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Background: Our systematic review aimed to critically evaluate empirical literature describing the association of muscle-strengthening exercise (MSE) with recurrence and/or mortality among breast cancer survivors., Methods: We included English-language empirical research studies examining the association between MSE and recurrence and/or mortality among females diagnosed with breast cancer. Seven databases (MEDLINE, PsycINFO, Embase, Scopus, Web of Science, Cochrane CENTRAL, and CINAHL) were searched in September 2023. Quality was appraised using the Mixed Methods Appraisal Tool. Results are summarized descriptively., Results: Five sources were identified. MSE measurement differed in relation to the description of the MSE (i.e., muscle-strengthening vs. strength training), examples of activities (e.g., sit-ups or push-ups vs. calisthenics vs. circuit training), and exercise frequency (i.e., days vs. times/week). Findings offer provisional evidence that some MSE may lower the hazards of recurrence and mortality. This association may vary by race, weight status, and menopausal status., Conclusions: In summary, limited available evidence suggests that MSE may lower the hazards of recurrence and mortality. More consistent measurement and analyses would help generate findings that are more readily comparable and applicable to inform clinical practice. Further research is needed to improve understanding of the strength and differences of these associations among underserved and underrepresented women., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: Hepatoblastoma is the most common pediatric liver malignant neoplasm, and accurate risk stratification is essential for guiding treatment., Objective: To validate the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) in an independent cohort of patients with hepatoblastoma and evaluate the association of pretreatment hepatoblastoma histological subtype with prognosis., Design, Setting, and Participants: This is a single-institution retrospective cohort study of 96 pediatric patients with hepatoblastoma diagnosed and treated between June 1, 2000, and December 31, 2016, with recent therapy and independent of the CHIC-HS discovery cohort. Each patient was assigned a risk group according to CHIC-HS. The histological characteristics of each tumor were assessed based on the International Pediatric Liver Tumor Consensus Classification. Data were analyzed from May 2018 to May 2019., Main Outcomes and Measures: The main outcomes were event-free survival (EFS) and overall survival (OS). Cox regression analysis was used to examine the associations of patient characteristics and tumor histological characteristics with survival., Results: A total of 96 patients (median [range] age, 1.9 [0.4-18] years; 36 [38%] girls and 60 [63%] boys) were assessed, including 15 with very low risk, 28 with low risk, 23 with intermediate risk, and 30 with high risk, according to CHIC-HS criteria. There were a total of 13 cancer-related deaths; median (range) follow-up was 3.5 (0.1-17.8) years for those alive at the last follow-up. The estimated 5-year OS rates were 100% in the very low-risk group, 94.7% (95% CI, 68.1%-99.2%) in the low-risk group, 89.2% (95% CI, 63.1%-97.2%) in the intermediate-risk group, and 57.9% (95% CI, 34.6%-75.5%) in the high-risk group. In a multivariable analysis, we confirmed that CHIC-HS significantly estimated EFS (high-risk group vs very low- and low-risk groups: hazard ratio [HR], 45.59; 95% CI, 9.39-209.5; P < .001) and OS (high-risk group vs very low- and low-risk groups: HR, 21.95; 95% CI, 2.76-174.29; P < .001). In the subcohort of 84 patients for whom pretreatment tumor histological data were available, tumor epithelial histological subtypes were found to be significantly associated with both EFS and OS. Patients in the CHIC-HS high-risk group and with embryonal-only histological subtype had the highest risk of relapse or disease progression (high-risk: HR, 42.62; 95% CI, 9.91-203.9; embryonal: HR, 3.28; 95% CI, 1.21-8.9) and death (high-risk: HR, 18.78; 95% CI, 2.31-152.84; embryonal: HR, 7.12; 95% CI, 1.51-33.52)., Conclusions and Relevance: This cohort study found that CHIC-HS performed as expected in an independent cohort that was more recently treated. Incorporation of pretreatment tumor histological data into CHIC-HS may provide additional prognostic value.

Background: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS., Methods: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS., Results: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%., Conclusions: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Abu-Rustum reports grants from Stryker/Novadaq and GRAIL (paid to the institution). The remaining authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The prognostic value of a low skeletal mass index (SMI) has been investigated in locally advanced oesophageal (LAE) cancer at diagnosis. However, nothing is known about its evolution and clinical impact between initial diagnosis and recurrence., Methods: A total of 89 patients treated for LAE cancer between January 2009 and December 2019 were included in this study. Computed tomography (CT) scans before treatment and at recurrence were evaluated. SMI and other body composition parameters were analysed by the L3 scan method., Results: Participants were aged 66.0 (36.0-86) years. The incidence of low SMI increased by 12.3% between diagnosis and recurrence (70.7% vs. 83.0%, respectively) over a median follow-up of 16.9 (1.7-101.6) months. Patients with high SMI at diagnosis showed loss of muscle mass (58.0 vs. 55.2 cm 2 /m 2 , respectively; P < 0.001) and decreased body mass index (BMI) (27.9 vs. 26.3 kg/m 2 , respectively; P = 0.05), but fat mass was increased (68.9 vs. 72.0 cm 2 /m 2 , respectively; P = 0.01). Patients with low SMI at diagnosis showed no significant changes in body composition parameters and no improvement of SMI, even with nutritional support. Low SMI (hazard ratio [HR]: 1.8; 95% confidence interval [CI]: 1.02-3.16) was an independent predictor (P = 0.041) of high nutritional risk index (HR: 1.79; 95% CI: 1.03-3.11; P = 0.039) at diagnosis., Conclusions: The percentage of patients with a low SMI increased during follow-up. Our data suggest that an assessment of skeletal muscle parameters and nutrition support may be more useful in patients with a high SMI., (© 2021. The Author(s).)

