DDASSQ: An open-source, multiple peptide sequencing strategy for label free quantification based on an OpenMS pipeline in the KNIME analytics platform.

In this study we investigated the performance of a computational pipeline for protein identification and label free quantification (LFQ) of LC-MS/MS data sets from experimental animal tissue samples, as well as the impact of its specific peptide search combinatorial approach. The full pipeline workflow was composed of peptide search engine adapters based on different identification algorithms, in the frame of the open-source OpenMS software running within the KNIME analytics platform. Two different in silico tryptic digestion, database-search assisted approaches (X!Tandem and MS-GF+), de novo peptide sequencing based on Novor and consensus library search (SpectraST), were tested for the processing of LC-MS/MS raw data files obtained from proteomic LC-MS experiments done on proteolytic extracts from mouse ex vivo liver samples. The results from proteomic LFQ were compared to those based on the application of the two software tools MaxQuant and Proteome Discoverer for protein inference and label-free data analysis in shotgun proteomics. Data are available via ProteomeXchange with identifier PXD025097.

Taylor's Law in Innovation Processes.

Taylor's law quantifies the scaling properties of the fluctuations of the number of innovations occurring in open systems. Urn-based modeling schemes have already proven to be effective in modeling this complex behaviour. Here, we present analytical estimations of Taylor's law exponents in such models, by leveraging on their representation in terms of triangular urn models. We also highlight the correspondence of these models with Poisson-Dirichlet processes and demonstrate how a non-trivial Taylor's law exponent is a kind of universal feature in systems related to human activities. We base this result on the analysis of four collections of data generated by human activity: (i) written language (from a Gutenberg corpus); (ii) an online music website (Last.fm); (iii) Twitter hashtags; (iv) an online collaborative tagging system (Del.icio.us). While Taylor's law observed in the last two datasets agrees with the plain model predictions, we need to introduce a generalization to fully characterize the behaviour of the first two datasets, where temporal correlations are possibly more relevant. We suggest that Taylor's law is a fundamental complement to Zipf's and Heaps' laws in unveiling the complex dynamical processes underlying the evolution of systems featuring innovation.

Are delusional contents replayed during dreams?

The relationship between dream content and waking life experiences remains difficult to decipher. However, some neurobiological findings suggest that dreaming can, at least in part, be considered epiphenomenal to ongoing memory consolidation processes in sleep. Both abnormalities in sleep architecture and impairment in memory consolidation mechanisms are thought to be involved in the development of psychosis. The objective of this study was to assess the continuity between delusional contents and dreams in acutely psychotic patients. Ten patients with a single fixed and recurring delusional content were asked to report their dreams during an acute psychotic break. Sixteen judges with four different levels of acquaintance to the specific content of the patients' delusions were asked to group the dreams, expecting that fragments of the delusional thought would guide the task. A mathematical index (f,t) was developed in order to compare correct groupings between the four groups of judges. Most judges grouped the dreams slightly above chance level and no relevant differences could be found between the four groups [F(3,12)=1.297; p=n.s.]. Scoring of dreams for specific delusional themes suggested a continuity in terms of dream and waking mentation for two contents (Grandiosity and Religion). These findings seem to suggest that at least some delusional contents recur within patients' dreams. Future studies will need to determine whether such continuity reflects ongoing consolidation processes that are relevant to current theories of delusion formation and stabilization.

Interacting innovation processes.

In this work, we introduce a general model for a collection of innovation processes in order to model and analyze the interaction among them. We provide theoretical results, analytically proven, and we show how the proposed model fits the behaviors observed in some real data sets (from Reddit and Gutenberg). It is worth mentioning that the given applications are only examples of the potentialities of the proposed model and related results: due to its abstractness and generality, it can be applied to many interacting innovation processes.

Inhalation versus endovenous sedation in subarachnoid hemorrhage patients: effects on regional cerebral blood flow.

