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We conducted a prospective multicenter trial to compare the usefulness of C-11-methionine (MET) and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both C-11-MET and F-18-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either C-11-MET or F-18-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of C-11-MET PET and F-18-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of C-11-MET PET was significantly better than that of F-18-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that C-11-MET PET was superior to F-18-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

Asmaa M Zahran,1 Omnia El-Badawy,2 Lamiaa M Kamel,3 Amal Rayan,4 Khalid Rezk,5 Mona H Abdel-Rahim2 1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 2Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 4Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 5Surgical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, EgyptCorrespondence: Amal Rayan Email amal3774rayan@gmail.com; amalrayan@aun.edu.egBackground and Aim: The present study was conducted to evaluate the number of Tregs in triple negative breast cancer (TNBC), in normal breast parenchyma and in the peripheral blood of these patients and controls, in addition to their correlations with the clinico-pathologic features and the outcomes of TNBC.Methods: Thirty adult treatment-naïve women with non-metastatic TNBC were recruited. In addition, 20 ages matched healthy females participated as a control group. Peripheral blood samples were collected from all participants in tubes containing heparin, fresh tumor tissues were also obtained from all patients undergoing surgery, and 20 normal breast tissue samples were obtained from the same patients’ areas adjacent to the safety margins; all these samples were taken for flow cytometric detection of Tregs.Results: The mean percentages of CD4+CD25+highT cells and Tregs were higher in TNBC peripheral blood than healthy controls and in malignant tissue than normal tissue. Moreover, the frequencies of tumor-infiltrating CD4+T cells and Tregs were exceeding those in the peripheral blood of cancer patients. Only tumor-infiltrating Tregs have shown increasing levels with the increase in the tumor size and were significantly higher in patients with local recurrences than those without recurrence. In addition, Tregs showed significant inverse relation with DFS and direct relation with the level of the peripheral Tregs.Conclusion: The findings of the current study support the possibility that TNBC microenvironment conveys specific characteristics on Tregs distinguishing them from those in normal breast tissue or Tregs in peripheral blood, improving the capabilities of tumor-infiltrating Tregs to enhance tumor growth, local recurrence and reduce the DFS.Keywords: triple negative breast cancer, Tregs, disease free survival, recurrences

Aim: This study aimed to examine the results of the Winograd technique applied in the treatment of ingrown toenail cases, which are frequently encountered in childhood, especially in adolescence. The recurrence, satisfaction, and complication rates in pediatric age groups were evaluated with the surgical matrixectomy application of the Winograd technique, a frequently used one in adult age groups. Materials and Methods: Ingrown toenail cases that had undergone surgical matrixectomy with the Winograd technique between September 2016 and December 2018 were evaluated. Those detected to be stage 2-3 according to the Heifetz classification were operated on. Demographic information was recorded. The cases were divided into three groups as 3-7, 7-12, and >= 12 years as age groups. Such data as recurrence, postoperative infection, osteomyelitis, long term complication and return to regular activity were evaluated. The visual analog scale was used for the satisfaction scale. Results: A total of 162 operated ingrown toenails from 142 children were followed for an average of 21 months (12-38). The mean age of patients was 13.8 years. When the ingrown toenail location was evaluated, the lateral sides (98, 61.2%) of the patients were seen to have been affected more. According to age groups, 65% (105) of the cases were in the group aged 12 years and over. While the frequency of all complications was 8.1% (13), no chronic complications or osteomyelitis were encountered. Recurrence was observed in 3.1% of cases and also early infection (

Management of residual or recurrent disease following thermal ablation of renal cortical tumors includes surveillance, repeat ablation, or surgical extirpation. We present a multicenter experience with regard to the management of this clinical scenario. Prospectively maintained databases were reviewed to identify 1265 patients who underwent cryoablation (CA) or radiofrequency ablation (RFA) for enhancing renal masses. Disease persistence or recurrence was classified into one of the three categories: (i) residual disease in ablation zone; (ii) recurrence in the ipsilateral renal unit; and (iii) metastatic/extra-renal disease. Seventy seven patients (6.1%) had radiographic evidence of disease persistence or recurrence at a median interval of 13.7 months (range, 1–65 months) post-ablation. Distribution of disease included 47 patients with residual disease in ablation zone, 29 with ipsilateral renal unit recurrences (all in ablation zone), and one with metastatic disease. Fourteen patients (18%) elected for surveillance, and the remaining underwent salvage ablation (n = 50), partial nephrectomy (n = 5), or radical nephrectomy (n = 8). Salvage ablation was successful in 38/50 (76%) patients, with 12 failures managed by observation (3), tertiary ablation (6), and radical nephrectomy (3). At a median follow-up of 28 months, the actuarial cancer-specific survival and overall survival in this select cohort of patients was 94.8 and 89.6%, respectively.

Study Objective To assess postoperative recurrence rates in patients with endometriomas managed by either “one-step” CO2 fiber laser vaporization or cystectomy. Design Retrospective study with prospective recording of data. Setting University hospital. Patients One hundred twenty-five patients with symptomatic endometriomas. Interventions Patients underwent a standardized laparoscopic stripping technique (group 1) or cyst vaporization with CO2 fiber laser (group 2). After surgery, patients were incorporated in a prolonged surveillance program with periodic clinical follow-up to check for recurrence of the cyst and/or recurrence of symptoms. Endometrioma recurrence was defined as an ovarian cyst (>10 mm) with a typical aspect arising on the operated ovary identified by transvaginal ultrasound. Measurements and Main Results The primary endpoint was the comparison of recurrence rates between the 2 groups. The secondary endpoint was the evaluation of endometriosis-related pain recurrence in the 2 groups. Other endpoints selected for analysis included the identification of risk factors for the recurrence of endometrioma and of endometriosis-related symptoms. The mean follow-up was 29 ± 13 months (range, 13–49). Recurrence of ovarian endometriosis was recorded in 6.3% of patients (n = 4) treated with cystectomy and in 4.9% of patients (n = 3) managed with CO2 fiber laser (p = .74). Recurrence of endometriosis-related pain was observed in 5 patients (7.8%) in group 1 and in 6 patients (9.8%) in group 2 (p = .67). Mean endometrioma diameter > 5 cm at the time of surgery was identified as the only independent poor prognostic indicator for cyst recurrence (p = .008; odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19–3.32). Moreover, the presence of deep endometriosis at surgery (p = .032; OR, 4.60; 95% CI, 1.14–18.57) and discontinuation of hormonal treatment (p = .015; OR, 3.18; 95% CI, 1.25–8.06) were independent poor prognostic indicators for pain recurrence. Conclusion This study suggests that one-step CO2 fiber laser vaporization may be effective for endometrioma treatment because it is associated with recurrence rates comparable with those occurring after cystectomy, with the advantage of being an ovarian tissue-sparing technique.