Objective: To retrospectively evaluated the prognostic significance of post-radiotherapy parametrial involvement (PMI), the necessity of parametrial resection, and the optimal salvage surgery in locally recurrent or persistent cervical cancer developed after radiotherapy., Methods: Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery were identified, and the prognostic impact of post-radiotherapy PMI on patient's survival was first investigated. Then, the optimal salvage surgery for patients with post-radiotherapy PMI as well as the predictors for post-radiotherapy PMI were evaluated., Results: A total of 60 patients underwent salvage surgery for recurrent or persistent diseases. Of these, 21 (35.0%) showed post-radiotherapy PMI (PMI-group). Patients in PMI-group showed significantly shorter progression-free survival (PFS) than those in non-PMI-group (p = 0.01). In both PMI-group and non-PMI-group, PFS was affected by the completeness of salvage surgery. In non-PMI-group, less radical surgery achieved similar therapeutic efficacy to more radical surgery (3-year PFS rates: 62.5% versus 54.1%, p = 0.91). In contrast, in PMI-group, not less radical surgery but more radical surgery achieved curative therapeutic efficacy (3-year PFS rate: 0% versus 28.9%). Maximum tumor diameter, deep stromal invasion, and LVSI were found to be predictors of post-radiotherapy PMI., Conclusion: Post-radiotherapy PMI is an indicator of short survival after salvage surgery in patients with locally recurrent or persistent cervical cancer developed after radiotherapy. Both less radical and more radical surgery have curative therapeutic efficacies in patients without post-radiotherapy PMI, if the tumor could be resected with an adequate surgical margin. Thus, hysterectomy type should be tailored to the risk for post-radiotherapy PMI., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2021. Published by Elsevier Masson SAS.)

Importance: Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer., Objectives: To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes., Design, Setting, and Participants: This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020., Exposure: Nonmetastatic colon cancer., Main Outcomes and Measures: The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves., Results: A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years; 22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR, 5.92 [95% CI, 4.04-8.00]; P = .02). Patients with low SMA who developed a cancer recurrence, compared with those who did not, had higher C-reactive protein (mean [SD], 31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003), IL-6 (mean [SD], 1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004), VEGF (mean [SD], 310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = .007), and CD14 (mean [SD], 521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03) expression and lower albumin (mean [SD], 3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01), IL-2 (mean [SD], 0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P < .001), IL-10 (mean [SD], 8.15 [1.09] ng/mL vs 16.32 [4.43] ng/mL; P = .004), and interferon γ (mean [SD], 2.61 [1.36] ng/mL vs 14.87 [3.43] ng/mL; P = .02) levels. Patients with high visceral to total fat ratio who developed recurrence had higher levels of IL-6 (mean [SD], 5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P = .03) and tumor necrosis factor α (mean [SD], 5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P = .03)., Conclusions and Relevance: These findings suggest that low SMA and high visceral to total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.

Research Question: Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas?, Design: This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes., Results: The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups., Conclusions: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Long-term functional outcomes are poorly characterized for salvage laryngectomy. We identified predictors of esophageal stricture and swallowing function after salvage laryngectomy in a large cohort., Methods: A retrospective study of 233 patients who underwent salvage total laryngectomy for recurrent/persistent squamous cell carcinoma of the larynx or hypopharynx after radiation (XRT) or chemoradiation (CRT) was performed. Primary outcomes were esophageal dilation within 1 year, time to dilation, and gastrostomy tube dependence. Multivariate logistic and Cox regressions were used for statistical analysis., Results: Dilation was performed in 29.9% of patients. Dilation was twice as likely in patients with post-operative fistula compared to those without (Hazard Ratio (HR) 2.10, 95% Confidence Interval (CI) 1.06-4.13, P = .03). Every year between XRT/CRT and salvage was associated with 10% increase in dilation (HR 1.09, 95% CI 1.03-1.17, P = .01). No factors were associated with dilation by 1 year. About 10% of patients were at least partially gastrostomy tube-dependent 1 year post-operatively. At last follow-up (median 29 months), this rate was 13%. Patients with supraglottic recurrence had an increased risk of gastrostomy tube dependence at 1 year compared to glottic (OR 16.7, 95% CI 1.73-160, P = .02). For every 10 pack years pre-salvage, the OR of requiring tube feeds at last follow-up was 1.24 (95% CI 1.04-1.48, P = .02)., Conclusions: Fistula and pre-salvage smoking were associated with stricture post-salvage laryngectomy. No factors were associated with dilation by 1 year. Supraglottic recurrence and smoking were associated with gastrostomy tube dependence. These findings are important for pre-operative counseling prior to salvage laryngectomy., Level of Evidence: Level 4 Laryngoscope, 131:1229-1234, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Purpose: This study aimed to establish new criteria for limited resection of non-small cell lung cancer (NSCLC) based on computed tomography findings and maximum standardized uptake value (SUVmax)., Methods: Between December 2007 and December 2015, 611 patients underwent lung cancer surgery; of these, 70 with cT1aN0M0 who underwent limited resection were enrolled. Criteria for undergoing intentional limited resection (ILR) were (1) tumor ground-glass opacity (GGO) ratio of ≥ 0.75 and (2) tumor SUVmax ≤ 1.5. Patients who met criteria (1) and (2) underwent partial resection, and those who only met criteria (2) underwent segmentectomy as ILR. The control group was subjected to limited surgery without meeting the criteria., Results: Overall, 45 and 25 patients who met the criteria were included in the ILR and control groups, respectively. In the ILR group, 13 patients underwent partial resection, and 32 underwent segmentectomy; in the control group, 18 patients underwent partial resection and 7 underwent segmentectomy. According to our criteria, no relapsed cases occurred in the ILR group, although six patients showed recurrence of lung cancer in the control group. The 5-year overall survival (OS) rates in the ILR and control groups were 100% and 67.7%, respectively, and the relapse-free survival (RFS) rates were 100% and 61.6%, respectively. The log-rank test showed that this difference was statistically significant (OS: P < 0.0001, RFS: P < 0.0001)., Conclusions: SUVmax may serve as a predictive marker of recurrence to determine the treatment strategy for patients with NSCLC. Patients with low GGO ratio and low SUVmax may be cured by limited resection.

