Survival benefit of pelvic and paraaortic lymphadenectomy in high-grade endometrial carcinoma: a retrospective population-based cohort analysis.

OBJECTIVE: The standard therapy for high-grade endometrial cancer is surgery but the therapeutic effects of pelvic and paraaortic lymph node dissection (LND) are poorly investigated. In this study, we retrospectively evaluated overall survival, recurrence rates and recurrence-free survival among patients with high-grade type I and II endometrial carcinoma who underwent LND. METHODS: This study included 284 patients who are recorded in the German Tumor Centre Regensburg form 1998 to 2015 and were selected by cancer grading, the absence of secondary tumors, primary surgery including hysterectomy and available follow-up. 244 of the 284 patients in this cohort were unequivocally classified as R0 after resection. RESULTS: A significantly increased overall survival was observed for systematic LND of 25 or more paraaortic and pelvic lymph nodes versus patients who did not undergo such intervention (p < 0.001) or had elective LND of 1-24 lymph nodes both in univariable (p = 0.016) and multivariable (p = 0.014) analysis. A similar observation was made for recurrence-free survival of patients in the cohort who underwent complete tumor resection (R0). In addition, a reduced cumulative recurrence rate was observed for patients with systematic LND. CONCLUSIONS: Our study provides evidence that the systematic removal of 25 or more pelvic and paraaortic lymph nodes reduces the recurrence rate and that it is beneficial for the long-term overall and recurrence-free survival of patients with high-grade endometrial cancer.

Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays.

AIM: To investigate whether protein expression or cellular localisation of P-cadherin is associated with clinicopathological characteristics in benign and malignant melanocytic skin tumours. EXPERIMENTAL DESIGN: P-cadherin expression and the Ki-67 labelling index were analysed immunohistochemically by using tissue microarrays (TMAs). Membranous and cytoplasmic expression was scored semiquantitatively (0 to 2+). RESULTS: P-cadherin protein expression of any intensity (1+ to 2+) was detected in the membrane in 41.5% (132/318) and in the cytoplasm in 64.2% (204/318) of patients. In general, P-cadherin expression was significantly reduced in malignant melanomas (p<0.001) and melanoma metastases (p<0.001), compared with benign nevi. Additionally, loss of membranous P-cadherin was associated with Clark level (p = 0.011) and tumour thickness (p<0.001). Interestingly, a significantly lower P-cadherin expression was shown by dermal nevi than by compound and junctional nevi (p = 0.005; p = 0.025). In primary melanomas, a Ki-67 labelling index <5% was not associated with P-cadherin protein expression, suggesting that loss of P-cadherin expression was not associated with proliferation. None of the other clinical and histological factors analysed was significantly related to P-cadherin expression. Low cytoplasmic P-cadherin expression was associated with tumour recurrence (p = 0.03) in all the patients who were analysed. After testing various multivariate Cox regression models, loss of cytoplasmic P-cadherin expression remained a highly significant adverse risk factor for tumour recurrence in patients with tumours <2 mm. CONCLUSIONS: Loss of cytoplasmic P-cadherin expression is common in advanced melanomas and can be a prognostic marker of progression in patients with melanoma, most useful in patients with primary tumours <2 mm in thickness.

[Measurement of corneal thickness in glaucoma patients]. / Hornhautdickenmessung bei Glaukompatienten.

BACKGROUND: For the past 5 decades, Goldmann's applanation tonometry has been the basis for measurement of intraocular pressure. In this process, it is assumed that the corneal architecture-and particularly corneal thickness-does not have significant influence on the applanation tonometry. The aim of this study was to assess central corneal thickness in patients with primary open angle glaucoma (POWG), normal tension glaucoma (NDG), and ocular hypertension (OHT) compared to the central corneal thickness of control subjects. METHOD: In 200 consecutive glaucoma patients corneal pachymetry was performed with the Orbscan II system and a pachymetry map was obtained. Simultaneously, corneal pachymetry was also performed in 200 age- and sex-matched control subjects. To avoid diurnal variations the pachymetry measurements were performed at the same time of the day. RESULTS: The central corneal thickness (CCT) distribution turned out to be a near-Gaussian curve in patients with glaucoma and in the control subjects. The mean CCT in glaucoma patients was 561+/-49.4 micro m with a minimum of 448 micro m and a maximum of 732 micro m. In control subjects the mean CCT was 555.9+/-34.6 micro m with a minimum of 480 micro m and a maximum of 635 micro m. Further evaluation of CCT of glaucoma patients demonstrated that the CCT in patients with POWG was 559.5+/-43.5 micro m, in patients with NDG was 530.3+/-51.1 micro m and with OHT was 624.2+/-25.4 micro m. CONCLUSIONS: Central corneal thickness in patients with OHT was significantly greater, and in patients with NDG significantly lower, compared to control subjects. In defining the desired intraocular pressure in glaucoma patients, in the future CCT measurements should be considered along with intraocular pressure measurement and visual field analysis.

