter measured by MRI in stage IB cancers. Patients with a tumor size greater than 3 cm2 had a significantly worse 5-year survival rate (63%) when compared to those with tumor size no greater than 3 cm2 (96%) (P < 0.0001). Multivariate analysis revealed that independent prognostic factors were tumor size (P = 0.003) and lymph node metastasis (P = 0.015). By regression analysis, the largest tumor size of the pathology specimen was relatively well correlated with the largest tumor diameter by MRI in stage IB cancers; 3 cm2 of tumor size in the pathology specimen corresponded to 3.4 cm of tumor diameter by MRI. The adequacy of new FIGO staging system was considered relatively acceptable.

Low grade cervical intraepithelial neoplasia associated with human papillomavirus infection. Long-term follow-up.

OBJECTIVE: To investigate the correlation between the development of low grade cervical intraepithelial neoplasia (LCIN) and human papillomavirus (HPV) infection in cases with long-term follow-up. STUDY DESIGN: Forty-three cases of LCIN were followed for more than five years with cytology, colposcopy and Vira Pap. Coexistence of HPV infection was sought using a simplified HPV detection kit, the Vira Pap method (Dot Blot hybridization). RESULTS: Regressive disease was noted in 21 cases, and persistent and progressive disease was noted in 22 cases. HPV DNA was negative in 81% (17 of 21) of regressive disease and positive in 55% (12 of 22) persistent and progressive disease. LCIN had disappeared in 17 (63%) of 27 cases negative for HPV DNA and was persistent or progressive in 12 (75%) of 16 cases positive for HPV DNA. CONCLUSION: The clinical course of LCIN correlates well with HPV infection.

Cellular characteristics of Arias-Stella reaction in ectopic pregnancy. Immunocytochemical studies with epithelial membrane antigen and vimentin.

OBJECTIVE: Endometrial cytology in nine cases of ectopic pregnancy was examined in order to elucidate the cellular characteristics of the Arias-Stella reaction and decidual change. STUDY DESIGN: The cellular findings of epithelial and stromal cells were compared with histologic findings in each case. Furthermore, the immunocytochemical reactivity of each type of cell cluster-epithelial cells without atypia, epithelial cells with atypia, deep stromal cells and sheetlike stromal cells-to epithelial membrane antigen (EMA) or vimentin was investigated and compared with cytologic findings in smears stained with Papanicolaou stain. RESULTS: The distribution of each type of cell cluster correlated fairly well with the histologic findings on the endometrium. Immunocytochemical examination revealed that EMA expression coincided with cell origin identified by Papanicolaou stain. Epithelial cells with atypia, probably corresponding to the Arias-Stella reaction, frequently showed positive reactivity to antivimentin antibody as well as anti-EMA antibody. Endometrial stromal cells usually indicated negative reactivity to anti-EMA antibody. Deep stromal cells expressed vimentin, but sheetlike stromal cells, thought to be decidual cells, infrequently expressed vimentin. CONCLUSION: The Arias-Stella reaction may be the result of the regenerating and proliferating activity of endometrial glands. It is still controversial whether sheet-like stromal cells are identical to decidual cells.

Cytologic analysis of primary stomach adenocarcinoma metastatic to the uterine cervix.

OBJECTIVE: To investigate the cytologic and pathologic features of endocervical lesions in cases of gastric adenocarcinoma metastatic to the uterine cervix. STUDY DESIGN: From 1986 to 1994, four patients with gastric adenocarcinoma metastatic to the uterine cervix were treated at our department. The cervical cytologic samples were obtained by swabbing and were stained by the Papanicolaou method. Presence of tumor diathesis, number of atypical cells, cell arrangement, cytoplastic vacuoles, cellular and nuclear diameter, chromatin distribution and size of the nucleolus were investigated. RESULTS: The smear backgrounds were dirty (tumor diathesis) in two cases and clean in two. No significant difference in the number of atypical cells or in cell or nuclear diameter between primary and metastatic adenocarcinoma was shown. Cell arrangement was the different cytologic finding between primary and metastatic adenocarcinoma. Sheetlike or isolated arrangement was seen frequently in metastatic cervical adenocarcinoma. CONCLUSION: Because different cytologic features have been found in past and the present series, cytologic diagnosis of metastatic cervical adenocarcinoma should be made carefully.

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Early cervical neoplasia confirmed by conization: diagnostic accuracy of cytology, colposcopy and punch biopsy.

