Discrepancy between recommendations regarding hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer management: a narrative review.

BACKGROUND AND OBJECTIVE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversial in ovarian cancer (OC) management. Doubts are related mainly to HIPEC effectiveness, but also to its safety. European Society of Medical Oncology and European Society of Gynecologic Oncology do not consider HIPEC as a standard of care. Opposite to European recommendations, National Comprehensive Cancer Network found HIPEC as a treatment option in patients undergoing interval debulking surgery in first-line treatment. This may be confusing for oncologists in clinical practice. The aim of this narrative review is to present literature review focusing on efficacy, confounding factors, complications and immunological issue of HIPEC in OC management. METHODS: PubMed was searched for meta-analyses, randomized trials, observational studies, experimental studies to outline the role of HIPEC in OC management since January 2015 until August 2023. Keywords included "hyperthermic intraperitoneal chemotherapy", "HIPEC", "ovarian cancer", "immune response". References from full-text articles were screened for additional studies. KEY CONTENT AND FINDINGS: Most meta-analyses found that HIPEC improved survival in patients with OC and none of the meta-analyses showed that addition HIPEC to surgery was associated with a worse treatment outcome compared to surgery alone. Positive effect on treatment outcome was found more common in first-line treatment than recurrent disease. Positive effect on treatment outcome was more common in first-line treatment (especially during interval debulking surgery) than recurrent disease. HIPEC efficacy can be affected by patients' characteristics (BRCA status, platinum sensitivity), cytostatic type and dose, intensity of hyperthermia and peritoneal flow characteristics. Apart from strict cytotoxic effect, HIPEC can induce anti-cancer immune response. CONCLUSIONS: Although factors confounding HIPEC efficacy are not well-defined, survival improvement, related to addition HIPEC to surgery in OC, was observed. Future studies should focus on determining a subgroup of patients, who benefit from HIPEC. This will contribute to the unification of European and American recommendations.

Obstetric Results after Fertility-Sparing Management of Non-Epithelial Ovarian Cancer.

PURPOSE: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. METHODS: The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. RESULTS: The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients' age was related to the chance of childbearing. CONCLUSIONS: The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant.

Assessment of Hospital Volume in the Surgical Management of Endometrial and Ovarian Cancer: A Polish Population-Based Study.

BACKGROUND Surgery is a cornerstone in management of ovarian and endometrial cancer. The European Society of Gynecological Oncology introduced quality indicators to improve management of these cancers. The optimal annual number of surgeries per unit was established for high-quality surgical treatment. MATERIAL AND METHODS The database of the National Health Fund on surgical management of endometrial and ovarian cancer was analyzed. Patients treated between 2017 and 2020 were included. Departments where patients underwent surgery were divided according to number of surgeries performed per year in endometrial cancer: ≥80, 79-50, 49-20, 19-0; and ovarian cancer: ≥100, 99-50, 49-20, 19-0. Optimal number of surgeries per center was defined as at least 100 and 80 surgeries per year in ovarian and endometrial cancer, respectively. RESULTS Totally, there were 22 325 surgeries in 316 units and 10 381 surgeries in 251 units due to endometrial and ovarian cancer, respectively. Most surgeries in endometrial cancer (n=15 077; 67.5%) and ovarian cancer (n=9642; 92.88%) were performed in departments that did not meet optimal criteria in number of surgeries. Between 2017 and 2019, an increasing trend in number of surgeries per year in endometrial and ovarian cancer was found. In 2020, there was a decrease in the number of surgeries by 7.8% (n=453) and 8.6% (n=234) in endometrial and ovarian cancer, respectively. CONCLUSIONS In Poland, surgical treatment of ovarian and endometrial cancer is decentralized. Most cancer patients underwent surgery in low-volume general gynecologic departments. The COVID-19 pandemic impaired cancer management, leading to a decreased number of surgeries.

PROM1, CXCL8, RUNX1, NAV1 and TP73 genes as independent markers predictive of prognosis or response to treatment in two cohorts of high-grade serous ovarian cancer patients.