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC., Competing Interests: The authors have declared that no competing interests exist.

Background: Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis., Results: To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as 'low risk' by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0-3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score., Conclusions: This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0-3).

To explore the predictive performance of machine learning on the recurrence of patients with gastric cancer after the operation. The available data is divided into two parts. In particular, the first part is used as a training set (such as 80% of the original data), and the second part is used as a test set (the remaining 20% of the data). And we use fivefold cross-validation. The weight of recurrence factors shows the top four factors are BMI, Operation time, WGT and age in order. In training group:among the 5 machine learning models, the accuracy of gbm was 0.891, followed by gbm algorithm was 0.876; The AUC values of the five machine learning algorithms are from high to low as forest (0.962), gbm (0.922), GradientBoosting (0.898), DecisionTree (0.790) and Logistic (0.748). And the precision of the forest is the highest 0.957, followed by the GradientBoosting algorithm (0.878). At the same time, in the test group is as follows: the highest accuracy of Logistic was 0.801, followed by forest algorithm and gbm; the AUC values of the five algorithms are forest (0.795), GradientBoosting (0.774), DecisionTree (0.773), Logistic (0.771) and gbm (0.771), from high to low. Among the five machine learning algorithms, the highest precision rate of Logistic is 1.000, followed by the gbm (0.487). Machine learning can predict the recurrence of gastric cancer patients after an operation. Besides, the first four factors affecting postoperative recurrence of gastric cancer were BMI, Operation time, WGT and age.

Background: Sorensen Test time-to-task-failure (TTF) predicts several low back pain (LBP) clinical outcomes, including recurrence. Because the test is described as a measure of trunk extensor (TE) muscle endurance, LBP rehabilitation programs often emphasize endurance training, but the direct role of TE muscle function on Sorensen Test-TTF remains unclear., Objective: To assess the discriminative and associative properties of multiple markers of isolated TE performance with regard to Sorensen Test-TTF in individuals with recurrent LBP., Method: Secondary analysis of baseline measures from participants in a registered (NCT02308189) trial (10 men; 20 women) was performed. Participants were classified by Sorensen Test-TTF as high, moderate or low risk for subsequent LBP episodes, and compared to determine if classification could discriminate differences in TE function. Correlations between Sorensen Test-TTF and isolated TE performance, anthropometrics and disability were investigated., Results: Individuals at risk of subsequent LBP episodes had greater perceived disability and fat mass/TE strength ratios (P⩽ 0.05) than those not at risk. Modest, significant (r= 0.36-0.42, P⩽ 0.05) associations were found between Sorensen Test-TTF, TE endurance and fat mass/TE strength. Exploratory analyses suggested possible sex-specific differences related to Sorensen Test-TTF., Conclusions: Isolated TE muscle endurance is only one of several factors with similar influence on Sorensen Test-TFF, thus LBP rehabilitation strategies should consider other factors, including TE strength, anthropometrics and perceived disability.

Purpose: This study aimed to identify unobserved distinct latent classes/subgroups of breast cancer (BC) patients in China with respect to various sexual health measures and examine the association of the latent membership with individual characteristics., Methods: In a cross-sectional study, 123 BC patients were analyzed. Their sexual health was measured using the Female Sexual Functioning Index (FSFI). Latent class analysis (LCA) was used to examine the patterns of sexual health in patients. Associations of the latent class membership with individual characteristics were examined using multinomial logistic regression., Results: Three a priori unknown distinct latent classes of patients were identified with respect to the 19 FSFI sexual health measures: 50 patients (41.6%) were classified in class 1 "No Impairment Group," 49 patients (39.4%) in class 2 "Organic Sexual Dysfunction Group," and 24 patients (19.1%) in class 3 "Poor Sexual Health Group." Income and anxiety were positively, whereas disease duration was negatively associated with the likelihood of being in class 2 than in class 1, patients with recurrence of cancer were likely to be in classes 2 and 3. Patients classified in class 3 were more likely to have better prior body image and have more severe menopausal symptoms, whereas less likely to have better post body image and have better partner relationships., Conclusion: The findings revealed the heterogeneity of sexual health among BC patients in China and may guide to identify the high-risk patients and enable early intervention.