Tissue-specific expression of human lipoprotein lipase. Effect of the 3'-untranslated region on translation.

Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3'-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA form. To determine whether there was any functional significance to this tissue-specific mRNA expression, poly(A)-enriched RNA from adipose tissue and muscle were translated in vitro, and the poly(A)-enriched RNA from muscle was more efficiently translated into LPL protein. The increased translatability of the 3.6-kb form was also demonstrated by cloning the full-length 3.2- and 3.6-kb LPL cDNA forms, followed by in vitro translation of in vitro prepared transcripts. To confirm that this increased efficiency of translation occurred in vivo, Chinese hamster ovary cells were transfected with the 3.2- and 3.6-kb LPL cDNAs. Cells transfected with the 3.6-kb construct demonstrated increased LPL activity and synthesis, despite no increase in levels of LPL mRNA. Thus, human muscle expresses the 3.6-kb form of LPL due to a non-random choice of polyadenylation signals, and this form is more efficiently translated than the 3.2-kb form.

Expression of lipoprotein lipase in rat muscle: regulation by feeding and hypothyroidism.

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is found predominantly in adipose tissue and muscle. We examined the mechanism of regulation of LPL in muscles composed of different fiber types (soleus, extensor digitorum longus, and heart) in fed, fasted, and hypothyroid rats. In all muscles, the detergent-extractable (EXT) fraction represented approximately 95% of total LPL activity and mass. LPL activity was similar in the heparin-releasable (HR) fractions of heart and soleus (predominantly type I fibers), while in the EXT fraction LPL activity in soleus was 418 +/- 48 nEq/min per g, and in heart was 272 +/- 30 nEq/min per g (P < 0.05). However, LPL activity in extensor digitorum longus (EDL, predominantly type II fibers) was considerably lower (7.9 +/- 0.8 nEq/min per g in EXT, P < 0.0001 versus heart and soleus). LPL immunoreactive mass followed a pattern similar to LPL activity. LPL mRNA levels were quantitated by both Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), and were approximately equal in heart and soleus, and 5-fold lower in EDL. In response to feeding, LPL activity, mass, and mRNA levels in heart were 30% to 50% lower than in fasted rat heart, although feeding had no effect on soleus or EDL. In hypothyroid animals, muscle LPL activity was increased by 3- to 4-fold in the HR (but not EXT) fractions of heart and soleus (P < 0.05), with no change in LPL mass or mRNA. Thus, muscles with oxidative, type I fibers expressed higher levels of LPL mRNA than muscles containing glycolytic, type II fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echocardiographic contractility reserve and invasive hemodynamics in physical stress in probands with healthy hearts and patients with dilated cardiomyopathy]. / Echokardiographische Kontraktilitätsreserve und invasive Hämodynamik unter körperlicher Belastung bei Herzgesunden und Patienten mit dilatativer Kardiomyopathie.

In the present study, 17 patients with angiographically proven dilative cardiomyopathy (CM) were investigated simultaneously by both invasive right heart catheter and 1D/2D echocardiography at rest (R) and during bicycle exercise (E) stress test. They were compared with 14 normal subjects (N). The echocardiographic contractility reserve was determined as an increase in the systolic pump function (shortening fraction-SF, ejection fraction - EF) and compared with pulmonary capillary wedge pressure during exercise. 14/17 echocardiograms of dilative cardiomyopathy and all echocardiograms of normal subjects at rest as well as during exercise could be accepted. In N, echocardiographic parameters of systolic function significantly increased during exercise, whereas dilative cardiomyopathy showed decreased contractility reserve with no increase in pump function (for CM patients, at rest SF: 21.3% +/- 8%; EF: 41.6% +/- 14%; exercise SF: 21.3 +/- 9%; EF: 40.7% +/- 15%). Hemodynamic investigation in CM showed no increase in stroke volume accompanied by a pathologic increase in pulmonary wedge pressure, ranging from x = 16.4 mmHg at rest, up to 30.0 mm Hg in exercise (p less than 0.001), whereas in normal subjects, no pathologic increase in pressure was present (from 10.3 mm Hg at rest to 13.7 mm Hg during exercise). There were closed relations between invasive and non-invasive data. The relative alteration of stroke volume during E showed in N and in CM good correlation with echocardiography (N + 19%, CM -2%) and invasive data (N + 18%, CM + 2%). FSe during stress and PCPm showed a closed inverse correlation during exercise (p less than 0.001; r = 0.8). The lower the contractility in echocardiogram, the higher PCPm was in exercise.