OBJECTIVE: Isoflurane is a volatile anesthetic that has a vasodilating effect on cerebral vessels producing a cerebral blood flow increase. Furthermore, it has been shown in animal studies that isoflurane, when used as a preconditioning agent, has neuroprotective properties, inducing tolerance to ischemia. However, it is not routinely used in neurointensive care because of the potential increase in intracranial pressure caused by the rise in cerebral blood flow. Nevertheless, subarachnoid hemorrhage patients who are at risk for vasospasm may benefit from an increase in cerebral blood flow. We measured regional cerebral blood flow during intravenous sedation with propofol and during sedation with isoflurane in patients with severe subarachnoid hemorrhage not having intracranial hypertension. DESIGN: The study is a crossover, open clinical trial (NCT00830843). SETTING: Neurointensive care unit of an academic hospital. PATIENTS: Thirteen patients with severe subarachnoid hemorrhage, (median Fisher scale 4), monitored on clinical indication with intracranial pressure device and a thermal diffusion probe for the assessment of regional cerebral blood flow. An intracranial pressure>18 mm Hg was an exclusion criterion. INTERVENTIONS: Cerebral and hemodynamic variables were assessed at three steps. Step 1: sedation with propofol 3-4 mg/kg/hr; step 2: after 1 hr of propofol discontinuation and isoflurane 0.8%; step 3: after 1 hr of propofol at the same previous infusion rate. Cerebral perfusion pressure and arterial PCO2 were maintained constant. Mean cerebral artery flow velocity and jugular vein oxygen saturation were measured at the end of each step. MEASUREMENTS AND MAIN RESULTS: Regional cerebral blood flow increased significantly during step 2 (39.3±29 mL/100 hg/min) compared to step 1 (20.8±10.7) and step 3 (24.7±8). There was no difference in regional cerebral blood flow comparing step 1 vs. step 3. No significant difference in intracranial pressure, mean cerebral artery transcranial Doppler velocity, PaCO2, cerebral perfusion pressure between the different steps. CONCLUSIONS: Isoflurane increases regional cerebral blood flow in comparison to propofol. Intracranial pressure did not change significantly in the population not affected by intracranial hypertension.

Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment.

OBJECTIVE: Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC). METHODS: Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model. RESULTS: 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01-1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19-2.56), residual disease (RD) >1 cm (HR: 2.46; 95%CI: 1.74-3.53), and stage IV (HR: 1.93; 95% CI: 1.51-2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age ≥ 75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit. CONCLUSIONS: Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy.

Twitter as an innovation process with damping effect.

In the existing literature about innovation processes, the proposed models often satisfy the Heaps' law, regarding the rate at which novelties appear, and the Zipf's law, that states a power law behavior for the frequency distribution of the elements. However, there are empirical cases far from showing a pure power law behavior and such a deviation is mostly present for elements with high frequencies. We explain this phenomenon by means of a suitable "damping" effect in the probability of a repetition of an old element. We introduce an extremely general model, whose key element is the update function, that can be suitably chosen in order to reproduce the behaviour exhibited by the empirical data. In particular, we explicit the update function for some Twitter data sets and show great performances with respect to Heaps' law and, above all, with respect to the fitting of the frequency-rank plots for low and high frequencies. Moreover, we also give other examples of update functions, that are able to reproduce the behaviors empirically observed in other contexts.

A Semiautomatic Multi-Label Color Image Segmentation Coupling Dirichlet Problem and Colour Distances.

Image segmentation is an essential but critical component in low level vision, image analysis, pattern recognition, and now in robotic systems. In addition, it is one of the most challenging tasks in image processing and determines the quality of the final results of the image analysis. Colour based segmentation could hence offer more significant extraction of information as compared to intensity or texture based segmentation. In this work, we propose a new local or global method for multi-label segmentation that combines a random walk based model with a direct label assignment computed using a suitable colour distance. Our approach is a semi-automatic image segmentation technique, since it requires user interaction for the initialisation of the segmentation process. The random walk part involves a combinatorial Dirichlet problem for a weighted graph, where the nodes are the pixel of the image, and the positive weights are related to the distances between pixels: in this work we propose a novel colour distance for computing such weights. In the random walker model we assign to each pixel of the image a probability quantifying the likelihood that the node belongs to some subregion. The computation of the colour distance is pursued by employing the coordinates in a colour space (e.g., RGB, XYZ, YCbCr) of a pixel and of the ones in its neighbourhood (e.g., in a 8-neighbourhood). The segmentation process is, therefore, reduced to an optimisation problem coupling the probabilities from the random walker approach, and the similarity with respect the labelled pixels. A further investigation involves an adaptive preprocess strategy using a regression tree for learning suitable weights to be used in the computation of the colour distance. We discuss the properties of the new method also by comparing with standard random walk and k-means approaches. The experimental results carried on the White Blood Cell (WBC) dataset and GrabCut datasets show the remarkable performance of the proposed method in comparison with state-of-the-art methods, such as normalised random walk and normalised lazy random walk, with respect to segmentation quality and computational time. Moreover, it reveals to be very robust with respect to the presence of noise and to the choice of the colourspace.

A model for the Twitter sentiment curve.