A 70-year-old woman was referred to our department due to a solitary mediastinal tumor which gradually grew near the site of anastomosis for 8 years after radical surgery of esophageal squamous cell carcinoma. It was difficult to distinguish the lymph node recurrence of esophageal cancer from another tumor of unknown primary origin. Endoscopic ultrasound-guided fine-needle aspiration was performed, and the tumor was diagnosed to be neuroendocrine carcinoma. She received concurrent chemoradiotherapy with etoposide plus cisplatin. After the completion of chemoradiotherapy, the tumor disappeared. A solitary growing tumor which develops after radical resection of cancer would be better to be examined histologically in order to make an accurate diagnosis and select the most appropriate treatment.

Background/Aim: There is an increasing demand for preserving the fertility of young women impacted with early-stage cervical cancer. The aim of this study is to evaluate the oncological and reproductive outcomes of abdominal radical trachelectomy ( ART ). Patients and Methods: We retrospectively reviewed patients with FIGO stageIA2-IB1 cervical cancer who underwent ART from 2007 to 2018. We also compared the oncological prognosis between the patients who underwent ART and radical hysterectomy ( RH ). Results: A total of 42 patients underwent ART. During median follow-up 62.5 months, there were 4 ( 9.5% ) recurrences and 1 ( 2.4% ) death. As for tumors ≤2 cm, the 5-year recurrence-free survival (RFS) rate and overall survival (OS) rate for patients who underwent ART was similar to those who underwent RH (89.8% vs. 92.7%, p =0.42 and 97.3% vs. 95.0%, p =0.44, respectively ). Nineteen patients attempted to conceive and seven of them were successful. There was one case of a first-trimester miscarriage, two cases of preterm delivery, three cases of full-term delivery and one ongoing pregnancy. Conclusion: ART could be a feasible alternative to RH for patients with tumors ≤2 cm with comparable oncological outcome., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We herein report three cases of patients with an ampullary neuroendocrine tumor (NET), who underwent endoscopic papillectomy (EP). No tumor recurrence or metastasis was detected in the patients for more than two years after EP. Generally, surgical resection is recommended for ampullary NETs by the European Neuroendocrine Tumor Society. However, as EP is less invasive than surgical resection, there are some reports of low-grade small ampullary NETs curatively treated by EP with long-term follow-up. We consider that EP may be a curative treatment for small and low-grade ampullary NETs without regional or distant metastasis.

Background/aim: Myxofibrosarcoma (MFS) is characterized by an infiltrative growth pattern. This study aimed to determine the correlation between overall survival (OS) and morphological features of MFS as well as examine the reproducibility of these findings on preoperative magnetic resonance imaging (MRI)., Patients and Methods: Fifty-eight MFS patients underwent preoperative MR imaging with the following features analysed: i) tumour size, ii) localization, iii) margins, iv) morphology, v) signal characteristics, vi) contrast enhancement, vii) presence and extent of perilesional oedema, and viii) presence of the tail sign., Results: Only circumscribed perilesional oedema was associated with a significantly better survival compared to diffuse oedema (p=0.010), which was found in the majority of cases. The tail sign was found in less than 50% of the cases. Cohen's kappa coefficients confirmed a relatively high interrater variability., Conclusion: Perilesional diffuse oedema on MR imaging of MFS is significantly correlated with a poor overall survival. The interrater variability in interpretation of MR examinations varies from slight to substantial agreement. Preoperative MR imaging with detailed planning of the resection seem to be a logical approach to achieve negative resection margins and recurrence-free survival., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Importance: Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear., Objective: To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation., Design, Setting, and Participants: This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020., Exposures: Untreated metastatic breast cancer., Main Outcome and Measures: The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings., Results: Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival., Conclusions and Relevance: These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

Background: Limited evidence exists regarding the cost and health-related quality of life (HRQoL) effects of non-muscle-invasive bladder cancer (NMIBC) recurrence and progression to muscle-invasive bladder cancer (MIBC). We examined these effects using evidence from a recent randomized control trial., Material and Methods: The costs and HRQoL associated with bladder cancer were assessed using data from the BOXIT trial (bladder COX-2 inhibition trial; n = 472). The cost and HRQoL effects from clinical events were estimated using generalized estimating equations. The costs were derived from the recorded resource usage and UK unit costs. HRQoL was assessed using the EQ-5D-3L and reported UK preference tariffs. The events were categorized using the TMN classification., Results: Cases of grade 3 recurrence and progression were associated with statistically significant HRQoL decrements (-0.08; 95% confidence interval [CI], -0.13 to -0.03; and -0.10; 95% CI, -0.17 to -0.03, respectively). The 3-year average cost per NMIBC patient was estimated at £8735 (95% CI, 8325-9145). Cases of grade 1, 2, and 3 recurrence were associated with annual cost effects of £1218 (95% CI, 403-2033), £1677 (95% CI, 920-2433), and £3957 (95% CI, 2332-5583), respectively. Progression to MIBC was associated with an average increase in costs of £5407 (95% CI, 2663-8152)., Conclusion: Evidence from the BOXIT trial suggests that patients with NMIBC will both experience decrements in HRQoL and incur significant costs, especially in the event of a grade 3 recurrence or a progression to MIBC., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recurrence of breast cancer is a predominant fear for patients who were treated for breast cancer. Acute and late dermatologic effects of radiotherapy are not uncommon and could have similar characteristics to breast cancer recurrence. Thus, it is important to highlight key differences between the clinical and histologic presentations of radiation effects and recurrence. Herein, we present two patients who presented with late dermatologic effects of radiotherapy months to years after treatment, neither of whom had workup consistent with cancer recurrence. We provide clinical and microscopic descriptions of each case and provide a review to differentiate various dermatologic conditions. This report aims to outline potential late dermatologic effects of radiation treatment and emphasise that changes in the breast do not always signal breast cancer recurrence., (© 2020 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Purpose: To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI)., Methods: Melanoma survivors were identified within two study populations ( N = 104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up., Results: Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence ( N = 8), existential problems ( N = 2), survivor guilt ( N = 2), and posttraumatic stress disorder ( N = 6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity ( N = 8), hepatitis ( N = 1), colitis ( N = 3), and sarcoidosis ( N = 1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF., Conclusion: A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920., Competing Interests: AR reports personal fees from Bristol-Myers Squibb and Merck Sharp & Dohme, outside the submitted work. GA and JKS report travel accommodations—Merck Sharp & Dohme, Pfizer, and Astellas—outside the submitted work. AS and PM report to be full-time employees of Cogstate Ltd, the company that provided the computerized cognitive tests in this study. BN reports grants and personal fees from Novartis, personal fees from Bristol-Myers Squibb, personal fees from Merck Sharp & Dohme, grants and personal fees from Pfizer, personal fees from AstraZeneca, and grants and personal fees from Roche, outside the submitted work. CL, JL, MD, JC, and PT report no conflict of interest., (Copyright © 2020 Anne Rogiers et al.)

