Isolated gestational proteinuria preceding the diagnosis of preeclampsia - an observational study.

INTRODUCTION: Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. MATERIAL AND METHODS: This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. RESULTS: IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2-18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. CONCLUSIONS: IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.

Urinary protein-to-creatinine ratio in pregnant women after dipstick testing: prospective observational study.

BACKGROUND: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein-to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. METHODS: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. RESULTS: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and ≥ 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 + . CONCLUSIONS: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with ≥ 1+ as well as normotensive women with ≥ 2+ on dipstick test should be advised to undergo the P/Cr test.

Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta.

OBJECTIVE: Local invasion is a common pattern of spread in uterine cervical squamous cell carcinoma (CSCC). Although transforming growth factor-beta (TGF-ß) facilitates invasion of various types of cancer cells, the role of the TGF-ß pathway in CSCC is unclear. In this study, we analyzed the role of TGF-ß signaling in the progression of CSCC. METHODS: Immunohistochemistry was used to examine the expression of TGF-ß pathway molecules in 67 CSCC samples with clinicopathological data. Activation of the TGF-ß pathway was investigated following co-culture of CSCC cells and cervical cancer-associated fibroblasts (CCAFs). RESULTS: Clinicopathological analysis of CSCC samples revealed that prominent expression of TGF-ß receptor-2 was more frequent in CSCC with lymphovascular space invasion (LVSI) than without LVSI (p < 0.01). Lymph node metastasis was more frequent in cases in which phosphorylated SMAD3 (pSMAD3) was localized exclusively at the boundary of tumor clusters (n = 9, p < 0.05). Recombinant TGF-ß1 increased pSMAD3 expression and enhanced cellular invasion (p < 0.005) in CSCC cells, which was attenuated by an inhibitor of the TGF-ß receptor (p < 0.005). Enhanced pSMAD3 expression and invasion was also observed when conditioned media from CSCC cells co-cultured with CCAFs were administered. Luciferase assays showed that this medium contained a large amount of active TGF-ß. Along with TGF-ß activation, thrombospondin-1 was upregulated in both CSCC cells and CCAFs, while thrombospondin-1 silencing in either CSCC cells or CCAFs repressed the activity of TGF-ß. Thrombospondin-1 was prominently expressed in cases with pSMAD3 boundary staining (p < 0.05). CONCLUSIONS: These results suggest that interaction between CSCC cells and surrounding CCAFs activates TGF-ß via thrombospondin-1 secretion to facilitate CSCC invasion.

Clinical approaches to treating papillary squamous cell carcinoma of the uterine cervix.

BACKGROUND: Papillary squamous cell carcinoma (PSCC) of the uterine cervix is difficult to diagnose due to its rarity and limited data regarding its clinical behavior. We attempted to assess the degree of stromal invasion using magnetic resonance imaging (MRI) and evaluate possible treatments for this lesion in view of its clinical behavior. METHODS: We analyzed 28 cases of PSCC diagnosed on the colposcopic selective biopsies. We studied the rate of accuracy of diagnoses of the colposcopic selective biopsies compared with the final diagnoses, and compared the rate of stromal invasion between the MRI and pathological findings while focusing on surgical methods and the clinical prognosis. RESULTS: Of the 28 patients, only 12 exhibited true PSCC. The other 16 patients were ultimately diagnosed with SCC or adenosquamous carcinoma based on the finding of the surgical specimens and exhibited relatively poor prognoses. Among the 12 true PSCC cases, the rate of diagnostic accuracy of stromal invasion (with or without) was only 58% (7/12) on the colposcopic selective biopsies. However, we were able to predict the presence of stromal invasion (microscopic borderline: approximately 3 mm) before surgery using MRI. None of the 10 patients treated with radical surgery displayed lymph node metastases. In addition, all 12 study patients exhibited no recurrence (mean: 49 months) and survived. CONCLUSIONS: MRI can be used to detect preinvasive and microinvasive disease before surgery. It is possible to select a less invasive surgical method than radical surgery in cases of preinvasive and microinvasive PSCC in view of the indolent clinical behavior of this disease.

Carbonic anhydrase type IX expression in lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervix.

The significance of carbonic anhydrase (CA-IX) expression in endocervical glandular lesions was determined to assess the utility of CA-IX immunohistochemistry for the identification of gastric-type endocervical adenocarcinoma and its related lesions. In this study, lobular endocervical glandular hyperplasia (LEGH) (n=5), atypical LEGH (ALEGH) (n=6), and endocervical adenocarcinomas, including usual-type (UEA) (n=6) and gastric-type (GAS) (n=7), were examined by immunohistochemistry for CA-IX expression. The proportion of positive staining and intensity was evaluated as between 0 and 3+. All 13 UEAs and GASs were positive for CA-IX, with 9 cases showing 3+ staining, and 8 cases showing positive areas exceeding 50%. All 11 LEGHs were positive for CA-IX, with all cases showing 50% or more positive areas, although only one case was 3+ positive. Five of 6 ALEGHs were positive for CA-IX, with 4 cases showing 3+ positivity in 100% of the lesion. Non-neoplastic glands were negative for CA-IX, although reserve cell populations and tubal metaplasias were positive for CA-IX. Although CA-IX appears to be involved in tumor progression and may be diagnostically useful in cases of endocervical adenocarcinoma and its precursors, LEGH can be a pitfall, and staining results should be combined with morphology.

Pathways of metastases from primary organs to the ovaries.

To investigate the metastatic pathways from the primary organs to the ovaries, we examined the microscopic findings from 18 original and 18 metastatic ovarian tumors carefully. In addition, we examined the immunohistochemical findings (Victoria blue stain for vascular invasion and D2-40 expression for lymphangio invasion) of metastatic ovarian tumors carefully. There were 4 (57%) ovarian lymphangio invasion cases in the 7 gastric cancers, but there were no cases in the 6 colorectal cancers (P < 0.05). There were 4 (67%) ovarian vascular invasion cases and one (17%) liver metastasis case in the 6 colorectal cancers, while there were no ovarian vascular invasions (P < 0.05) or no liver metastases in the 7 gastric cancers. The patients with metastatic ovarian tumors originating from distant organs who were treated at the same time as the original cancers had a significantly poorer prognosis than the patients with ovarian tumors treated later (P < 0.05). The rate of lymphatic metastasis from the stomach to the ovary was significantly higher than from the colon to the ovary. In addition we hypothesized that the rate of intravascular metastasis from the colorectum to the ovary was relatively higher than from the stomach to the ovary.

Retroperitoneal lipoma arising from the urinary bladder.

Retroperitoneal benign lipomas are extremely rare and represent about 2.9% of all primary retroperitoneal tumors. About 80% of the tumors in the retroperitoneal cavities are malignant neoplasms. We experienced a case of a retroperitoneal lipoma simulating an ovarian mature cystic teratoma. A diagnosis was correctly made by magnetic resonance imaging (MRI) prior to surgery, and a total tumorectomy was performed. The retroperitoneal lipoma was recognized to have arisen from the urinary bladder. Histological sections revealed a tumor consisting of typical adipose cells without atypia. These types of lipomas should be carefully followed-up because they often recur and undergo malignant transformations.