Objective To determine the reliability and safety of posterior canal BPPV (pc-BPPV) treatment with subsequent assessment of the effectiveness of the maneuver in a single session, compared to the classic weekly procedure. Method A prospective study of two randomized groups of unilateral pc-BPPV was performed: a weekly management group (27 patients) and single-session treatment group (26 patients). The number of maneuvers required to clear pc-BPPV, incidence of side effects (re-entries and canal conversions), and recurrence rates were compared. Results There were no statistically significant differences in the number of maneuvers needed to resolve pc-BPPV, the incidence of side effects, or the recurrence rate between the two groups. Two re-entries were diagnosed in the single-session group, and both were easily and successfully treated. Three early recurrences were found in the single-session group and one spontaneous recovery was encountered in the weekly group. Time required to discharge patients to follow-up was significantly reduced in the single-session group. Conclusion Managing pc-BPPV in one session is safe and reliable, resulting in fewer visits to outpatient clinics and optimization of treatment strategies.

Background: The definition and the behaviour of familial papillary thyroid cancer (FPTC) compared to the sporadic form (SPTC) are still debated. Some authors believe that only families with 3 or more affected members represent an actual example of familial diseases. Objectives: The objective of the study was to analyse the clinicopathological features and the outcome of sporadic and familial PTC patients also according to the number of affected members. Methods: Among 731 patients, we identified 101 (13.8%) with familial diseases, 79 with 2 affected members (FPTC-2) and 22 with 3 or more affected members (FPTC-3) followed for a mean period of 10 years. Results: FPTC patients had more frequently bilateral tumour (p = 0.007). No difference was found between the 2 groups for the other evaluated variables. At the time of the first follow-up (1–2 years after initial therapy), FPTC patients had a higher rate of persistent disease. However, at the last follow-up, the clinical outcome was not different between sporadic and familial patients. When the comparison between SPTC and FPTC was performed, according to the number of affected members, a significant trend between the 3 groups was observed for tumour diameter (p = 0.002) and bilaterality (p = 0.003), while we did not observe a significant trend for both response to initial therapy (p = 0.15) and last clinical outcome (p = 0.22). Conclusions: Our results suggest that, although the clinicopathological features of FPTC may be more aggressive, the long-term outcome is similar between FPTC and SPTC. A possible explanation is that PTC has a favourable prognosis, even when clinical presentation is more aggressive.

Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma.Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software.Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels.Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.

BACKGROUND Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). METHODS Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. FINDINGS With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p

(1) Background: Tumor recurrence after liver resection (LR) for intrahepatic cholangiocarcinoma (ICC) is common. Repeat liver resection (RLR) for recurrent ICC results in good survival outcomes in selected patients. The aim of this study was to investigate factors affecting the chance of resectability of recurrent ICC. (2) Methods: LR for ICC performed between January 2001 and December 2020 were retrospectively reviewed. Patients who had undergone first LR were considered for the study. Data on recurrences were analyzed. A logistic regression model was used for multivariable analysis of factors related to RLR rate. (3) Results: In total, 140 patients underwent LR for ICC. Major/extended hepatectomies were required in 105 (75%) cases. The 90-day mortality was 5.7%, Clavien–Dindo grade 3, 4 complications were 9.3%, N+ disease was observed in 32.5%, and the median OS was 38.3 months. Recurrence occurred in 91 patients (65%). The site of relapse was the liver in 53 patients (58.2%). RLR was performed in 21 (39.6%) patients. Factors that negatively affected RLR were time to recurrence ≤12 months (OR 7.4, 95% CI 1.68–33.16, p = 0.008) and major hepatectomy (OR 16.7, 95% CI 3.8–73.78, p &lt, 0.001) at first treatment. Survival after recurrence was better in patients who underwent RLR as compared with not resected patients (31 vs. 13.2 months, p = 0.02). (4) Conclusions: Patients with ICC treated at first resection with major hepatectomy and those who recurred in ≤12 months had significantly lower probability to receive a second resection for recurrence.

Single-procedure catheter ablation success rate is as low as 52% in atrial fibrillation (AF) patients. This study evaluated the feasibility of using clinical data and heart rate variability (HRV) features extracted from an implantable cardiac monitor (ICM) to predict recurrences in patients prior to undergoing catheter ablation for AF. HRV-derived features were extracted from the 500 beats preceding the AF onset and from the first 2 min of the last AF episode recorded by an ICM of 74 patients (67% male; 57 ± 12 years; 26% non-paroxysmal AF; 57% AF recurrence) before undergoing their first AF catheter ablation. Two types of classification algorithm were studied to predict AF recurrence: single classifiers including support vector machines, classification and regression trees, and K-nearest neighbor classifiers as well as ensemble classifiers. The sequential forward floating search algorithm was used to select the optimum feature set for each classification method. The optimum weighted voting method, which used an optimum combination of the single classifiers, was the best overall classifier (accuracy = 0.82, sensitivity = 0.76, and specificity = 0.87). Clinical and HRV features can be used to predict rhythm outcome using an ensemble classifier which would enable a more effective pre-ablation patient triage that could reduce the economic and personal burden of the procedure by increasing the success rate of first catheter ablation.

Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system has a significant role in the milieu predisposing to the triggers, perpetuators and substrate for atrial fibrillation. It has direct electrophysiological effects and causes alterations in atrial structure. In a significant portion of patients with atrial fibrillation, the autonomic nervous system activity is likely a composite of reflex excitation due to atrial fibrillation itself and contribution of concomitant risk factors such as hypertension, obesity and sleep-disordered breathing. We review the role of autonomic nervous system activation, with focus on changes in reflex control during atrial fibrillation and the role of combined sympatho-vagal activation for atrial fibrillation initiation, maintenance and progression. Finally, we discuss the potential impact of combined aggressive risk factor management as a strategy to modify the autonomic nervous system in patients with atrial fibrillation and to reverse the arrhythmogenic substrate. (c) 2018 Elsevier B.V. All rights reserved.

Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype.The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation.In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors.The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma Keywords: Vulvar carcinoma, Human papillomavirus, Recurrences, Metastases, Integration, Viral load

ObjectivesAdjuvant treatment of high-risk endometrial cancer (EC) is still controversial. Several studies have tried to clarify the best treatment strategy, and guidelines have been made, but no study to date has shown a survival benefit for radiation over chemotherapy. We aimed to evaluate the outcome of high-risk EC patients treated with adjuvant chemotherapy only in a population where the routine administration of adjuvant radiotherapy was omitted.MethodsThis is a retrospective study including 230 EC patients with International Federation of Gynecology and Obstetrics stage I type II, stage Ib type I/G3, stage II, and IIIc treated at Oslo University Hospital between 2005 and 2012. Standard treatment was hysterectomy, bilateral salpingo-oophorectomy and at least pelvic lymphadenectomy followed by adjuvant chemotherapy.ResultsOf the 230 high-risk patients, standard treatment was given to 146 patients (63.5%): 60 patients in stage I, 10 patients in stage II, and 76 patients in stage IIIc. Only 10% of patients with stage I disease relapsed, with 3.3% locoregional relapses and 6.7% distant relapses. Recurrence rate in stage IIIc was 39.5%, with 7.9% isolated vaginal and 31.6% distant relapses. The 3-year disease-free survival was 92% for stage I, 80% for stage II, and 60% for stage IIIc disease. In the total population, 55 patients had International Federation of Gynecology and Obstetrics stage Ia, 43 Ib, 42 stage II, and 90 stage IIIc disease. Recurrence rate in the total population was 29.6%, with 9.6% isolated vaginal recurrences, 1.7% recurrences located in the pelvis, and 18.3% distant recurrences.ConclusionsPatients with high-risk EC have acceptable vaginal/pelvic control rates after adjuvant chemotherapy. However, prognosis remains poor for patients with stage IIIc disease, also after chemotherapy.

Introduction Traditionally, follow‐up of colorectal cancer (CRC) is performed in secondary care. In new models of care, the screening part care could be replaced to primary care. We aimed to synthesise evidence on the diagnostic accuracy of commonly used screeners in CRC follow‐up applicable in primary care: carcinoembryonic antigen (CEA), ultrasound and physical examination. Methods Medline, EMBASE, Cochrane Trial Register and Web of Science databases were systematically searched. Studies were included if they provided sufficient data for a 2 × 2 contingency tables. QUADAS‐2 was used to assess methodological quality. We performed bivariate random effects meta‐analysis, generated a hypothetical cohort, and reported sensitivity and specificity. Results We included 12 studies (n = 3223, median recurrence rate 19.6%). Pooled estimates showed a sensitivity for CEA (≤ 5 μg/l) of 59% [47%–70%] and a specificity of 89% [80%–95%]. Only few studies reported sensitivities and specificities for ultrasound (36–70% and 97–100%, respectively) and clinical examination (23% and 27%, respectively). Conclusion In practice, GPs could perform CEA screening. Radiological examination in a hospital setting should remain part of the surveillance strategy. Personalised algorithms accounting for recurrence risk and changes of CEA‐values over time might add to the diagnostic value of CEA in primary care.

Objective: Atrial fibrillation is progressive disease with important health consequences, in which fibrosis is a key player. The aim of our study is to assess the effect of mineralcorticoid blockade on top of standard treatment in patients with atrial fibrillation after sinus rhythm restoration on the recurrence of the arrhythmia, hospitalizations and on the changes in levels of Galectin-3 as a marker of fibrosis. Methods: We prospectively studied 101 consecutive patients (56 females) at mean age 68.2 ± 7 with atrial fibrillation and sinus rhythm restoration, who were randomized on treatment with spironolactone on top of standard treatment or “usual care”. They were followed up for recurrences, hospitalization and death. The effect of spironolactone on safety was evaluated. Results: Recurrences of AF were detected in 64% of non-spironolactone group vs 57% in spironolactone group (p = 0.44). Spironolactone reduced the hospitalizations for AF, but it was not significant (p = 0.14). A Cox regression model showed only protective effect of spironolactone on AF hospitalizations, HR = 0.48, 95%CI = 0.2–1.15, р = 0.098. The same survival model for all-cause hospitalizations reached significance, with reduction of the events in the spironolactone group, HR- 0.44, 95% CI 0.2–0.94, р = 0.035. There was no difference regarding the composite endpoint (recurrences, all cause hospitalizations and death). Treatment with spironolactone did not influence the Gal-3 levels. Treatment with spironolactone has not influenced significantly the levels of serum potassium and creatinine. Conclusion: Treatment with spironolactone has protective effect regarding hospitalization for atrial fibrillation and significantly reduces all cause hospitalizations. It does not influence the biomarker of fibrosis Gal-3 after one-year treatment. The use of spironolactone in patients with AF is safe, but regular follow up is needed and recommended. Further studies are necessary, to clarify the potential of spironolactone to improve the AF prognosis.

Background Surgical wound infection contributes to prolonged recovery time after pilonidal sinus excision. As a standard procedure after surgery, we recommend our patients to perform water irrigations in the intergluteal cleft 4 to 6 times a day during the post-operative period. Our hypothesis is that this should reduce healing time and complication rates. The aim of this study was to measure the importance of sacro coccygeal hygiene in the management of pilonidal sinus disease. Methods We retrospectively collected data after surgical management of pilonidal sinus (sinusectomy procedures) in our division over a 10-year period. Patients were divided into three groups according to their local hygiene during postoperative follow-up and scored one (G1: good hygiene) to three (G3: poor hygiene). Primary outcome was complication rates. Secondary endpoints were, healing time, follow-up, time off work, and recurrence rate. Results In G1 (N = 112), complication rate was 3.6%. In G2 (N = 109), it was 5.5%, whereas in G3 (N = 71), it reached 7.03%. However, there were no statistically significant differences between hygiene groups regarding complication rates in both univariate and multivariable analysis. Regarding secondary outcomes, there were significant differences between hygiene groups concerning median follow-up (p = 0.0001) and median time off work (p = 0.0127). Conclusion Good hygiene of wound is essential for optimal, rapid healing without complications. The importance of this report is to show that thanks to our hygiene follow-up strategy with frequent perineal irrigations and regular follow-up checks, patients with at a first glance “unclean local conditions”, reached similar complications, median healing time and recurrences rates to patients with medium and good wound hygiene level.