OBJECTIVE: To investigate the accuracy rates of cytology, colposcopy and punch biopsy in early cervical neoplasia confirmed by conization. STUDY DESIGN: During the 10 years from 1984 to 1993, cold knife conization was performed on 151 patients with early cervical neoplasia proven by punch biopsy at our department. The accuracy rates of cytology, colposcopy and punch biopsy were investigated. RESULTS: The accuracy rates of cytology, colposcopy and punch biopsy were 52% (78 of 151), 66% (100 of 151) and 66% (100 of 151), respectively. CONCLUSION: These results suggest that a composite diagnosis with cytology, colposcopy and punch biopsy is necessary for a correct evaluation. Early cervical neoplasms are frequently seen in young women, and conservative procedures, such as conization, cryosurgery and laser vaporization, are the treatments of choice in order to preserve reproductive function. We recommend conization as the best conservative procedure, with preservation of reproductive function.

Immunohistochemical distribution of surfactant apoproteins in hypoplastic lungs of nonimmunologic hydrops fetalis.

Forty-three patients with nonimmunologic hydrops fetalis (NIHF), including 32 patients (74%) with hypoplastic lung, were immunohistochemically examined for the expression of surfactant apolipoproteins (SPs), using anti-gamma G immunoglobulins against human SP-A with a molecular weight (MW) of 35 K and SP-B with a MW of 5 K compared with that in 59 patients in a control group and 45 patients with hypoplastic lung induced by causes other than NIHF. In the control group, SP-A was expressed in the lungs from 23 gestational weeks and became more numerous and intense in alveolar type II cells after 31 gestational weeks, whereas SP-B began to be expressed from 20 gestational weeks, and almost all patients showed a diffuse positivity after 26 gestational weeks. In the NIHF group, SP-A expression was generally weak, even after 31 gestation weeks. Moreover, most of the patients showing a weak expression of SP-A were also associated with hypoplastic lung and had a clinical history of persistent intrauterine pleural effusion of more than 2 weeks. Conversely, the immunoreactivity of SP-B was well preserved in NIHF cases either with or without hypoplastic lung. These results suggest that in the NIHF lung, there is a possible delay in the functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in type II cells also participates in the postnatal respiratory insufficiency in NIHF.

An immunohistochemical study of the expression of surfactant apoprotein in the hypoplastic lung of rabbit fetuses induced by oligohydramnios.

We shunted amniotic fluid from alternate gestational sacs into the maternal peritoneal cavity between 23 and 30 days gestation in fetal rabbits (full term, 31 days) to investigate the effect of oligohydramnios on surfactant apoprotein A (SP-A) expression by an immunohistochemical morphometric analysis. The amniotic shunt produced a significant decrease in the amniotic fluid volume (P < 0.02), as well as a reduction in the lung weight (P < 0.005) and lung/body weight ratio (P < 0.001), which indicated lung hypoplasia. These fetuses also showed a statistically significant reduction of SP-A expression, ie, SP-A-positive type II cells per unit area (P < 0.05), SP-A-positive type II cells/total cells ratio (P < 0.001), the percentage of SP-A-positive area per unit area (P < 0.005), and the SP-A-positive area/alveolar epithelium area plus the lung interstitium area ratio (P < 0.005). These results suggest that oligohydramnios significantly retards and modifies the structural growth and functional development of alveolar type II cells in SP-A expression. This animal model of hypoplastic lung in fetuses is thus considered to be useful in helping to further develop the treatment for hypoplastic lung.

Cytology of vulvar squamous neoplasia.

Cytologic findings on various vulvar squamous lesions are described in order to elucidate the usefulness of vulvar cytology. Lichen sclerosus, hyperplastic dystrophy and dysplasia with a few exfoliated anucleate squamous cells could not be differentiated cytologically. Numerous parakeratotic cells and dyskaryotic cells were identified in squamous cell carcinoma in situ. Three cytologic patterns were presented in cases of frankly invasive squamous cell carcinoma: negative cytology with parakeratotic cells, suspicious cytology with dyskaryotic cells and positive cytology with malignant cells. Verrucous carcinoma yielded only anucleate squamous cells. Parakeratotic cells without nuclear atypia seemed to be neoplastic cells on vulvar cytology.

[Problems in Papanicolaou classification].

There are several reasons why Papanicolaou classification should not be used for the interpretation of cytologic findings. First, many different classification criteria are sometimes used for a single pathologic condition. Second, inflammatory change or hormonal evaluation are not included in the system. Third, the classification is not compatible for the evaluation of endometrial lesions or chorionic diseases. Fourth, mismanagement of the patient is sometimes encountered when this classification is only used. Instead of Papanicolaou classification, descriptive diagnosis should be used for cytologic interpretation.