Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Diagnostic Accuracy of Liquid Biopsy in Endometrial Cancer.

BACKGROUND: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. METHODS: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. RESULTS: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. CONCLUSIONS: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted.

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics.

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available.

The Prognostic Significance of Eukaryotic Translation Initiation Factors (eIFs) in Endometrial Cancer.

Whilst the role of eukaryotic translation initiation factors (eIFs) has already been investigated in several human cancers, their role in endometrial cancer (EC) is relatively unknown. In the present retrospective study, 279 patients with EC (1180 samples) were included (mean age: 63.0 years, mean follow-up: 6.1 years). Samples were analysed for expression of 7 eIFs subunits (eIF2α, eIF3c, eIF3h, eIF4e, eIF4g, eIF5, eIF6) through immunohistochemistry and western blotting. Fifteen samples of healthy endometrium served as controls. Density and intensity were assessed and mean combined scores (CS) calculated for each patient. Upon immunohistochemistry, median eIF5 CS were significantly higher in EC as compared with non-neoplastic tissue (NNT, p < 0.001), whilst median eIF6 CS were significantly lower in EC (p < 0.001). Moreover, eIF5 (p = 0.002), eIF6 (p = 0.032) and eIF4g CS (p = 0.014) were significantly different when comparing NNT with EC grading types. Median eIF4g CS was higher in type II EC (p = 0.034). Upon western blot analysis, eIF4g (p < 0.001), peIF2α (p < 0.001) and eIF3h (p < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (p < 0.001). The remaining eIFs were non-significant. Besides tumour stage (p < 0.001) and patient's age (p < 0.001), high eIF4g CS-levels were independently associated with poor prognosis (HR: 1.604, 95%CI: 1.037-2.483, p = 0.034). The other eIFs had no prognostic significance. Notably, the independent prognostic significance of eIF4g was lost when adding tumour type. Considering the difficulties in differentiating EC type I and II, eIF4g may serve as a novel prognostic marker indicating patient outcome.

HOTAIR in relation to epithelial-mesenchymal transition and cancer stem cells in molecular subtypes of endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)-mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers. METHODS: The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes - SNAIL and SLUG - and the CSCs marker CD133. RESULTS: Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes. CONCLUSIONS: Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.

Immunohistochemical characterisation of molecular subtypes in endometrial cancer.

Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy.

[Endometrial cancer in young women--clinical and molecular aspects]. / Rak blony sluzowej trzonu macicy u mlodych kobiet--aspekty kliniczne i molekularne.

OBJECTIVES: The aim the study was to compare two groups of endometrial cancer patients (below and above 45 years of age) in the aspect of clinicopathological and molecular data. MATERIAL AND METHODS: The study encompassed 456 primary tumour samples retrospectively collected from a cohort of endometrial cancer patients, primarily treated by surgery Molecular analysis covered: copy number variations of 10 genes (TOP2A, ERBB1, ERBB2, ERBB3, ERBB4, MYC, CCND1, ESR1, PIK3CA, RAD21) analyzed by quantitative PCR; mRNA expression of 6 genes (SCGB2A2, RAD27, RUNX1, SNAI1, SNAI2, PROM1) analyzed with the use of reverse transcription quantitative PCR; protein expression analysis of 8 markers (PGR, ESR1; ERBB1, ERBB2, ERBB3, ERBB4, TOP2A, pAKT1) performed with the use of immunohistochemistry. RESULTS: The younger group of patients was characterized by less frequent hypertension (p <0.00007), less frequent myometrial infiltration (p=0.002) and longer overall survival (p=0.003). Apart from RAD21 gene aberrations, which were more frequent in younger patients (p=0.02), the study revealed no statistically significant differences between the groups. CONCLUSIONS: The study showed no molecular differences in the profile of younger and older endometrial cancer patients. Data on both the prognostic and predictive significance of RAD21 in endometrial cancer are still insufficient. The clinical profile of younger patients with endometrial carcinoma was slightly better when compared to elderly patients. Younger patients were characterized by longer overall survival.

HER2-positive endometrial cancer subtype carries poor prognosis.