Considering the vast biological diversity and high mortality rate in high-grade ovarian cancers, identification of novel biomarkers, enabling precise diagnosis and effective, less aggravating treatment, is of paramount importance. Based on scientific literature data, we selected 80 cancer-related genes and evaluated their mRNA expression in 70 high-grade serous ovarian cancer (HGSOC) samples by Real-Time qPCR. The results were validated in an independent Northern American cohort of 85 HGSOC patients with publicly available NGS RNA-seq data. Detailed statistical analyses of our cohort with multivariate Cox and logistic regression models considering clinico-pathological data and different TP53 mutation statuses, revealed an altered expression of 49 genes to affect the prognosis and/or treatment response. Next, these genes were investigated in the validation cohort, to confirm the clinical significance of their expression alterations, and to identify genetic variants with an expected high or moderate impact on their products. The expression changes of five genes, PROM1, CXCL8, RUNX1, NAV1, TP73, were found to predict prognosis or response to treatment in both cohorts, depending on the TP53 mutation status. In addition, we revealed novel and confirmed known SNPs in these genes, and showed that SNPs in the PROM1 gene correlated with its elevated expression.

Obstetric outcomes after conservative management of ovarian borderline tumors in women of reproductive age: A single center experience.

OBJECTIVE: The main goal of fertility-sparing treatment is pregnancy followed by live birth (i.e., successful pregnancy). The principal objective of our study was to evaluate the successful pregnancy rate in patients with borderline ovarian tumors (BOTs) after conservative treatment. The second goal was to evaluate the safety of the conservative approach. STUDY DESIGN: 110 patients with BOT were retrospectively evaluated. All patients underwent surgical treatment, sparing the uterus and part of at least one ovary. RESULTS: The median age was 28 years (range 17-40 years). Serous and mucinous tumors were found in 63 (57%) and 34 (31%) women, respectively. FIGO stage I, II, and III was diagnosed in 101 (91.8%), 3 (2.7%), and 6 (5.5%) patients, respectively. The 3- and 5-year progression-free survival was 82.5% and 78.2%, respectively. Recurrent disease was treated conservatively in 14 women, whereas 3 patients underwent radical surgery. Fifty-six (50.9%) patients got pregnant and had at least one live birth. A total of 83 children were born. A significant difference in the successful pregnancy rate was found in patients diagnosed ≤ 35 years vs. > 35 years old (55.6% vs. 9.1%, respectively; p = 0.003). Surgical approach (laparoscopy vs. laparotomy) did not influence the chance of childbirth. Pre-term delivery constituted 6.25% of all births. CONCLUSIONS: Fertility-sparing surgery should be proposed to young women wishing to preserve fertility. The rate of spontaneous pregnancy is approximately 50%.The risk of relapse is significant but always of borderline histology and may be successfully treated by the second surgery.

Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer.

OBJECTIVES: The objective of the study was to assess the usefulness of determining HE4 and CA125 in ovarian cancer patients, to indicate which of the measurements may be optimal in the prognosis, depending on the treatment scheme. MATERIAL AND METHODS: The concentrations of CA125 and HE4 were performed in 70 patients with advanced ovarian cancer during I-line therapy and after treatment. The subjects were divided based on the treatment scheme: group I - primary surgery and adjuvant chemotherapy, II- neoadjuvant therapy, and surgery. RESULTS: Multivariate analysis showed that HE4 levels six months after treatment was significantly higher in patients with disease progression. ROC analysis in the group of patients treated with neoadjuvant therapy showed that the cut-off values indicating relapse for HE4 and CA125 after six months of follow up, were > 90.4 pmol/L, > 25.6 IU/mL, respectively. In the group of patients not treated with neoadjuvant therapy, the cut-off points differentiating patients with progression were: HE4 > 79.1 pmol/L, CA125 > 30.7 IU/mL. We demonstrated significantly higher HE4 and CA125 at both 6- and 12-months follow-up in patients treated with neoadjuvant therapy. In both groups of patients, the cut-off points were lower than those proposed by the manufacturer of the kits. CONCLUSIONS: Measurement of HE4 six months after treatment may be useful in identifying patients at high risk of progression, especially when CA125 levels may be non-specifically elevated. The cut-off values indicating relapse for HE4 and CA125 after six months of follow up may be lower than the normal range.

The results of different fertility-sparing treatment modalities and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia: Case series of 30 patients and systematic review.