Background The prognostic significance of concomitant superficial vein thrombosis (SVT) in patients with lower-limb deep vein thrombosis (DVT) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the rates of subsequent pulmonary embolism (PE), recurrent DVT, major bleeding or death in patients with lower-limb DVT, according to the presence or absence of concomitant SVT. Results From March 2015 to May 2020, there were 8,743 patients with lower-limb DVT. Of these, 745 (8.5%) had concomitant SVT. Most patients (97.4% in both subgroups) received anticoagulant therapy (median duration: 138 vs. 147 days). During follow-up (median: 193 vs. 210 days), 156 (1.8%) patients developed subsequent PE, 336 (3.8%) had recurrent DVT, 201 (2.3%) had major bleeding and 844 (9.7%) died. Patients with concomitant SVT had a higher rate of subsequent PE (rate ratio [RR]: 2.11; 95% confidence interval [95%CI]: 1.33–3.24) than those with isolated DVT, with no significant differences in the rates of recurrent DVT (RR: 0.80; 95%CI: 0.50–1.21), major bleeding (RR: 0.77; 95%CI: 0.41–1.33) or death (RR: 0.81; 95%CI: 0.61–1.06). On multivariable analysis, patients with DVT and SVT concomitantly were at increased risk of subsequent PE during anticoagulation (adjusted hazard ratio [HR]: 2.23; 95%CI: 1.22–4.05) and also during the entire follow-up period (adjusted HR: 2.33; 95%CI: 1.49–3.66). Conclusion Patients with lower-limb DVT and SVT concomitantly are at increased risk of developing PE. Further studies are needed to externally validate our findings and to determine if these patients could benefit from a different management strategy.

Background Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. Methods This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2-25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play-performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m(2) per day, capped at 24 mg per day, and etoposide (100 mg/m(2) per day) plus ifosfamide (3000 mg/m(2) per day) were administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. Findings 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B were ineligible for enrolment in the study. In phase 1, dose-limiting toxicities were observed in three patients (one in the lenvatinib 11 mg/m(2) combination group and two in the 14 mg/m2 combination group) and the recommended phase 2 dose was determined as lenvatinib 14 mg/m(2) per day (with daily dose cap of 24 mg) and etoposide 100 mg/m(2) per day plus ifosfamide 3000 mg/m2 per day administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. 35 patients from phase 1 (cohort 3A; n=15) and phase 2 (cohort 3B; n=20) were treated at the recommended phase 2 dose and their results were pooled. Progression-free survival at 4 months was 51% (95% CI 34-69) in 18 of 35 patients per the binomial estimate. The most common grade 3-4 treatment-emergent adverse events were neutropenia (27 [77%] of 35), thrombocytopenia (25 [71%]), anaemia (19 [54%]), and decreased white blood cell count (19 [54%]). 26 [74%] of 35 patients had serious treatment-emergent adverse events and no treatment-related deaths occurred. Interpretation Lenvatinib with etoposide plus ifosfamide shows promising antitumour activity with no new safety signals in patients with refractory and relapsed osteosarcoma. These findings warrant further investigation in an ongoing randomised phase 2 study (NCT04154189). Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. Evidence acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990–2018) as concerns the years of the publication was considered. Evidence synthesis: Primary disease: the median 5-year LC was 43.5% (range 19–68%); the median 5-year DFS was 44.5% (range 44–81%); the median 5-year OS was 50.5% (range 27–85%). Recurrent disease: the median 5-year DFS was 64% (range 56–72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3–4) ranged from 0% to 14.3% (median 7.7%). Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Objective The present study analyzed long-term outcomes and complications of laparoscopic lateral suspension (LLS) with mesh to treat apical and anterior pelvic organ prolapse (POP). Study design A prospective cohort study on 125 patients with vaginal bulge and apical +/− anterior prolapse scheduled for LLS who consecutively underwent LLS between April 2013 and January 2017 in Gynecologic Department of Santa Chiara Hospital in Trento and University of Pisa. The main outcome measure was anatomic and symptomatic POP outcome; the secondary outcomes measures were recurrence, reoperation rate, de novo posterior POP and complications. Percentage distribution of the pre- and postoperative POP-Q stages was compared at mean follow-up. Wilcoxon signed rank sum test was used to compare preoperative POP-Q stage and postoperative POP-Q stage ate mean follow up, for each patient (paired data) and for each type of prolapse. Results 120 patients were included in the study. At 2 years 89 % of patients were asymptomatic and anatomic success rate was 94.2 % for the anterior compartment, 94.9 % for the apical compartment. Concerning posterior compartment prolapse 2 (1.7 %) patients referred stage 3 de novo prolapse during follow-up. The complication rate of Clavien-Dindo >3 was 0,8 %. Repeat surgery for POP occurred in 6.4 % of cases. The appearance of POP-Q recurrences was concentrated at 6 months follow-up. BMI > 25 was correlated with de novo posterior compartment appearance during follow-up. Conclusions LLS for the treatment of apical and anterior POP is a technique with optimal results in term of safety and effectiveness after 2 years follow-up.

Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare form of soft tissue sarcoma. It is characterized by a slow evolution, with local recurrences and late metastases that are mainly pulmonary and pleural in about 50% of cases. The treatment is based on the surgery which must be as wide as possible. The efficacy of adjuvant therapy in the control of SEF is not yet demonstrated. Chemotherapy is used in recurrences, some have also proposed radiotherapy. Long-term follow-up of patients with SEF is therefore essential.

Objective To evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy. Methods The cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005–2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates. Results Uterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1–2

The objective of the study is to present the clinico-pathological features of cystic and classic adenomatoid odontogenic tumors (AOTs) in order to identify the differences between the two variants of AOT. Materials and method: The study sample comprised of 41 AOTs, which were categorized into cystic and classic AOTs. Cystic AOTs are diagnosed as such when macroscopic and microscopic evidence of a cyst is present together with histopathological criteria of AOT (WHO&ndash, 2017). Results: The study sample comprised of eleven cystic and thirty classic AOTs. Eight cystic AOTs were regarded as arising from dentigerous cysts as these lesions were attached to the cemento-enamel junction of the impacted teeth. Though not statistically significant, in contrast to classic AOTs which showed female predilection, cystic AOTs were more prevalent in males. Cystic AOTs tend to present as significantly larger lesions compared to classic AOTs (p &lt, 0.02). In both cystic and classic AOTs, duct-like structures and epithelial whorls were the two most prominent histopathological features present in the majority of tumors. Two AOTs with massive amounts of dentinoid occurred in the mandible and presented as large lesions that eroded cortical bone. None of the 12 patients with follow-up information presented with recurrences. Conclusion: Except for the size of the lesion, no significant clinico-pathological differences were observed between cystic and classic AOTs. Therefore the cystic AOTs can be considered as a variant of AOT with enucleation, simple excision, or radical excision as the treatment of choice depending on the extent of the lesion, similar to classic AOTs.

Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

Objective: This article describes a case of an Oral Eosinophilic Ulcer (OEU) in an otherwise healthy 31-year-old white woman. Introduction: The importance of reporting this case was the presence of recurrent episodes with lesions appearing in different areas of the oral mucosa, a type of manifestation not commonly associated with this disease. A typical manifestation of OEU occurs as a single ulceration that goes into healing after an incisional biopsy, a procedure usually required for a proper diagnosis of the disease. In spite of trauma being suggested as the main culprit of OEU, the exact pathogenesis mechanism of this disease remains controversial. Case report: The pattern of the present case contradicts the usually common course of the disease, as the patient had experienced many recurrent episodes for almost 2.5 years, with the recurrences occurring even after biopsies performed during some of the relapses. Differential diagnosis included recurrent aphthous stomatitis, recurrent intra-oral herpes, autoimmune disease, Crohn’s disease and malignancy. Conclusion: Fortunately, the patient has been free of any recurrences for 1.5 years since the last biopsy was taken at the time she came to our clinic seeking treatment.

Background: Complete resection is the mainstay of treatment for thymoma, but few studies have investigated the extent of resection on normal thymus. Extended thymectomy is considered the treatment of choice for myasthenic patients with thymoma, while the optimal therapy for non-myasthenic patients is still a matter of debate. The aim of this retrospective study was to compare extended thymectomy vs. thymomectomy in non-myasthenic thymoma patients for (I) oncological outcome, (II) multicentric thymoma occurrence and (III) postoperative myasthenia gravis (MG) development. Methods: A retrospective comparative study was conducted on 92 non-myasthenic patients with completely resected thymoma, according to the extent of resection: extended thymectomy (70 patients) vs. R0-mediastinal thymomectomy (22 patients). Clinical and pathological characteristics, oncological outcome and postoperative MG occurrence were compared between the two study groups. Results: We did not observe any significant differences in gender, age, symptomology, preoperative chemotherapy, histology, tumour size, adjuvant therapy or complications. There were no recorded postoperative mortalities. Stage distribution was different between the two groups: similar percentages of early stage thymoma for both groups were present, but there was a prevalence of stage III for extended thymectomy and stage IV for thymomectomy (P < 0.01). At a median follow-up of 77.4 months (range 1-255 months), no statistically significant differences were recorded in local recurrence (P=0.396), thymoma related deaths (P=0.504), multicentric thymoma occurrence (P=0.742) and postoperative MG development (P=0.343). A high preoperative anti-acetylcholine receptor antibodies (ARAb) serum titer assay was statistically correlated with postoperative MG occurrence (r=0.49, P < 0.05). Conclusions: Thymomectomy appears to be a valid treatment option for non-myasthenic thymoma patients, as this procedure was associated to the same 5-year oncological results, compared to extended thymectomy, for both stage I-II small thymomas and patients with giant unilateral masses, as well as advanced diseases. Moreover, thymomectomy was not associated to an increased rate of postoperative MG.

// Flavio Fazioli 1, * , Gianluca Colella 2, * , Roberta Miceli 3 , Mariano Giuseppe Di Salvatore 1 , Michele Gallo 1 , Serena Boccella 4 , Annarosaria De Chiara 5 , Carlo Ruosi 2, * and Filomena de Nigris 6, * 1 Division of Musculoskeletal Oncology Surgery, National Cancer Institute G. Pascale, Naples, Italy 2 Department of Human Health, Federico II University of Naples, Naples, Italy 3 S.C. Cellular Biology and Biotherapy, National Cancer Institute G. Pascale, Naples, Italy 4 Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples Italy 5 Division of Pathology, National Cancer Institute G. Pascale Foundation, Naples, Italy 6 Department of Biochemistry, Biophysics and General Pathology, University of Campania “Luigi Vanvitelli”, Naples Italy * These authors have contributed equally to this work Correspondence to: Filomena de Nigris, email: Filomena.denigris@unina2.it Keywords: recurrences, sarcoma, angiogenesis, stem cells, AKT Received: March 31, 2017 Accepted: May 29, 2017 Published: June 28, 2017 ABSTRACT Giant cell tumors of bone (GCTB) are rare sarcomas with a high rate of unpredictable local relapse. Studies suggest that surgical methods affect recurrence, supporting the idea that local disease develops from re-growth of residual cancer cells. To identify early prognostic markers of individual risk of recurrence, we evaluated the effect of post-surgery fluids from a cohort of GCTB patients on growth of primary and established sarcoma cell lines, and mice xenograph. Post-surgery fluids increased cell growth and enhanced expression of CD44 ++ , the principal receptor for the extracellular matrix component hyaluronan and the mesenchymal stem marker CD117 + . Cancer cells became highly invasive and tumorigenic, acquiring stemness properties, and activated AKT/mTOR pathway. Prolonged stimulation with post-surgery fluids down-regulated the mesenchymal gene TWIST1 and Vimentin protein, and transdifferentiated cells into tubule-like structures positive to the endothelial markers VE-Cadherin and CD31 + . In mice, post-surgery fluids gave rise to larger and more vascularized tumors than control, while in patients AKT/mTOR pathway activation was associated with recurrence by logistic regression (Kaplan-Meier; P

Background: Warts are mucocutaneous infections caused by human papillomavirus (HPV). Of the various modalities of treatment currently available, no single modality is uniformly efficacious and recurrences are common. Homologous autoimplantation is a minimally invasive procedure, which treats warts by stimulating a specific immune response against HPV. Aim: The aim of the study was to evaluate the clinical outcomes and recurrences after a single sitting of homologous autoimplantation therapy for multiple nonvenereal warts. Materials and Methods: Single homologous autoimplantation of wart tissue was done in 75 patients of multiple facial, palmoplantar, or common warts, reporting to a tertiary care dermatology center. They were assessed at 3 months for the outcome of the procedure, and those with complete clearance were followed up for 1 year for any recurrences. Results: Complete clearance was observed in 30 (40%) of the cases and 10 (13.3%) cases showed moderate clearance. In 13 (17.3%) cases, there was mild clearance, whereas 22 (29.3%) patients did not show any response to treatment. Patients with facial warts showed good therapeutic response with complete clearance seen in 62.5%, compared to plantar warts, where complete clearance was achieved only in 16%. At the end of the study period, recurrence was seen in only 1 (3.33%) patient in the complete clearance group. Conclusion: Autoimplantation therapy as a one time minimally invasive procedure has moderate efficacy in treating multiple warts with the best outcome being for facial warts. The virus-specific immunity generated in the process reduces the chances of recurrences.