Background : Stereotactic body radiation therapy (SBRT) results in high local control (LC) rates in patients with non-small cell lung cancer (NSCLC). For central lung tumors, risk-adapted fractionation schedules are used and underdosage to the Planned Target Volume (PTV) is often accepted to respect the dose constraints of the organs at risk in order to avoid high rates of toxicity. The purpose of this study was to analyze the effect of PTV underdosage and other possible prognostic factors on local- and disease control after SBRT in patients with central lung tumors. Material and Methods : Patients with centrally located NSCLC treated with SBRT were included. The doses were converted into biologically equivalent dose using α/β-value of 10 Gy (BED 10 ). Underdosage to the PTV was defined as the (percentage of) PTV receiving less than 100 Gy BED 10 ; (%)PTV < 100 BED 10 . Potential prognostic factors for LC and Disease Free Survival (DFS) were evaluated using Cox regression analysis. Results : Two hundred and twenty patients received ≤12 fractions of SBRT. LC-rates were 88% at 2 years and 81% at 3 years. Twenty-seven patients developed a local recurrence. Both the PTV < 100 BED 10 and %PTV < 100 BED 10 were not prognostic for LC. Tumor size and forced expiratory volume in 1 second (FEV 1 ) were independently prognostic for LC. Disease progression was reported in 75 patients with DFS-rates of 66% at 2 years and 56% at 3 years. Disease recurrence was independent significantly associated with larger tumor diameter, lower lobe tumor location and decreased FEV 1 . Grade 4-5 toxicity was reported in 10 patients (8 with ultra-central tumors) and was fatal in at least 3 patients. Conclusion : Decrease in tumor coverage was not correlated with the local recurrence probability. The LC and DFS were promising after SBRT of centrally located NSCLC with tumor size, FEV 1 and tumor location (for DFS only) as prognostic factors.

A 74-year-old man presented with recurrent syncope 3 months after definitive surgery for hypopharyngeal cancer. The patient experienced dizziness and severe hypotension on the movement of the neck and head. CT revealed disease recurrence with masses encasing the left internal carotid artery. The patient was diagnosed with vasodepressor type of tumour-induced carotid sinus syndrome (tiCSS) and was referred for palliative intensity-modulated radiotherapy (IMRT). Ten days after the commencement of IMRT (25 Gy in five fractions), the symptoms of tiCSS improved, and there was no re-exacerbation of the symptoms till the patient died 56 days after the commencement of RT. Palliative IMRT was feasible and effective for recurrent malignant tiCSS. Given the fact that palliative IMRT is minimally invasive, this option could be widely adapted for patients with such poor general condition and prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper has two main purposes: (1) to report a rare case of paediatric gliosarcoma that invaded the surrounding orbit and (2) to demonstrate chlorpromazine injection as a potential treatment option for blind, painful eye caused by tumour invasion. A 12-year-old man who presented with headaches was found to have glioblastoma multiforme and it was excised and treated with radiation and chemotherapy. Seven months later, the tumour recurred as gliosarcoma, a rare variant of glioblastoma multiforme containing distinct gliomatous and sarcomatous components. In spite of treatment, the tumour progressed and eventually invaded into the right orbit. He subsequently developed a proptotic, blind, painful eye and was treated with retrobulbar chlorpromazine injection, which provided immediate symptomatic relief., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.

Cancer is an important cause of morbidity and mortality after liver transplantation and can occur through three mechanisms: recurrence of a recipient's pre-transplant malignancy, donor-related transmission and de novo development. Currently, the decision to list a patient with a history of malignancy is an individual one. Screening guidelines for potential donors and for recipients after transplant are still widely based on general population guidelines, while the role of chronic immunosuppression remains controversial. These shortcomings mean that patients present at diagnosis with advanced stages of the disease, often precluding curative treatments. The present review summarizes current recommendations for the screening of recipients and donors for pre- and post-transplant malignancies, and current management of recipients who develop cancer after a liver transplant., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD)., Methods: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model., Results: Compared with white women ( n = 191), black women ( n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m 2 vs. 30.6 ± 7.0 kg/m 2 , P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = -0.323 cm 3 ; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm 3 ; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = -0.063%, SE = 0.011; postmenopausal slope = -0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD ( P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098)., Conclusions: Race does not appear to impact ET-related longitudinal changes in VBD., Impact: Racial disparities in estrogen receptor-positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET., (©2020 American Association for Cancer Research.)