OBJECTIVE: Increasing incidence of endometrial cancer and late motherhood enhance conservative management in clinical practice. Although different approaches to fertility-sparing treatment are possible, it is still unknown which patients will benefit more from systemic or local treatment. Aim of this paper is to analyze the effectiveness of different methods of conservative management and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia. STUDY DESIGN: 30 patients (10 with atypical endometrial hyperplasia, 20 with endometrial cancer) treated conservatively were included to retrospective analysis. 24 patients receiving progestins were divided into 2 groups according to the dose (low and high dose); 6 patients were treated with levonorgestrel releasing intrauterine device. Effectiveness of therapy (complete, partial or absent) and obstetric outcomes (number of pregnancies and live births) were assessed. Electronic databases (MEDLINE, Web of Science, Embase) were searched for articles according to criteria: 1) fertility-sparing treatment of endometrial cancer/atypical endometrial hyperplasia in patients of reproductive age, 2) assessment of pregnancy/obstetric results. The risk of bias was assessed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Series. RESULTS: Complete and partial remission were achieved in 21 and 3 patients, respectively. 6 patients did not respond to treatment. Relapse was diagnosed in 6 patients. Probability of complete remission according to low-, high-dose regimen and levonorgestrel-releasing intrauterine device were 55.6% (46.5%-64.7%), 73.3% (65.2%-81.4%) and 83.3% (76.5%-90.1%) respectively. 4 patients get pregnant and 3 of them born children. 25 studies (21 retrospective, 4 prospective) with 812 participants were included in the systematic review. The most studied was progestin based treatment. Complete and partial response to fertility-sparing management was diagnosed in 634 and 38 patients, respectively. Relapse was diagnosed in 170 patients. Median times of follow-up range from 17 (1-45) to 98 (35-176) months. The total number of pregnancies and live births were 352 and 246, respectively. CONCLUSIONS: Fertility-sparing treatment is a safe method of management in young women with endometrial cancer/atypical endometrial hyperplasia. While the main goal of conservative management is preserving the possibility of having children, only a small number of women will become pregnant and give birth.

Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas.

OBJECTIVE: DNA repair pathways are potential targets of molecular therapy in cancer patients. The FANCD2, BRIP1, BRCA1/2, and FANCF genes are involved in homologous recombination DNA repair, which implicates their possible role in cell response to DNA-damaging agents. We evaluated a clinical significance of pre-treatment expression of these genes at mRNA level in 99 primary, advanced-stage ovarian carcinomas from patients, who later received taxane-platinum (TP) or platinum-cyclophosphamide (PC) treatment. METHODS: Gene expression was determined with the use of Real-Time PCR. The BRCA2 and BRIP1 gene sequence was investigated with the use of SSCP, dHPLC, and PCR-sequencing. RESULTS: Increased FANCD2 expression occurred to be a negative prognostic factor for all patients (PC+TP:HR 3.85, p = 0.0003 for the risk of recurrence; HR 1.96, p = 0.02 for the risk of death), and this association was even stronger in the TP-treated group (HR 6.7, p = 0.0002 and HR 2.33, p = 0.01, respectively). Elevated BRIP1 expression was the only unfavorable molecular factor in the PC-treated patients (HR 8.37, p = 0.02 for the risk of recurrence). Additionally, an increased FANCD2 and BRCA1/2 expression levels were associated with poor ovarian cancer outcome in either TP53-positive or -negative subgroups of the TP-treated patients, however these groups were small. Sequence analysis identified one protein truncating variant (1/99) in BRCA2 and no mutations (0/56) in BRIP1. CONCLUSIONS: Our study shows for the first time that FANCD2 overexpression is a strong negative prognostic factor in ovarian cancer, particularly in patients treated with TP regimen. Moreover, increased mRNA level of the BRIP1 is a negative prognostic factor in the PC-treated patients. Next, changes in the BRCA2 and BRIP1 genes are rare and together with other analyzed FA genes considered as homologous recombination deficiency may not affect the expression level of analyzed genes.

Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.

OBJECTIVE: TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas. METHODS: Statistical analyses were done with the Kaplan-Meier method, log-rank test, the Cox's and logistic regression models for all patients, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively). RESULTS: Forty of 159 ovarian carcinomas (25.2%) were diagnosed in patients with BRCA1 germline mutations; 102 tumors (64.2%) were TP53+ and 57 (37.8%) were TP53-. Among patients with TP53+ carcinomas, BRCA1 carriers had increased odds of recurrence compared with sporadic cases (HR 2.25, P=0.003; median disease-free survival time 7.7 vs. 18.4months, respectively). In the smaller TP53- subgroup, BRCA1 mutation reduced the risk of death by 46% (HR 0.54, P=0.099, median overall survival time 42.7 vs. 28.1months), but beyond the border of significance. When the TP53 status was not taken into account, BRCA1 mutations did not show any significance, however, there was a trend toward increased odds of complete remission for women with BRCA1 mutations compared to non-carriers (OR 2.47, P=0.064). Taxane-platinum therapy showed advantage over the platinum-cyclophosphamide one in the entire group of patients and in the TP53+ subgroup. CONCLUSIONS: Our results suggest that the TP53 accumulation status determines the prognosis of BRCA1 mutation carriers with high-grade ovarian carcinomas.