SummaryEven though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1–2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99–7.63), 11.2 (95 %CI: 9.91–12.7) and 19.4 (95 %CI: 15.4–24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13–6.56), 10.3 (95 %CI: 9.02–11.7) and 19.4 (95 %CI: 15.4–24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8–28.0), 58.5 (95 %CI: 55.5–61.7) and 120 (95 %CI: 110–131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50–0.56) for recurrent VTE, 0.56 (95 %CI: 0.54–0.59) for major bleeding and 0.54 (95 %CI: 0.52–0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.

Background Evidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80 months. Methods Based on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity — number of affective episodes, time spent ill, and cycle length — were recorded and compared between each half of the follow-up period. Results On average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. Conclusions The results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them. Fil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Samame, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Marengo, E.. Universidad Favaloro; Argentina Fil: Igoa, A.. Universidad Favaloro; Argentina Fil: Scápola, M.. Universidad Favaloro; Argentina Fil: Strejilevich, S. A.. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina

Introduction: Prediction models using logistic regression may perform poorly in external patient cohorts. However, there is a need to standardize and validate models for clinical use. The purpose of this project was to describe a method for validation of external NTCP models used for patient selection in the randomized trial of protons versus photons in head and neck cancer radiotherapy, DAHANCA 35. Material and methods: Organs at risk of 588 patients treated primarily with IMRT in the randomized controlled DAHANCA19 trial were retrospectively contoured according to recent international recommendations. Dose metrics were extracted using MatLab and all clinical parameters were retrieved from the DAHANCA database. The model proposed by Christianen et al. to predict physician-rated dysphagia was validated through the closed testing, where change of the model intercept, slope and individual beta’s were tested for significant prediction improvements. Results: Six months prevalence of dysphagia in the validation cohort was 33%. The closed testing procedure for physician-rated dysphagia showed that the Christianen et al. model needed an intercept refitting for the best match for the Danish patients. The intercept update increased the risk of dysphagia for the validation cohort by 7.9 ± 2.5% point. For the raw model performance, the Brier score (mean squared residual) was 0.467, which improved significantly with a new intercept to 0.415. Conclusions: The previously published Dutch dysphagia model needed an intercept update to match the Danish patient cohort. The implementation of a closed testing procedure on the current validation cohort allows quick and efficient validation of external NTCP models for patient selection in the future.

Objective: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. Methods: This national cohort study (2005–2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. Results: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. Conclusion: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.

In primary conjunctival melanoma (CoM), one of the characteristics that is associated with an increased risk of metastases and death is a lack of tumour pigmentation. The aim of this study was to investigate whether the degree of pigmentation of CoM recurrences relates similarly to clinical outcome. A data set of 177 patients with a CoM recurrence from the Wills Eye Hospital (USA) and the Leiden University Medical Center (The Netherlands) was analysed. The relation between clinical tumour pigmentation of the recurrences, the characteristics of the primary lesions and clinical outcome was investigated. In 117 (66%) of 177 patients with a CoM recurrence, tumour pigmentation was known: 71 patients (61%) had recurrences with low pigmentation. Primary lesions had low pigmentation in 39% of cases, which is significantly different (p = 0.001). However, low tumour pigmentation of recurrences correlated with low tumour pigmentation of the primary lesion (p

Background Papillary thyroid microcarcinoma is a subtype of thyroid cancer that may be managed with active surveillance rather than immediate surgery. Active surveillance decreases complication rates and may decrease health care costs. This study aims to analyze complication rates of thyroid surgery, papillary thyroid microcarcinoma recurrence, and survival rates. Additionally, the costs of surgery versus hypothetic active surveillance for papillary thyroid microcarcinoma are compared in an Australian cohort. Methods Papillary thyroid microcarcinoma patients were included from a prospectively collected surgical cohort of patients treated for papillary thyroid cancer between 1985 and 2017. The primary outcomes were the complications of thyroid surgery, recurrence-free survival, overall survival, and cost of surgical treatment and active surveillance. Results In a total of 349 patients with papillary microcarcinoma with a median age of 48 years (range, 18–90 years), the permanent operative complications rate was 3.7%. Postoperative radioactive iodine did not decrease recurrence-free survival (P = .3). The total cost of surgical treatment was $10,226 Australian dollars, whereas hypothetic active surveillance was at a yearly cost of $756 Australian dollars. Estimated cost of surgical papillary thyroid microcarcinoma treatment was equivalent to the cost of 16.2 years of active surveillance. Conclusion Surgery may have a long-term economic advantage for younger Australian patients with papillary thyroid microcarcinoma who are likely to require more than 16.2 years of follow-up in an active surveillance scheme.

Background: Due to the frequency and severity of cold symptoms in children, and the risk of associated complications, effective treatments are urgently needed. Here we evaluated the safety profile and treatment benefits of Echinacea in children with acute cold and flu symptoms. Methods: A total of 79 children (4–12 years) were randomized to a treatment regimen of three or five times daily Echinaforce Junior tablets (total of 1200 or 2000 mg Echinacea extract, EFJ) for the prospective treatment of upcoming cold and flu episodes at first signs. Parents recorded respiratory symptoms daily during episodes in their child and physicians and parents subjectively rated tolerability. Results: EFJ was used to treat 130 cold episodes in 68 children and was very well tolerated by more than 96% positive physician’s ratings. EFJ-treated cold episodes lasted 7.5 days on average, with nine out of 10 episodes being fully resolved after 10 days. Five EFJ tablets daily reduced the average episode duration by up to 1.7 days (p < 0.02) in comparison to three EFJ tablets daily regimen. Effective symptom resolution finally contributed to a low antibiotic prescription rate in this study of 4.6%. Conclusions: EFJ tablets present a valuable option for the treatment of acute cold episodes in children showing a wide safety margin and increased therapeutic benefits at five tablets daily.