Twitter is among the most used online platforms for the political communications, due to the concision of its messages (which is particularly suitable for political slogans) and the quick diffusion of messages. Especially when the argument stimulate the emotionality of users, the content on Twitter is shared with extreme speed and thus studying the tweet sentiment if of utmost importance to predict the evolution of the discussions and the register of the relative narratives. In this article, we present a model able to reproduce the dynamics of the sentiments of tweets related to specific topics and periods and to provide a prediction of the sentiment of the future posts based on the observed past. The model is a recent variant of the Pólya urn, introduced and studied in Aletti and Crimaldi (2019, 2020), which is characterized by a "local" reinforcement, i.e. a reinforcement mechanism mainly based on the most recent observations, and by a random persistent fluctuation of the predictive mean. In particular, this latter feature is capable of capturing the trend fluctuations in the sentiment curve. While the proposed model is extremely general and may be also employed in other contexts, it has been tested on several Twitter data sets and demonstrated greater performances compared to the standard Pólya urn model. Moreover, the different performances on different data sets highlight different emotional sensitivities respect to a public event.

A Semi-Supervised Reduced-Space Method for Hyperspectral Imaging Segmentation.

The development of the hyperspectral remote sensor technology allows the acquisition of images with a very detailed spectral information for each pixel. Because of this, hyperspectral images (HSI) potentially possess larger capabilities in solving many scientific and practical problems in agriculture, biomedical, ecological, geological, hydrological studies. However, their analysis requires developing specialized and fast algorithms for data processing, due the high dimensionality of the data. In this work, we propose a new semi-supervised method for multilabel segmentation of HSI that combines a suitable linear discriminant analysis, a similarity index to compare different spectra, and a random walk based model with a direct label assignment. The user-marked regions are used for the projection of the original high-dimensional feature space to a lower dimensional space, such that the class separation is maximized. This allows to retain in an automatic way the most informative features, lightening the successive computational burden. The part of the random walk is related to a combinatorial Dirichlet problem involving a weighted graph, where the nodes are the projected pixel of the original HSI, and the positive weights depend on the distances between these nodes. We then assign to each pixel of the original image a probability quantifying the likelihood that the pixel (node) belongs to some subregion. The computation of the spectral distance involves both the coordinates in a features space of a pixel and of its neighbors. The final segmentation process is therefore reduced to a suitable optimization problem coupling the probabilities from the random walker computation, and the similarity with respect the initially labeled pixels. We discuss the properties of the new method with experimental results carried on benchmark images.

Validation of a self-efficacy survey for Italian midwifery students with regard to breastfeeding support.

BACKGROUND: The training of midwives is critical in order to acquire the professional skills necessary in the support of breastfeeding. The use of tools that demonstrate student competency in the field of midwifery is fundamental. OBJECTIVES: The aim for this study was to translate and apply a questionnaire to an Italian cohort of students - determining their self-efficacy and establishing the validity of the tool collectively. DESIGN: This study was a descriptive cross-sectional study. SETTING: The study was conducted at a large university in northern Italy. PARTICIPANTS: Seventy-six female students from the Midwifery Degree Course. METHODS: The questionnaire translated into Italian was administered to students participating in a Midwifery Degree Course. Rasch analysis was applied using ConQuest software, version 4. RESULTS: Seventy-six questionnaires were collected. Fifty-six questionnaires have modal value 3 of the Likert response scale (It's easy for me to do it), 17 have a mode of 4 (It's very easy for me to do it), 3 of 2 (It's difficult for me to do it) and no questionnaire of 1 (It's very difficult for me to do it). A questionnaire identified the perception of self-efficacy of midwifery students in assisting breastfeeding mothers. CONCLUSION: The results of this research demonstrate that students of midwifery consider themselves competent when assisting breast feeding mothers.

Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial.

BACKGROUND: Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality. The aim of this study was to evaluate the usefulness of fenoldopam, a specific agonist of the dopamine-1 receptor, in patients at high risk of perioperative renal dysfunction. METHODS AND RESULTS: A prospective single-center, randomized, double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery. Patients received either fenoldopam at 0.05 microg/kg per minute or dopamine at 2.5 microg/kg per minute after the induction of anesthesia for a 24-hour period. All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score >10. Primary end point was defined as 25% creatinine increase from baseline levels after cardiac surgery. The 2 groups (fenoldopam versus dopamine) were homogeneous cohorts, and no difference in outcome was observed. Acute renal failure was similar: 17 of 40 (42.5%) in the fenoldopam group and 16 of 40 (40%) in the dopamine group (P=0.9). Peak postoperative serum creatinine level, intensive care unit and hospital stay, and mortality were also similar in the 2 groups. CONCLUSIONS: Despite an increasing number of reports of renal protective properties from fenoldopam, we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery.

Clinical significance of a new Q wave after cardiac surgery.