Endometrial cancer (EC) is a hormone-dependent, most frequent malignancy of the female genital tract, yet no molecular subtype classification based receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) has been established so far. Assuming that molecular subtypes might differ fundamentally in EC, we analyzed expression levels of ER, PR, and HER2 with immunohistochemistry and aimed to determine clinical significance of four molecular subtypes: ER+/PR+/HER2+; ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2-. The study included 400 formalin-fixed paraffin-embedded primary tumor EC samples which covered all stages of endometrial carcinoma, from IA to IVB. ER-/PR-/HER2+ subtype correlated with the poorest outcome, ER+/PR+/HER2- subtype was associated with the most favorable prognosis (p = 0.002). Molecular subtype division remained an independent prognostic factor in multivariate analysis, accompanying parameters such as diabetes, hypertension, stage, myometrial infiltration, and metastases, all of which yielded hazard ratios between 1.39 and 2.23. ER+/PR+/HER2+ and ER+/PR+/HER2- subtypes had low average TP53 and TOP2A expression levels when compared with ER-/PR-/HER2+ and ER-/PR-/HER2- (both p < 0.00001). Molecular subtypes in EC do show diversity in terms of prognosis, clinicopathological, and molecular characteristics. ER-/PR-/HER2+ subtype exhibit is exceptionally aggressive tumor characteristics. Subtype differentiation might aid prediction of treatment response in EC.

Tumor heterogeneity at protein level as an independent prognostic factor in endometrial cancer.

Intratumor heterogeneity implies heterogeneous protein function, facilitating tumor adaptation which results in therapeutic failure. We hypothesized that tumor heterogeneity at protein level may influence the course of the disease. As a single biopsy might not represent the full biologic complexity of the tumor, we have analyzed immunohistochemically four different cores obtained from each primary tumor within the cohort of 364 patients with endometrial cancer (EC). The following proteins were examined: estrogen receptor 1 (ESR1), progesterone receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%) patients were classified as "globally heterogeneous". Cumulative tumor heterogeneity strongly correlated with the presence of metastases, higher stage, and higher grade of the disease (all P b .05). It also carried negative prognostic value (P=.0008). We show that the degree of heterogeneity in EC might serve as a clinically valid molecular marker.

A multimarker qPCR platform for the characterisation of endometrial cancer.

The molecular background of endometrial cancer (EC) has not been fully elucidated. In the present study, we developed a quantitative PCR (qPCR) platform to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1-4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from 157 EC patients (stage I-IV) to verify its clinical utility and to examine the diagnostic and prognostic significance of the analysed biomarkers. The gene dosage pattern of the ERBB family and its downstream effectors PI3K and MYC showed particularly strong correlations with clinicopathological data. The ERBB PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02). The implemented hierarchical clustering revealed that cluster 2 was characterised by high copy numbers of the studied genes. Cluster 2 was associated with shorter overall survival (p=0.05). The platform was found to be a fast and simple method for direct analysis of the genes involved in uterine carcinogenesis, making it feasible for EC biology characterisation.

Epithelial-mesenchymal transition and cancer stem cells in endometrial cancer.

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are presumed to be key conditions for malignancy. Data concerning their role in endometrial cancer (EC) are scarce. We aimed to investigate the possible link between EMT and CSCs markers in EC samples. MATERIALS AND METHODS: The study encompassed 156 primary tumour samples. Using RT-qPCR, we analyzed the expression of EMT-related genes, SNAIL and SLUG, and the CSCs marker CD133. RESULTS: SNAIL and SLUG correlated with each other (R=0.33; p=0.00003). All the studied genes were expressed in both normal and malignant endometrial tissue. Decreased SNAIL expression was found to correlate with post-menopausal status (p=0.002). Decreased SLUG expression was associated with shorter overall survival (p=0.01). CONCLUSION: SLUG expression could serve as a prognostic factor in EC. No correlation between the expression of EMT and CSCs markers was found, suggesting there to be no association between the EMT and CSC phenotype in endometrial cancer.

Comparison of SPECT-CT results and intraoperative detection of sentinel lymph nodes in endometrial cancer.