The paper highlights main areas in the development of European oncology care to patients with malignant ovarian neoplasms. It discusses the major issues considered at the 5th Annual Meeting of Oncologists on Arrangement of Anticancer Therapy into the Era of Personalized Therapy hosted by the MD Anderson Cancer Center.

Gingival growths are one of the frequently encountered types of lesion in the oral cavity. It is the common site for neoplastic and nonneoplastic lesions. Peripheral ossifying fibroma (POF) is one of the inflammatory reactive hyperplasias of the gingiva. It represents a separate clinical entity with diverse histopathological features. Even after adequate surgical excision of the lesion, repeated recurrence is not uncommon. Studies show a recurrence rate of 16-20% in these lesions. The suggested etiology for POF is low-grade irritation due to plaque and calculus. Proper excision of such overgrowths and appropriate oral hygiene instructions will ensure that the lesion does not recur. This case report is of a large, solitary gingival swelling in the maxilla of a 36-year-old male patient that had recurred for the third time after the surgical excision.

Background and Objectives: Psoriasis is a chronic, papulosquamous disorder of the skin with variable morphology, characterized by periods of remission and reactivity. Psoriasis is less common in the tropics and in dark-skinned persons. Prevalence in West Africans has been noted to be similar to that of the African-Americans suggesting a similarity in genetic ancestry. This study aimed to describe the clinical characteristics of psoriasis and precipitating factors in Nigerian patients. Materials and Methods: This is a retrospective study of all dermatology patients with features of psoriasis who attended the dermatology outpatient clinic of the hospital between January 2007 and May 2012. Data were obtained from the patients' clinic notes and protocol for psoriasis, which documented patients' demographic data, clinical presentations, and precipitating factors. Results: Psoriasis was found in 1.13% (124/11,015) of the study population. There was a male preponderance with a male to female ratio of 1.34:1. The majority of patients seen were in the fourth decade of life. Stress, alcohol, and drugs were the most reported predisposing factors to psoriasis. All types of psoriasis were found, and plaque psoriasis was the most common. Conclusion: This study confirms the increasing frequency of psoriasis among dermatology patients in Nigeria, which may either be due to an increased proficiency in diagnosing the condition by physicians or increase prevalence of environmental factors. The current trend in the management of psoriasis is focused on treating the inflammatory process as well as managing the modifiable environmental triggers.

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (

Current guidelines recommend to prolong anticoagulant treatment in patients with cancer with venous thromboembolism (VTE); only few studies evaluated other parameters than cancer itself for selecting patients at higher risk of recurrent VTE. Long-term management of VTE is thus challenged by several controversies mainly for patients compliance. We here report results of a long-term follow-up in patients with deep vein thrombosis under anticoagulant treatment with low-molecular-weight heparin (LMWH) for residual vein thrombosis (RVT) detected at compression ultrasonography (CUS), 6 months after standard anticoagulant treatment. Patients with RVT were deemed at high risk of recurrences and included in the current observational study. They continued LMWH (reduced at 75% standard dose) for further additional 2 years after enrolment or until death. Patients were followed up every 3 months or earlier, if needed. Among ancillary study end points, there was the assessment of patients’ quality of life during daily treatment with subcutaneous injections. Quality of life was determined by the EORTC-C30 questionnaire, administered by a skilled psychologist at enrolment and every 6 months follow-up visits. Overall, 128 patients were evaluated during follow-up. Mean global EORTC-C30 score at enrollment and at 6, 12 and 24 months follow-up were 52.1, 51.4, 50.8 and 50.1, respectively. There were no statistically significant differences between scores at enrolment and at the last available follow-up (P = .1). Long-term treatment with LMWH resulted, effective and safe, it was globally well tolerated and exempt of negative impact on quality of life of the enrolled patients. Reported results support long-term anticoagulant treatment with LMWH in cancer patients at risk of recurrent VTE.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults. Catheter ablation (CA) is one of the most important management strategies to reduce AF burden and AF-associated complications. In order to stratify the risk of adverse events and to predict treatment success in AF patients undergoing CA, several risk stratification scores had been developed during the last decade. The aim of this review is to provide an overview of the most important clinical risk scores predicting rhythm outcomes, electro-anatomical substrate and mortality in AF.

ObjectiveEndometrial cancer (EC) recurrences are relatively common with no standardized way of describing them. We propose a new classification for them called locoregional, nodal, metastasis, carcinomatosis recurrences (rLMNC).Patients and MethodsThe data of 1230 women with EC who were initially treated by primary surgery were included in this French multicenter retrospective study. Recurrences were classified based on dissemination pathways: (1) locoregional recurrence (rL); (2) nodal recurrence (rN) for lymphatic pathway; (3) distant organ recurrence (rM) for hematogenous pathway; and (4) carcinomatosis recurrence (rC) for peritoneal pathway. These pathways were further divided into subgroups. We compared recurrence free survival and overall survival (OS) between the 4 groups (rL/rN/rM/rC).ResultsThe median follow-up was 35.6 months (range, 1.70–167.60). One hundred ninety-eight women (18.2%) experienced a recurrence: 150 (75.8%) experienced a single-pathway recurrence and 48 (24.2%) a multiple-pathway recurrence. The 5-year OS was 34.1% (95% confidence interval [CI], 27.02%–43.1%), and the median time to first recurrence was 18.9 months (range, 0–152 months). The median survival after recurrence was 14.8 months (95% CI, 11.7–18.8). Among women with single pathway of recurrence, a difference in 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) was found between the 4 rLNMC groups. The carcinomatosis group had the worst prognosis compared with other single recurrence pathways. Women with multiple recurrences had poorer 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) than those with single metastasis recurrence, other than women with peritoneal carcinomatosis.ConclusionsThis easy-to-use and intuitive classification may be helpful to define EC recurrence risk groups and develop guidelines for the management of recurrence. Its prognosis value could also be a tool to select homogenous populations for further trials.