OBJECTIVE: The appearance of new Q waves on the electrocardiogram (ECG) after cardiac surgery has been traditionally considered a sign of major myocardial tissue damage. The aim of this study was to investigate the clinical significance of new Q waves appearing following cardiac surgery and to correlate them with the release of myocardial cell damage biomarkers. METHODS: 206 consecutive patients undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was recorded and cardiac troponin I and creatinekinase subfraction MB assayed the day before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively and every morning until the fifth postoperative day. RESULTS: The incidence of new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful postoperative course; on the contrary, when ECG changes were coupled with the release of myocardial necrosis biomarkers, patients had a complicated postoperative course. CONCLUSIONS: The association of a new Q wave and high levels of myocardial necrosis biomarkers is strongly associated with postoperative cardiac events. On the contrary, the isolated appearance of a new Q wave has no impact on the postoperative cardiac outcome.

A new frontier for quality of care in gynecologic oncology surgery: multi-institutional assessment of short-term outcomes for ovarian cancer using a risk-adjusted model.

OBJECTIVE: To test the feasibility and utility of a risk-adjusted, multicenter outcomes model for ovarian cancer surgery as a tool for quality improvement. METHODS: Patient characteristics, intra-operative findings, procedures, and outcomes were assessed in primary advanced stage ovarian cancer cases from 3 independent centers. A surgical complexity score (SCS) was developed to adjust for extent of surgery. Outcomes measures were: 30-day morbidity (sepsis, thrombo-embolic, cardiac, readmission or re-operation), 3-month mortality, length of stay (LOS), and ability to receive chemotherapy. A multivariable risk-adjusted model was developed for all the outcomes. Observed-to-expected (O/E) outcome ratios were calculated from all data. RESULTS: 564 consecutive patients from 3 centers were analyzed. The strongest predictors of 30-day morbidity were endogenous [albumin (p<0.001) and ASA (p=0.008)] and complexity of surgery [SCS (p<0.001)]. Age (p=0.002) and ASA (p=0.001) independently predicted mortality. LOS independently correlated with age (p=0.007), albumin (p=0.004), SCS (p=0.002), and stage (p=0.024). ASA (p<0.001) and SCS (p=0.003) both impacted ability to receive chemotherapy. Observed to expected (O/E) ratios for dependent outcome variables were similar for all 3 institutions. CONCLUSIONS: We demonstrate the benefits of a national system for studying outcomes in gynecologic surgery using a risk-adjusted model. We specifically find that endogenous patient factors and complexity of surgery are primary drivers of morbidity in ovarian cancer surgery. These data can successfully be used to formulate expected, risk-adjusted rates of complications thus providing a meaningful mechanism to identify areas ripe for quality improvement.

Low-dose interleukin-2 administered pre-operatively to patients with gastric cancer activates peripheral and peritumoral lymphocytes but does not affect prognosis.

BACKGROUND: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. METHODS: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3(+) T, CD4(+) T, CD8(+) T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. RESULTS: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3(+) T and CD4(+) T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. CONCLUSIONS: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.

Myocardial damage prevented by volatile anesthetics: a multicenter randomized controlled study.

OBJECTIVE: The purpose of this study was to evaluate the effects of volatile anesthesia versus total intravenous anesthesia on cardiac troponin release in off-pump coronary artery bypass grafting (OPCAB). DESIGN: The authors performed a multicenter randomized controlled study to compare cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for cardiac surgery on the beating heart, which is an excellent model of human myocardial ischemia. SETTING: Three university hospitals. PARTICIPANTS: The authors randomly assigned 57 patients to desflurane (volatile anesthetic) and 55 patients to propofol (intravenous anesthetic) in addition to an opiate-based anesthesia for OPCAB. INTERVENTIONS: The 2 groups of patients received either desflurane (volatile anesthetic) or propofol in addition to an opiate-based anesthesia for OPCAB. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Prolonged hospitalization was considered as a secondary outcome. MEASUREMENTS AND MAIN RESULTS: Patient mean age was 69 years, and 82% were men. There was a significant (p < 0.001) reduction in postoperative median (25th-75th percentiles) peak of troponin I in patients receiving volatile anesthetics, 1.2 (0.9-1.9) ng/dL, compared with patients receiving total intravenous anesthesia, 2.7 (2.1-4.0) ng/dL. This myocardial protection resulted in a reduced (p = 0.04) number (percentage) of patients requiring postoperative inotropes, 20 (35%) versus 31 (56%), and a reduced number (percentage) of patients submitted to prolonged hospitalization (> or =7 days), 7 (12%) versus 20 (36%) in the 2 groups (p = 0.005). One patient receiving total intravenous anesthesia died within 30 days of surgery. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anesthetics during OPCAB. Because patients underwent cardiac surgery on the beating heart, these results could have implications for cardiac patients undergoing noncardiac surgery.