Objectives: To evaluate long-term olfactory outcomes in patients who underwent pituitary surgery through the endoscopic endonasal transsphenoidal approach (EETSA) by T&T olfactometer., Methods: We retrospectively reviewed 26 patients who underwent pituitary surgery via EETSA. Olfactory function was assessed by T&T olfactometer before and 6 months after surgery. The mean of recognition thresholds for five different odorants was used. The change in the mean recognition threshold values was evaluated in the entire cohort and the subgroup analysis was performed according to the age, sex, past history of pituitary surgery (primary surgery or revision surgery), histopathology (non-functioning adenoma (NFA) or functioning adenoma (FA)), reconstruction procedure (rescue flap or nasoseptal flap), and superior turbinate management (preserved or resected)., Results: Of the 26 patients (12 men and 14 women, median age 53 years), 21 patients were newly diagnosed with pituitary gland tumor (16 NFAs, 5 FAs) and the remaining 5 were diagnosed with recurrent pituitary gland tumor (4 NFAs and 1 FA). In the whole cohort, the mean recognition threshold values of T&T olfactometer significantly improved after surgery (P=0.01). Thirteen out of 26 patients (50%) showed olfactory improvement, whereas only 3 (12%) showed deterioration. In the subgroup analysis, olfactory function outcomes were not significantly different between the subgroups with respect to the age, sex, past history of pituitary surgery, histopathology, reconstruction procedure, or superior turbinate management. The olfactory function tended to worsen in the revision surgery group compared to that in the primary surgery group, but not significantly (P=0.06)., Conclusions: The olfactory function was improved or maintained after pituitary surgery via EETSA in 88% of patients, indicating the benefits of low invasiveness of our surgical treatment. On the other hand, three patients (12%) demonstrated deterioration of olfactory function, suggesting that the risk of postoperative olfactory dysfunction should be informed to patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: En bloc excision has been increasingly used for the management of giant cell tumors (GCTs) in the distal radius. An osteoarticular allograft has been used extensively for decades, and custom-made prosthesis reconstruction has been more recently applied. We aimed to compare the clinical outcomes of the two procedures., Methods: We retrospectively analyzed 30 patients with Campanacci III or recurrent GCTs of the distal radius for follow-up at a mean of 33.2 months. In total, 15 underwent osteoarticular allograft reconstruction (allograft group) and 15 received cementless three-dimensional (3D)-printed prosthesis reconstruction (prosthesis group) between March 18, 2013, and May 20, 2018. All patients underwent by clinical and radiological examinations, including pre- and postoperative active range of motion (ROM) of the wrist, VAS score, grip strength, degenerative change of wrist, Mayo wrist score and Musculoskeletal Tumor Society (MSTS) score. Complications were evaluated using the Henderson classification., Results: Both groups showed significantly increased ROM, grip strength, Mayo score and MSTS score postoperatively. Furthermore, the extension, flexion, MSTS, and Mayo score were significantly higher in the prosthesis group. There was no significant difference in grip strength and VAS between the groups. In allograft group, one patient had a late infection one had resorption of allograft without allograft bone fracture. and four had wrist subluxation. All patients had degenerative changes (mean 9 months). In the prosthesis group, three patients developed wrist subluxation, three had separation of the distal radioulnar joint, and none of the patients developed wrist degeneration., Conclusions: Our study compared the objective functional outcomes and complications of two reconstructive methods for Campanacci III or recurrent GCT in the distal radius. 3D-printed prosthesis replacement can partially preserve wrist function better than allograft reconstruction in the short-term. During the design of 3D-printed prosthesis, preoperative morphological assessment of the affected proximal row carpal is helpful to control postoperative dislocation. After allograft reconstruction, wrist degeneration, which has been demonstrated in all patients, severely influence their wrist function. Therefore, compared to allograft reconstruction, 3D-printed prosthesis reconstruction has irreplaceable advantages at early-stage application, especially in wrist function, however, further studied with a larger number of cases and longer follow-up.

Objective: To describe the natural history of untreated muscle-invasive bladder cancer (MIBC) and compare the oncological outcomes of treated and untreated patients., Patients and Methods: We utilised a database encompassing all patients with newly diagnosed bladder cancer in Stockholm, Sweden between 1995 and 1996. The median follow-up for survivors was 14.4 years. Overall, 538 patients were diagnosed with bladder cancer of whom 126 had clinically localised MIBC. Patients were divided into two groups: those who received radical cystectomy or radiation therapy, and those who did not receive any form of treatment. Multivariable Cox or competing-risks regressions were adopted to predict metastasis, overall survival (OS), and cancer-specific mortality (CSM), when appropriate. Analyses were adjusted for age at diagnosis, sex, tumour stage, clinical N stage, and treatment., Results: In all, 64 (51%) patients did not receive any definitive local treatment. In the untreated group, the median (interquartile range) age at diagnosis was 79 (63-83) vs 69 (63-74) years in the treated group (P < 0.001). Overall, 109 patients died during follow-up. At 6 months after diagnosis, 38% of the untreated patients had developed metastatic disease and 41% had CSM. The 5-year OS rate for untreated and treated patients was 5% (95% confidence interval [CI] 1, 12%) vs 48% (95% CI 36, 60%), respectively. Patients not receiving any treatment had a 5-year cumulative incidence of CSM of 86% (95% CI 75, 94%) vs 48% (95% CI 36, 60%) for treated patients. Untreated patients had a higher risk of progression to metastatic disease (hazard ratio [HR] 2.40, 95% CI 1.28, 4.51; P = 0.006), death from any cause (HR 2.63, 95% CI 1.65, 4.19; P < 0.001) and CSM (subdistribution HR 2.02, 95% CI 1.24, 3.30; P = 0.004)., Conclusions: Untreated patients with MIBC are at very high risk of near-term CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.