Pseudomonas cerasi sp. nov. (non Griffin, 1911) isolated from diseased tissue of cherry.

Eight isolates of Gram-negative fluorescent bacteria (58(T), 122, 374, 791, 963, 966, 970a and 1021) were obtained from diseased tissue of cherry trees from different regions of Poland. The symptoms resembled those of bacterial canker. Based on an analysis of 16S rDNA sequences the isolates shared the highest over 99.9% similarity with Pseudomonas ficuserectae JCM 2400(T) and P. congelans DSM 14939(T). Phylogenetic analysis using housekeeping genes gyrB, rpoD and rpoB revealed that they form a separate cluster and confirmed their closest relation to P. syringae NCPPB 281(T) and P. congelans LMG 21466(T). DNA-DNA hybridization between the cherry isolate 58(T) and the type strains of these two closely related species revealed relatedness values of 58.2% and 41.9%, respectively. This was further supported by Average Nucleotide Identity (ANIb) and Genome-to-Genome Distance (GGDC) between the whole genome sequences of strain LMG 28609(T) and closely related Pseudomonas species. The major cellular fatty acids are 16:0 and summed feature 3 (16:1 ω7c/15:0 iso 2OH). Phenotypic characteristics differentiated the novel isolates from other closely related species. The G+C content of the genomic DNA of strain 58(T) was 59%. The diversity was proved by PCR MP and BOX PCR, eliminating the possibility that they constitute a clonal population. Based on the evidence of this polyphasic taxonomic study the eight strains are considered to represent a novel species of the genus Pseudomonas for which the name P. cerasi sp. nov. (non Griffin, 1911) is proposed. The type strain of this species is 58(T) (=LMG 28609(T)=CFBP 8305(T)).

The Evaluation of Risk Factors Associated With Relapse and Recurrence of Borderline Ovarian Tumors With Long-Term Follow-up.

OBJECTIVE: The goal was to analyze the risk factors of relapse and to compare the type of recurrence in patients with borderline tumors treated and followed up in Oncologic Center in Warsaw. MATERIALS AND METHODS: This is a retrospective-prospective cohort study of 307 patients with confirmed borderline ovarian tumors treated in the Maria Sklodowska-Curie Memorial Cancer Center in Warsaw between 1994 and 2010. Univariate and multivariate analysis as well as Kaplan-Meier estimates were used to explore the impact of different covariates on progression-free survival. The analysis included the following potential prognostic factors: age, CA 125 value, stage according to classification of the International Federation of Gynecology and Obstetrics (FIGO), methods and radicality of operation, staging, tumor capsule rupture, histopathology, implants, ascites, and microinvasion. The analysis of relapses was also performed. RESULTS: Univariate analysis showed the negative impact of 2 factors on progression-free survival: FIGO II/III (implants) (P = 0.011) and ascites (P = 0.027). The multivariate analyses showed the detrimental effect of FIGO Ic (HR, 2.63; 95% confidence interval [CI], 1.12-6.17, P = 0.027), FIGO II or III (implants) (HR, 3.67; 95% CI, 1.56-8.61, P = 0.003), and incomplete staging (HR, 3.63; 95% CI, 1.09-12.07, P = 0.035), but not ascites (P > 0.1). Relapse occurred in 32 (10%) patients: in 22 patients as borderline and in 10 patients as invasive tumor. Seven (70%) patients with invasive relapse died of disease. All patients with borderline relapses were successfully managed by second surgery, which in 80% was again conservative. CONCLUSIONS: Relapses in borderline ovarian tumor are uncommon, in 10% of patients. Invasive relapses are rare, only in 3% of patients, but often with fatal course irrespective of the treatment applied. The most important clinical risk factors of relapse are implants (FIGO II/III), FIGO Ic, and incomplete staging and this patients as well as patients with ascites should be closely followed. Relapses of borderline histology are easily detected and successfully managed by surgery.