OBJECTIVES: The aim of the study was to compare the results of single-photon emission computed tomography-computed tomography (SPECT-CT) with those of intraoperative gamma probe detection and assess the clinical utility of SPECT-CT for sentinel lymph node biopsy in endometrial cancer. MATERIALS AND METHODS: We investigated 70 patients with endometrial cancer who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy (routine pelvic and para-aortic lymphadenectomy was additionally performed in high-risk patients). Tc-99m radiocolloid albumin was injected into the cervix and a blue dye was injected superficially into the fundus. RESULTS: SPECT-CT revealed hot spots in 64 patients (91.4%). The detection rates were 97.1 and 94.3% using the combined technique and the hand-held gamma probe, respectively. In 19 cases (27.1%) 35 hot spots detected on SPECT-CT were not diagnosed as sentinel lymph nodes (SLNs) during surgery. In each patient with undetected hot spots located in the common iliac or para-aortic regions, hot SLNs were found during surgery in the obturator or external iliac region. In addition, SPECT-CT had detected 88.9% of the SLNs found during surgery. With respect to the 13 cases not detected on SPECT-CT, the hot SLNs had very low activity. Using the combined method, 95.1% of SLNs were found in typical locations (external iliac or obturator nodes). There were two metastatic nodes: one in SLN and one in nonsentinel node. CONCLUSION: SPECT-CT yields a high SLN detection rate; however, there is significant discrepancy in comparison with intraoperative findings, which limits its clinical utility. In addition, in the majority of cases SLNs are found in typical areas, which means that they can be reliably detected using an intraoperative gamma probe.

Deregulation of RAD21 and RUNX1 expression in endometrial cancer.

Cohesins and cohesin-regulated genes are deregulated in numerous types of human cancer. However, data concerning their status and role in endometrial cancer are scarce. This study aimed to determine the clinical significance of double-strand-break repair protein rad21 homolog (RAD21) and runt-related transcription factor 1 (RUNX1) gene dosage and mRNA expression in endometrial cancer. RAD21 is a component of the cohesin complex, crucial for chromosome segregation and DNA repair. RUNX1 is the transcription factor implicated in RAD21 regulation. The study group included 144 endometrial cancer patients. RAD21 and RUNX1 expression profiles were measured by reverse-transcription quantitative PCR. RAD21 gene dosage was determined by quantitative PCR. RAD21 gene dosage was associated with RAD21 mRNA expression (ϱ=0.22; p=0.009). Furthermore, RAD21 expression strongly correlated with RUNX1 expression (ϱ=0.43; p<0.0000001). Increased RAD21 gene dosage correlated with more advanced tumor stage (p=0.021), higher grade (p=0.021), cervical involvement (p=0.01) and the absence of obesity (p=0.025), while RAD21 mRNA expression correlatd with cervical involvement (p=0.027). The mRNA expression of RAD21 and RUNX1 was found to be deregulated and co-dependent in endometrial cancer. RAD21 gene dosage is associated with unfavorable tumor characteristics. However, elucidating the role of these molecular markers in endometrial oncogenesis requires further investigation, including functional studies and survival analysis.

Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer.

The HtrA family of serine proteases takes part in cellular stress response including heat shock, inflammation and cancer. Downregulation of human HtrA1 and HtrA3 genes has been reported in some cancers, including endometrial cancer (EC), suggesting a tumor-suppressor role for both genes. The mechanism of the HtrA function is not known, however, evidence exists showing that both HtrA1 and HtrA3 regulate biological processes by modulating TGF-beta signaling. In the presented study the expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes was examined in 124 endometrial tissue specimens including 88 cancers and 36 normal endometria. The expression of the tested genes was evaluated at mRNA and protein levels by semi-quantitative RT-PCR and western blotting methods, respectively. Our results showed significant decrease of HtrA1 and HtrA3 mRNA and protein levels in EC compared to normal tissues. The most dramatic decrease was found for HtrA3 at both mRNA and protein levels (3.2- and 5.6-fold, respectively). Moreover, the HtrA3 protein (short isoform) was not detected in 19% of the cancers, and its level decreased from the premenopausal to the postmenopausal group. The HtrA2 protein levels were significantly lower in EC tissues compared to normal tissues. We also found a significant increase of the TGF-beta1 protein level in EC as well as a significant negative correlation between HtrA1/2/3 and TGF-beta1 relative protein levels. Our results showing downregulation of HtrA1 and HtrA3 gene expression support previous studies suggesting a tumor suppressor role for these genes. Furthermore, our data suggest that HtrA2 may be involved in EC development as well as suggest the involvement of HtrA1, HtrA2 and HtrA3 in the inhibition of TGF-beta signaling in endometrial tissues.