Objective: The role of repeat resection for recurrent glioblastoma multiforme (rGBM) is unclear. This large comparative cohort study assessed overall survival (OS), survival since recurrence (SSR), quality of life, and complications in reoperated versus non-reoperated patients for rGBM., Patients and Methods: All patients with rGBM between 2005 and 2015, who were discussed by our institution's multi-disciplinary team, and who either did or did not undergo reoperation, were prospectively followed up with data collected and compared. Survival and prognostic factors were analysed using Kaplan-Meier and Cox regression methods., Results: 312 patients (reoperated, n = 145; non-reoperated, n = 167) were analysed. Median SSR was 10.8 months and 6.9 months in the reoperated and non-reoperated groups respectively (Log-rank test: p = 0.02). Median OS was 24.1 months and 20.4 months in the reoperated and non-reoperated groups, respectively (Log-rank test: p = 0.04). Quality of life as measured by Short Form 36 scores were 59 versus 54 at baseline and 62 versus 51 at four-month follow-up for re-operated and non-reoperated groups, respectively (p < 0.05). Age < 60 years, Karnofsky Performance Status (KPS) ≥ 80, recurrence ≥ 9 months from initial diagnosis, methylguanine methyltransferase (MGMT) promoter methylation, and extent of resection (EOR) > 80 %, each were significant predictors of SSR and OS. Complication rates were 5.5 % and 6.2 % following repeat resection and primary resection, respectively (p > 0.05)., Conclusion: This is the first large prospective comparative cohort study of rGBM and demonstrates that repeat resection confers a small but significant benefit in survival and quality of life over non-operative treatment. Best prognosis is associated with: younger age, KPS ≥ 80, late recurrence, MGMT promoter methylation and EOR > 80 %., (Copyright © 2019. Published by Elsevier B.V.)

Background: Navigated transcranial magnetic stimulation (nTMS) is being used for different purposes in patients with brain tumors. However, the procedure requires a positive electrophysiological response. For patients with negative response in rest conditions, active motor threshold (AMT) may be used. However, sometimes it is difficult to obtain AMT measures owing to inability of the patient to sustain steady muscle contraction. Herein, we describe a simple method by using a hand dynamometer to obtain AMT measures during nTMS session., Case Description: A woman aged 68 years underwent total removal of a right frontal lobe oligodendroglioma World Health Organization grade II 15 years ago. Cranial magnetic resonance imaging during follow-up revealed local recurrence. In the postoperative period, she developed left upper limb paresis. A postoperative nTMS session was performed for motor electrophysiological evaluation. However, using the standard technique for AMT measurement, the patient was unable to perform sustained muscle contraction as required. A hand dynamometer was used. It allowed sustained muscle contraction for AMT measurement. A counter force for the index finger flexion, the hand support to stabilize hand joints, and a numerical screen serving for both the examiner and the patient as a feedback parameter may explain the success obtained with this simple device., Conclusions: Although more studies are necessary to validate the method, the hand dynamometer should be considered for patients unable to sustain muscle contraction during AMT measurement., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Composite tumor of larynx, a recently included entity in the current WHO classification, is often a difficult pathological diagnosis, especially in small biopsies. We report a case of laryngeal composite tumor, initially misdiagnosed as squamous cell carcinoma, which later turned out to be composite in nature, with associated neuroendocrine (small cell carcinoma) component. This report emphasizes the need for obtaining deeper biopsies and their thorough pathological examination to improve the diagnostic accuracy. Keywords: combined small cell carcinoma; composite tumor; larynx; small cell carcinoma; squamous cell carcinoma.

Lipomatous ganglioneuromas are a rare variant of ganglioneuromas characterized by a mature adipocytic component admixed with a conventional ganglioneuroma component. We present the case of a 34 year old patient with a paravertebral right lesion L1-L4 with intraspinal extension and secondary neurological deficit, who underwent surgery in our hospital. The pathological anatomy showed a yellowish encapsulated neoplasm, which under microscopic evaluation showed areas of ganglioneuroma admixed with areas of mature fat. In the follow up, the patient was asymptomatic, had recovered paresis in the right lower extremity and in the last image control did not present data of lesion recurrence. Fewer than 10 cases of lipomatous ganglioneuromas have been reported in the literature, being this the first paravertebral case wih intraspinal extension and with neurological deficit, hence the interest of this work., (Copyright © 2019 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One of the most important factors affecting the risk of tumor recurrence and overall prognosis is perineural invasion and bone invasion. Perineural invasion is defined as a tumor spreading and the ability of tumor cells to penetrate around or through the nerve tissue. Perineural invasion can cause the tumor to spread to distant areas from the primary tumor location. One possible explanation for this is the formation of microenvironment in the perineural space which may contain cellular factors that act on both nerve tissue and some types of tumor tissues. Bone invasion by OSCC has major implications for tumor staging, choice of treatment, outcome and quality of life. Oral SCCs invade the mandibular or maxillary bone through an erosive, infiltrative or mixed pattern that correlates with clinical behavior. Bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. Some cytokines (e.g. TNFα and PTHrP) lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression in oral SCC cells and in cancer stromal cells to induce osteoclastogenesis. Oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. A more molecular-based clinical staging and tailor-made therapy would benefit patients with bone invasion by OSCC.