Antagonistic potential of Pseudomonas graminis 49M against Erwinia amylovora, the causal agent of fire blight.

In a previous study (Mikicinski et al. in Eur J Plant Pathol, doi: 10.1007/s10658-015-0837-y , 2015), we described the characterization of novel strain 49M of Pseudomonas graminis, isolated from the phyllosphere of apple trees in Poland showing a good protective activity against fire blight on different organs of host plants. We now report investigations to clarify the basis for this activity. Strain 49M was found to produce siderophores on a medium containing complex CAS-Fe(3+) and HDTMA, but was not able to produce N-acyl homoserine lactones (AHLs). Moreover, it formed a biofilm on polystyrene and polyvinyl chloride (PVC) surfaces. Strain 49M gave a positive reaction in PCR with primers complementary to gacA, the regulatory gene influencing the production of several secondary metabolites including antibiotics. The genes prnD (encoding pyrrolnitrin), pltC, pltB (pyoluteorin), phlD (2,4-diacetyl-phloroglucinol) and phzC as well as phzD (and their homologs phzF and phzA encoding phenazine), described for antagonistic fluorescent pseudomonads, however, were not detected. Research into the biotic relationship between strain 49M and Erwinia amylovora strain Ea659 on five microbiological media showed that this strain clearly inhibited the growth of the pathogen on King's B and nutrient agar with glycerol media, to a very small extent on nutrient agar with sucrose, and not at all on Luria-Bertani agar. On medium 925, strain 49M even stimulated E. amylovora growth. The addition of ferric chloride to King's B resulted in the loss of its inhibitory ability. Testing the survival of 49M in vitro showed its resistance to drought, greater than that of E. amylovora.

Development of SCAR markers for rapid and specific detection of Pseudomonas syringae pv. morsprunorum races 1 and 2, using conventional and real-time PCR.

Specific primers were developed to detect the causal agent of stone fruit bacterial canker using conventional and real-time polymerase chain reaction (PCR) methods. PCR melting profile (PCR MP) used for analysis of diversity of Pseudomonas syringae strains, allowed to pinpoint the amplified fragments specific for P. syringae pv. morsprunorum race 1 (Psm1) and race 2 (Psm2), which were sequenced. Using obtained data, specific sequence characterised amplified region (SCAR) primers were designed. Conventional and real-time PCRs, using genomic DNA isolated from different bacterial strains belonging to the Pseudomonas genus, confirmed the specificity of selected primers. Additionally, the specificity of the selected DNA regions for Psm1 and Psm2 was confirmed by dot blot hybridisation. Conventional and real-time PCR assays enabled accurate detection of Psm1 and Psm2 in pure cultures and in plant material. For conventional PCR, the detection limits were the order of magnitude ~10(0) cfu/reaction for Psm1 and 10(1) cfu/reaction for Psm2 in pure cultures, while in plant material were 10(0)-10(1) cfu/reaction using primers for Psm1 and 3 × 10(2) cfu/reaction using primers for Psm2. Real-time PCR assays with SYBR Green I showed a higher limit of detection (LOD) - 10(0) cfu/reaction in both pure culture and in plant material for each primer pairs designed, which corresponds to 30-100 and 10-50 fg of DNA of Psm1 and Psm2, respectively. To our knowledge, this is the first PCR-based method for detection of the causal agents of bacterial canker of stone fruit trees.

Clinical value of human epididymis protein 4 and the Risk of Ovarian Malignancy Algorithm in differentiating borderline pelvic tumors from epithelial ovarian cancer in early stages.