[Recurrence of endometrial cancer after surgical treatment]. / Ryzyko wznowy procesu nowotworowego wsród chorych na raka blony sluzowej trzonu macicy.

OBJECTIVES: The purpose of the research was to analyze the frequency and location of endometrial cancer recurrence in a group of women who underwent surgery due to neoplasm and frequency of relaparotomy because of the neoplasm recurrence. MATERIALS AND METHODS: 292 women underwent operation in Dept. of Gynecology at Medical University of Gdansk due to endometrial cancer in clinical stage IA-IV by FIGO 1988 in the years of 1981-1996. All materials were analyzed using Microsoft Excel 97. The information was gathered from the following sources: case histories Dept.of Gynecology and Dept. of Oncology and Radiotherapy Medical University of Gdansk, case histories from Dept.of Radiotherapy Marine Hospital in Gdynia-Redlowo and questionnaires sent to patients. RESULTS: The mentioned above group of 292 women underwent surgery. As far as 233 instances (79.8%) are concerned, only hysterectomy with bilateral oophorectomy was used, in 23 situations (7.9%)--also the lymph nodes biopsy was performed whereas in 10 cases (3.4%)--appendectomy and/or omentectomy. 24 women (8.2%) underwent Wertheim-Meigs operation and only 2 patients (0.7%)--with vaginal hysterectomy. 138 women were chosen to take part in the next stage of treatment. The regression of neoplasm illness was discovered among 13 patients (4.5%) with the apex of vagina being the most common place. The result comprised of 6 women--46.1% of all recurrences. All regressions happened 1-2 years after surgery. 5-year-survival for patients with regression was 23.1% which is 3 women. Relaparotomy due to neoplasm illness took part in 9 situations (3.1%). The danger of fatality grew up to 16 month after first surgical treatment; after this period of time the risk of dying went down. CONCLUSIONS: The recurrence of endometrial cancer can be observed among small group of patients (4.5%). When we concentrate the patients with regression of neoplasm disease, we can observe a high rate of fatality.

[Fertility of women after conservative operation for borderline ovarian tumors]. / Analiza plodnosci kobiet po leczeniu oszczedzajacym z powodu nowotworów jajnika o granicznej zlosliwosci.

OBJECTIVES: The aim of the study was to assess procreation in group of patients who were treated by conservative operation for borderline tumors of the ovary. DESIGN: The analysis included 42 patients conservatively operated for ovarian tumor of borderline malignancy in Department of Gynecology Medical University of Gdansk between 1978-2000. The incidence of pregnancy, age of patients, tumor pathology, type of conservative surgery and the course of pregnancy and labour were evaluated in this study. RESULTS: In the analysis group were 36 (85.7%) stage IA, 2 (4.8%) stage IB, 3 (7.1%) stage IC and 1 (2.4%) stage III C patients. Unilateral adnexectomy was performed in 36 (85.7%) patients, 4 (9.5%) unilateral cystectomy, 2 (4.8%) bilateral cystectomy with omentectomy in one case. After conservative operation 10 (23.8%) patients were pregnant and delivered healthy children but 2 patients delivered twice and 1 third. Recurrence was observed in 2 patients in period of 27 and 50 months after operation. 5 years survival was 97.6%. CONCLUSIONS: Percentage of pregnancy after conservative treatment for borderline ovarian tumors was high (23,8%) and number of recurrences was low so conservative surgery allows young women to retain procreational potential without increasing risk of recurrence.

[Rare tumours--are they really rare in the Polish children population?]. / Nowotwory rzadkie--czy rzeczywiscie rzadkie w populacji polskich dzieci?