Perioperative magnesium supplementation to prevent atrial fibrillation after off-pump coronary artery surgery: a randomized controlled study.

OBJECTIVE: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery. DESIGN: Randomized controlled study. SETTING: University teaching hospital. PARTICIPANTS: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups. INTERVENTIONS: Patients in the magnesium group (n = 80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n = 80) received normal saline solution. MEASUREMENTS AND MAIN RESULTS: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p = 0.9). CONCLUSION: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass.

Endometrial cancer: predictors of peritoneal failure.

OBJECTIVE: To assess determinants of peritoneal failure in endometrial cancer patients after definitive primary treatment. METHODS: Of 599 patients with endometrial cancer who had primary surgery at our institution during the decade before 1994, 131 had relapse. We defined "peritoneal failure" as relapse when it occurred in the upper abdomen or involved the pelvic peritoneum (or both). Mean follow-up was 72.8 months. RESULTS: Peritoneal failure was detected in 37 of 599 (6%) patients and represented 28% of identified failures. Stage IV disease, cervical stromal invasion, adnexal involvement, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, lymph node metastasis, histologic grade 3, nonendometrioid histologic subtype, absence of associated hyperplasia, and lymphovascular invasion correlated significantly (P < 0.01) with peritoneal failure. However, on regression analysis, only stage IV disease (P < 0.001, relative risk [RR] = 7.53), nonendometrioid histologic subtype (P = 0.02, RR = 3.01), and cervical stromal invasion (P = 0.04, RR = 2.83) were independent predictors of peritoneal failure. Because 22 of 37 (59%) peritoneal failures were in patients with stage IV disease, we considered separately the 545 patients with stage I-III disease. On regression analysis, nonendometrioid histologic subtype (P < 0.001, RR = 11.58), positive peritoneal cytology (P = 0.009, RR = 6.72), lymph node metastasis (P = 0.02, RR = 5.10), and cervical stromal invasion (P = 0.04, RR = 3.10) were independent predictors of peritoneal failure. Of the 38 patients in whom at least two of these four predictors were positive, 26% had peritoneal failure at 5 years, compared with 1% of the 507 patients who had none or only 1 predictor (P < 0.001). CONCLUSION: Patients with stage IV disease and those with stage I-III disease and at least two of the four independent predictors (nonendometrioid histology, positive peritoneal cytology, cervical stromal invasion, and lymph node metastasis) would be candidates for new therapeutic trials incorporating surgical and adjuvant treatment targeting the entire abdominal cavity.

Predictors of lymphatic failure in endometrial cancer.

OBJECTIVE: The aim of this study was to identify determinants of lymphatic failure in patients with endometrial cancer after definitive primary treatment. METHODS: We observed 142 relapses in endometrial cancer patients who had primary surgery at our institution during the decade before 1994. We defined lymphatic failure as a relapse occurring on the pelvic sidewall (PSW), para-aortic area (PAA), or other node-bearing area (i.e., groin, axilla, supraclavicular, mediastinal). Mean follow-up was 72.8 months. RESULTS: We observed 44 instances of lymphatic failure--6 on the PSW only, 16 in the PAA only, 12 concomitantly in the PAA and on the PSW, and 10 confined in other node-bearing areas. By univariate analysis, body mass index > or = 30 kg/m(2), para-aortic lymph node biopsy, cervical stromal invasion (CSI), positive adnexa, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, positive lymph nodes (pelvic and/or para-aortic), radiotherapy, grade 3 tumor, nonendometrioid histology, and lymph--vascular invasion (LVI) significantly (P < or = 0.05) correlated with lymphatic failure. However, on Cox regression analysis, only LVI (P < 0.01, relative risk [RR] = 4.27), nodal involvement (P = 0.02, RR = 3.43), and CSI (P = 0.049, RR = 2.26) were independent predictors of lymphatic failure. Moreover, lymph node metastases (P = 0.01, RR = 19.82) and CSI (P = 0.050, RR = 3.57) independently predicted failure on the PSW, and only lymph node involvement (P < 0.01, RR = 10.15) predicted relapse in the PAA. CONCLUSION: LVI, positive lymph nodes, and CSI were the strongest predictors of lymphatic failure in endometrial cancer (31% of patients with at least one of the above three variables had a failure at 5 years). Patients with none of the above three factors had an extremely low (<1%) risk of lymphatic failure.

Assessment of prognostic factors in stage IIIA endometrial cancer.

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.