OBJECTIVE: The clinical value of human epididymis protein 4 (HE4) and the possibility of its use in the differential diagnosis in patients with benign, borderline and epithelial ovarian cancer in early International Federation of Gynaecology and Obstetrics (FIGO) stages. STUDY DESIGN: The study group consisted of 205 women, including 60 with ovarian cancer, 18 with borderline tumors, 77 with benign lesions and 50 healthy subjects. In all the patients, before the treatment and in control groups, we determined CA 125 and HE4 in serum by electrochemiluminescence on the basis of the COBAS e601 system. For comparison of two independent groups, we used the U Mann-Whitney test. The analysis of the diagnostic power of the assessed parameters has been determined using the MedCalc statistical program. The probability of disease free survival (DFS) was evaluated using the log-rank test and Cox regression model. RESULTS: Concentrations of HE4, CA 125 and Risk of Ovarian Malignancy Algorithm (ROMA) value were significantly higher in early ovarian cancer than in patients with benign (P<0.0001) and borderline tumors (P<0.002), the receiver operating characteristics (ROC) curves, demonstrated the highest diagnostic sensitivity for the ROMA score, as well post (AUC=0.817) as pre-menopausal (AUC=0.806). HE4 concentrations (P<0.021) and the value of the ROMA score (P<0.004) were significantly higher in patients with relapse than in patients in remission. There was no connection between concentrations of the studied tumor markers and DFS. CONCLUSIONS: Determination of HE4 serum concentrations has a significant clinical value, especially in patients with benign lesions and elevated CA 125 levels. The combined assessment of HE4, CA 125 and the ROMA algorithm is helpful in differentiating benign tumors and borderline pelvic tumors from epithelial ovarian cancer in early FIGO stages. Determination of HE4, CA 125 and ROMA algorithm is not helpful in differentiating patients with borderline from benign lesions.

Morphological and biochemical characterization of Erwinia amylovora-induced hypersensitive cell death in apple leaves.

In attached apple leaves, spot-inoculated with Erwinia amylovora, the phenotypic appearance of the hypersensitive response (HR) and the participation of ethylene, reactive oxygen species (ROS) and of vacuolar processing enzyme (VPE) (a plant caspase-1-like protease) were analysed. The HR in both the resistant and susceptible genotypes expressed a similar pattern of distinguishable micro HR lesions that progressed into confined macro HR lesions. The HR symptoms in apple were compared to those in non-host tobacco. The morphology of dead cells (protoplast shrinkage and retraction from cell wall) in apple leaves resembled necrotic programmed cell death (PCD). Lesion formation in both cv. Free Redstar (resistant) and cv. Idared (highly susceptible) was preceded by ROS accumulation and elevation of ethylene levels. Treatment of infected leaves with an inhibitor of ethylene synthesis led to a decrease of ethylene emission and suppression of lesion development in both cultivars. In the resistant but not in the susceptible apple cultivar an early and late increase in VPE gene expression was detected. This suggests that VPE might be an underlying component of the response to E. amylovora in resistant apple cultivars. The findings show that in the studied pathosystem the cell death during the HR proceeds through a signal transduction cascade in which ROS, ethylene and VPE pathways play a role.

[Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico-pathomorphological analysis of the cases and literature review]. / Guz gladkomiesniowy o nieokreslonym potencjale zlosliwosci (STUMP)--analiza kliniczno-patomorfologiczna przypadków oraz przeglad pismiennictwa.

OBJECTIVES: This retrospective study was designed to evaluate the clinical and pathological features and outcomes of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). MATERIAL AND METHODS: Ten patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the institution databases. Variables of interest included histopathological details, age at diagnosis, types of treatment and recurrence rate. RESULTS: The mean age at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16 months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm. Uterine bleeding was the second most frequent symptom observed in this cohort In three cases conservative procedure was performed, whereas in other patients hysterectomy was performed. No recurrence was observed during the follow-up period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or severe type, and in 3 cases necrosis was observed. In half of the tumors expression of TP53 was found, and value of MIB 1 was estimated at 2-35%. CONCLUSIONS: STUMP should be diagnosed by experienced pathologists due to the fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of these tumors allows to consider a conservative management in patients wishing to preserve fertility

Evaluation of selected ultrasonographic parameters and marker levels in the preoperative differentiation of borderline ovarian tumors and ovarian cancers.