Clear statement that pediatric neoplasms are really rare is not easy. Thus the incidence of rare tumours in children has not been defined so far. The paper efforts to assess the topic of rare tumours of childhood in the Polish population. Following two categories are proposed: tumours typical for adults, but possible in children (neoplasms of epithelial origin--mainly carcinomas, melanomas, carcinoids) and paediatric tumours consisting less than 10% of cases in corresponding clinical groups according to the ICCC classification. Data on 317 patients aged 0-18 years treated in centres associated in the Polish Paediatric Group for Solid Tumours (PPGST) were analysed. Classical adult malignancies were registered in 130 patients: carcinomas in 90 (mean age 12.6 +/- 4.5 years), melanomas in 25 (mean age 9.4 +/- 4.9) and carcinoids in 9 (mean age 14.5 +/- 1.2 years). Non epithelial neoplasms were registered in 187 patients (mean age 10.4 +/- 5.5). That group included rare tumours of soft tissue, CNS, bones and other organs. Treatments of certain groups were specified by separate therapeutic protocols within PPGST. Rare malignancies of adult-type among children under 18 years of age in Poland comprised 1.5% of all pediatric neoplasms. The incidence of adult-type neoplasms increased with age until 14 years. In patients over 15 years of age the number of registered cases decreased. It may suggest a first peak of incidence in early adolescence or an underestimation of number of patients with carcinoma aged over 15 years. In the analyzed group, the mean age of patients with carcinomas and other epithelial and unspecified tumours significantly exceeded the age of children with rare neoplasms of non-epithelial origin (12.1 +/- 4.7 vs 10.4 +/- 5.5 years; p<0.05). A very young age at diagnosis of malignant melanomas (mean 9.4 years) and numerous cases of carcinomas affecting the digestive tract (n=24; 27% of all carcinomas), especially those located in colorectal region (n=10), seem surprising. The preliminary analysis of the collected data on rare neoplasms in Poland encourage to undertake a prospective study, meant to link the epidemiology and characteristics of rare epithelial tumours in childhood with diagnostic and therapeutic suggestions for these types that are not coordinated within Polish Paediatric Group of Solid Tumours.

[Obesity, hypertension and diabetes mellitus in patients with endometrial cancer]]. / Otylosc, nadcisnienie tetnicze i cukrzyca a rak blony sluzowej trzonu maoicy.

OBJECTIVES: The aim of the study was to determinate the frequency of obesity, hypertension and diabetes mellitus and its potential influence on clinical stage of endometrial cancer in a large, representative group of 292 patients operated because of endometrial cancer. MATERIALS AND METHODS: The group of 292 women operated because of endometrial cancer in clinical stage IA-IV between 1981-1996 in 2nd. Dept. of Obstetrics and Gynecology Medical University of Gdansk was analysed. The frequency of obesity, hypertension and diabetes mellitus in analysed group and interval between the beginning of internal diseases and the beginning of neoplasmatic disease was detected. The potential influence of obesity, hypertension and diabetes mellitus on clinical stage of endometrial cancer was analysed, too. RESULTS: The subgroup of patients with obesity, hypertension and diabetes mellitus was 54.1% of all treated women (158 patients). Only 47 women (19.5%) have normal Body Mass Index. The most often patients with abnormal weight (30.7%), obesity (36.1%) and pathologic obesity (12.4%) were found. 114 women (39.0%) were treated because of hypertension and 41 women (14.0%)--because of diabetes mellitus. Long-time hypertension and diabetes mellitus before the treatment because of endometrial cancer in analysed group were found. No influence of obesity, hypertension and diabetes mellitus on clinical stage of endometrial cancer was detected. CONCLUSIONS: Long-time hypertension and diabetes mellitus before the treatment because of endometrial cancer in analysed group was found. No influence of obesity, hypertension and diabetes mellitus on clinical stage of endometrial cancer was detected.

[A case of rupture of myomatous uterus in the course of delivery]. / Sródporodowe pekniecie miesniakowatej macicy--opis przypadku.

THE AIM OF THE STUDY: A case of rupture of myomatous uterus during term delivery was described. 38-years old women delivered in 41 Hbd of fourth pregnancy. She was after two normal deliveries and one abortion. A 15 cm myoma of uterus was examined during pregnancy. In a course of pregnancy and delivery no abnormalities was detected. The first period of delivery took 2 hours 15 min., the second--30 min. The newborn was fine (Apgar 7, 4180 g, 56 cm). Just after the delivery a huge haemorrhage took place, which lasted in spite of medicines, two abrasions and tampooning of the uterus. The women lost over 2000 ml of the blood and symptoms of haemorrhage shock took place. During laparotomy a cupped uterus with large myoma and complete rupture of the uterus under the myoma was find. A hysterectomy and adnexectomy was performed. 13 days after laparotomy the patient was fine and went home. Histologically a "Ruptura recens parietis colli uteri loco leiomyomata immaturo typi bizzare in utero post partum" was find.