Background In addition to tumor characteristics and lifestyle factors, cancer relapses are often related to the risk of death but have not been jointly studied. We investigate the prognostic factors of recurrent events and death after a diagnosis of breast cancer and predict individual deaths including a history of recurrences. Methods The E3N (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l’Education Nationale) study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. Overall survival and three types of recurrent events were considered: locoregional recurrence, metastasis, and second primary breast cancer. Recurrent events and death were analyzed using a joint frailty model. Results The analysis included 4926 women from the E3N cohort diagnosed with a first primary invasive breast cancer between June 1990 and June 2008; during the follow-up, 1334 cases had a recurrence (median time of follow-up is 7.2 years) and 469 women died. Cases with high grade, large tumor size, axillary nodal involvement, and negative estrogen and progesterone receptors had a higher risk of recurrence or death. Furthermore, smoking increased the risk of relapse. For cases with a medium risk profile in terms of tumor characteristics and lifestyle factors, the probability of dying between 5 and 10 years after diagnosis was 6, 20 and 36% for 0, 1 or 2 recurrences within the first 5 years after diagnosis, respectively. Conclusions Our study showed the importance of considering baseline lifestyle characteristics and history of relapses to dynamically predict the risk of death in breast cancer cases. Medical experience coupled with an estimate of a patient’s survival probability that considers all available information for this patient would enable physicians to make better informed decisions regarding their actions and thus improve clinical output. Electronic supplementary material The online version of this article (10.1186/s12885-018-4076-4) contains supplementary material, which is available to authorized users.

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.

BACKGROUND: In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT. PATIENTS AND METHODS: One hundred seventy-two patients, T1c to T3 and N0 (clinically and according to ultrasound) candidates for NAT were included. We compared the outcomes of 2 groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT (post-NAT) from May 2014 to July 2016. RESULTS: Both groups were homogeneous in baseline patient characteristics. The SLNB was positive in 50 patients [41.7%] (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%] (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%] versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3-9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group were no recurrences after a median follow-up of 16 months. Finally, SLNB after NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and the identification of the SLNB was in 122 patients [100%] versus 49 patients [98%]. CONCLUSION: SLNB performed after NAT significantly reduces the rate of lymphadenectomies without any increase in recurrences at early follow-up. Furthermore, it allows systemic treatment to be started earlier without interfering in the SLNB identification rate.

Introduction Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. Methods We used the RIETE (Registro Informatizado Enfermedad Trombo Embolica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. Results In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71–5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47–2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14–8.17) and anaemia (HR: 4.11; 95%CI: 1.45–11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68–10.1) were associated with at increased risk for major bleeding. Conclusions The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy.

ResumenAntecedentesDesde la introducción de la biopsia selectiva del ganglio centinela, su utilización en pacientes con melanoma cutáneo y ganglios clínicamente negativos permanece controvertido. Hemos evaluado nuestra experiencia en biopsia selectiva del ganglio centinela en pacientes con melanoma.Material y métodosEstudio retrospectivo observacional, en el que hemos estudiado una muestra de 69 pacientes diagnosticados de melanoma cutáneo primario sin evidencia clínica de afectación metastásica, a los que se realizó biopsia selectiva del ganglio centinela desde octubre de 2005 hasta diciembre de 2013. El ganglio centinela fue identificado mediante una linfogammagrafía preoperatoria y posterior detección intraoperatoria con sonda gammadetectora.ResultadosLa tasa de identificación del ganglio centinela fue del 98.5%. El ganglio centinela fue positivo en 23 pacientes (33.8%). Las complicaciones postoperatorias después de la biopsia selectiva del ganglio centinela fueron observadas en el 4.4%, frente al 38% de los pacientes sometidos a linfadenectomía.ConclusiónLa biopsia selectiva del ganglio centinela en pacientes con melanoma proporciona valiosa información sobre las vías de diseminación linfática del tumor, y también permite una aproximación a la estadificación regional del mismo, evitando los efectos secundarios de la linfadenectomía. No obstante, serían necesarios estudios de mayor tamaño muestral y tiempo de seguimiento para confirmar la validez de la técnica de la biopsia selectiva del ganglio centinela en pacientes con melanoma, y especialmente de la linfadenectomía en casos de ganglio centinela positivo.AbstractBackgroundSince the introduction of sentinel lymph node biopsy, its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. Our experience of sentinel lymph node biopsy for melanoma is presented and evaluated.Material and methodsA cohort study was conducted on 69 patients with a primary cutaneous melanoma and with no clinical evidence of metastasis, who had sentinel lymph node biopsy from October-2005 to December-2013. Sentinel lymph node biopsy was identified using preoperative lymphoscintigraphy and subsequent intraoperative detection with gamma probe.ResultsThe sentinel lymph node biopsy identification rate was 98.5%. The sentinel lymph node biopsy was positive for metastases in 23 patients (33.8%). Postoperative complications after sentinel lymph node biopsy were observed in 4.4% compared to 38% of complications in patients who had complete lymphadenectomy.ConclusionThe sentinel lymph node biopsy in melanoma offers useful information about the lymphatic dissemination of melanoma and allows an approximation to the regional staging, sparing the secondary effects of lymphadenectomy. More studies with larger number of patients and long term follow-up will be necessary to confirm the validity of sentinel lymph node biopsy in melanoma patients, and especially of lymphadenectomy in patients with positive sentinel lymph node biopsy.

Background Since the introduction of sentinel lymph node biopsy, its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. Our experience of sentinel lymph node biopsy for melanoma is presented and evaluated. Material and methods A cohort study was conducted on 69 patients with a primary cutaneous melanoma and with no clinical evidence of metastasis, who had sentinel lymph node biopsy from October-2005 to December-2013. Sentinel lymph node biopsy was identified using preoperative lymphoscintigraphy and subsequent intraoperative detection with gamma probe. Results The sentinel lymph node biopsy identification rate was 98.5%. The sentinel lymph node biopsy was positive for metastases in 23 patients (33.8%). Postoperative complications after sentinel lymph node biopsy were observed in 4.4% compared to 38% of complications in patients who had complete lymphadenectomy. Conclusion The sentinel lymph node biopsy in melanoma offers useful information about the lymphatic dissemination of melanoma and allows an approximation to the regional staging, sparing the secondary effects of lymphadenectomy. More studies with larger number of patients and long term follow-up will be necessary to confirm the validity of sentinel lymph node biopsy in melanoma patients, and especially of lymphadenectomy in patients with positive sentinel lymph node biopsy.