OBJECTIVES: In young patients with borderline tumors the fertility-sparing treatment is indicated, thus the preoperative investigation is important. The aim of this study was to perform a comparative assessment of sensitivity and specificity of selected ultrasonographic and clinical parameters for the diagnoses of borderline tumors and ovarian cancers. METHODS: We retrospectively analyzed 57 patients who underwent surgical treatment in the Maria Sklodowska-Curie Memorial Cancer Center from Jan 01, 2008 to Dec 31, 2009. Ovarian cancers were diagnosed in 41 patients, and borderline ovarian tumors in 16 patients. Statistical model was developed to determine independent predictive factors that would be useful in preoperative differentiation between both tumors. The model included the following factors: menopausal status, tumor morphology, wall thickness (including outgrowths), septal thickness, echogenicity, resistive index, serum CA-125 level, and free fluid in the peritoneal cavity. RESULTS: Based on the statistical model developed, independent predictive factors in the differentiation between ovarian cancers and borderline tumors included the menopausal status (P=0.005), tumor echogenicity (P=0.047) and the presence of free fluid in the Douglas pouch (P=0.043). With the cutoff value of 13 (with scores below 13 indicating a borderline ovarian tumor, and scores of ≥13 indicating ovarian cancer), sensitivity was 90.2% and specificity was 87%. CONCLUSIONS: Our proposed model of preoperative evaluation has a sensitivity of 90% in the differentiation between ovarian cancers and borderline tumors. When combined with intraoperative findings, it allows optimal surgical therapeutic decisions to be made in patients with borderline ovarian tumors.

Clinical and histopathological factors in patients with cervical cancer allowing to identify candidates for less radical surgery.

OBJECTIVE: To determine clinical and histopathological factors in patients with cervical cancer tumors smaller than 2 cm in order to identify those who could be operated less extensively with preservation of reproductive organs and lower morbidity. MATERIAL AND METHODS: We retrospectively reviewed the records of patients with cervical cancer and a maximum tumor of 2cm in diameter who were qualified for primary surgery in the years 2001-2007 at the Department of Gynecologic Oncology Cancer Center in Warsaw. RESULTS: From the group of 110 operated patients, 96 were included into the study Within the analyzed group the infiltration of the parametrium was found in 4 women (4.2%). All of them had squamous cell cancer; stage IB, grade G3. One patient had a tumor 1.5 cm in diameter and 3 patients had tumors up to 2 cm in diameter. The involvement of lymph nodes was observed in 3 patients with squamous cell carcinoma: in one case the tumor was intermediate grade (G2) and in two cases low grade (G3). The lymph nodes were involved only in patients with tumors greater than 0.5 cm. The lymph vascular space invasion was found in 14 patients (14.7%): in 12 with squamous cell cancer and in 2 with adenocarcinoma. The diameter of the tumor was 0.5-1 cm in 4 women, 1-1.4 cm in 3 women and 1.5-2 cm in the majority (7 women accounted for 29% of all patients in that group). No infiltration of the blood vessels could be seen in all 30 women with tumors smaller than 0.5 cm. We found a statistically significant relationship between the size of the tumor and the incidence of lymph vascular space invasion (p=0.024). CONCLUSION: In selective cases fertility organ preserving surgery is possible and safe. In the group of patients with tumor less than 5 mm in diameter no parametrium involvement or lymph metastases were observed. In such situation cervical conisation can be justified. In well-differentiated (G1) tumors less than 2 cm in diameter less radical surgical procedures can also be performed because no treatment failure has been observed.

Rhizobium skierniewicense sp. nov., isolated from tumours on chrysanthemum and cherry plum.

Three isolates of Gram-negative, rod-shaped, non-spore-forming bacteria were recovered from galls on chrysanthemum (Chrysanthemum L.; Ch11T, Ch12) and cherry plum (Prunus cerasifera var. divaricata; AL9.3). All three isolates were able to cause crown galls on various plant species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the three isolates were probably identical (100% sequence similarity) and closely related to Rhizobium rubi (99.6 %), Rhizobium radiobacter (98.7 %) and Rhizobium larrymoorei (98.1 %). Similar analysis based on the housekeeping genes glnA, gyrB and rpoB also indicated that the novel isolates were identical and closely related to R. rubi. The major cellular fatty acids of strain Ch11T were C18:1ω7c (62.1 %), summed feature 2 (comprising C12:0 aldehyde, iso-C16:1 I and/or C14:0 3-OH; 10.8 %), summed feature 3 (comprising C16:1ω7c and/or iso-C15:0 2-OH; 7.7 %) and C10:0 3-OH (7.5 %). However, the DNA-DNA relatedness between Ch11T and R. rubi LMG 156T was only 48 % and, unlike phylogenetically related established Rhizobium species, the novel isolates were able to utilize ß-hydroxybutyric acid but not L-fucose. Based on the phylogenetic and phenotypic evidence, the isolates are considered to represent a single novel species of the genus Rhizobium, for which the name Rhizobium skierniewicense sp. nov. is proposed; the type strain is Ch11T (=LMG 26191T=CFBP 7420T).