Introduction: With the development of economy and the acceleration of population aging, Prostate cancer (PCa) has presented a situation of high morbidity and mortality worldwide. The recent studies have shown that Chinese patent medicine combined with endocrine therapy in the treatment of prostate cancer not only plays a synergistic role in enhancing the efficacy. This review hopes to adopt meta-analysis to evaluate the efficacy and safety of Chinese patent medicine in the treatment of pain caused by prostate cancer and provides evidence for its application in clinical practice., Methods and Analysis: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to June 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of pain caused by prostate cancer., Ethics and Dissemination: This systematic review will evaluate the efficacy and safety of Chinese patent medicine for pain caused by prostate cancer. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial., Trial Registration Number: PROSPERO CRD42019131544.

Competing Interests: None

Background: Carcinoma ex pleomorphic adenoma (CA-ex-PA) is extremely unusual in minor salivary glands of oral cavity. CAex-PA is a carcinomatous change as a primary or as a recurrence of pleomorphic adenoma., Objective: Due to resemblance of clinical symptoms of Ca ex PA and benign pleomorphic adenoma, it is mandatory for surgeons to keep high degree of clinical alertness, considering the peculiarity of this tumor., Case Report: 54-year-old male presented with swelling on left side in the pre-auricular region from the middle of zygomatic arch to mastoid process and from tragus of the ear up to angle of mandible. Fine needle aspiration cytology revealed a mixture of benign and malignant components. Total left parotidectomy with left radical neck dissection followed by reconstruction with cervicodeltopectoral flap was performed. Combination of chemotherapy and radiotherapy were given to patient. Histologic examination and pre-operative fine needle aspiration cytology confirmed the diagnosis of Carcinoma ex pleomorphic adenoma (CA-ex-PA). Two-year follow-up of patient showed no recurrence of the lesion., Conclusion: Due to the similarity in the clinical symptoms of CA-ex-PA and benign pleomorphic adenoma, it is vital that clinicians maintain a high degree of clinical vigilance, considering the oddity of this malignancy., (© 2019 Khanna et al.)

Autophagy, a self-digestion intracellular catabolic process, plays a crucial role in cellular homeostasis under conditions of starvation, oxidative stress and genotoxic stress. The capability of maintaining homeostasis contributes to preventing malignant behavior in normal cells. Many studies have provided compelling evidence that autophagy is involved in brain tumor recurrence and chemotherapy and radiotherapy resistance. Gliomas, as the primary central nervous system (CNS) tumors, are characterized by rapid, aggressive growth and recurrence and have a poor prognosis and bleak outlook even with modern multimodality strategies involving maximal surgical resection, radiotherapy and alkylating agent-based chemotherapy. Autophagy-associated signaling pathways, such as the extracellular signal-regulated kinase1/2 (ERK1/2) pathway, class I phosphatidylinositol 3-phosphate kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and nuclear factor kappa-B (NF-κB) pathway, act as tumor suppressors or protect tumor cells against chemotherapy/radiotherapy-induced cytotoxicity in gliomagenesis. Through these pathways, both lethal autophagy and protective autophagy play crucial roles in tumor initiation, chemoresistance and glioma stem cell differentiation. Moreover, lethal autophagy and protective autophagy have been identified as novel therapeutic targets in glioma according to the mechanisms described above. Here, we discuss the multiple impacts of the autophagic response on distinct phases of gliomagenesis and the advanced progress of therapies based on this concept., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

During a two-year period (2001-2003), 464 patients were treated for tuberculosis at Jordanovac Department for Lung Diseases in Croatia. Besides pulmonary tuberculosis in 97.7% of patients, patients were also treated for tuberculous pleurisy (0.9%), tuberculous laryngitis (0.6%), tuberculous meningitis (0.2%), tuberculous pericarditis (0.2%) and urogenital tuberculosis (0.4%). Out of the total number of patients, 57.3% declared themselves to be active smokers (men were predominant and made up to 80.8%) and 20.9% to be active alcohol consumers. Both risk factors, i.e. smoking and alcohol consumption, were present in 15.1% of all patients. The most common comorbidities were diabetes mellitus (30.4%), cardiac diseases (11.2%) and chronic obstructive pulmonary disease (8.0%). Lung carcinoma was the most common malignant disease (n=51), with Mycobacterium tuberculosis isolated in 33% of them. Seventy-two of 464 (15.5%) patients had recurrences of tuberculosis. Of these, 30.5% had one of the risk factors (20.8% were smokers and 9.7% consumed alcohol), while 32.5% of patients had both risk factors. In conclusion, cigarette smoking was proved to be the most significant risk factor for development of pulmonary tuberculosis and its recurrence.

As cancer advances, cells often spread from the primary tumor to other parts of the body and form metastases. This is the main cause of cancer related mortality. Here we investigate a conceptually simple model of metastasis formation where metastatic lesions are initiated at a rate which depends on the size of the primary tumor. The evolution of each metastasis is described as an independent branching process. We assume that the primary tumor is resected at a given size and study the earliest time at which any metastasis reaches a minimal detectable size. The parameters of our model are estimated independently for breast, colorectal, headneck, lung and prostate cancers. We use these estimates to compare predictions from our model with values reported in clinical literature. For some cancer types, we find a remarkably wide range of resection sizes such that metastases are very likely to be present, but none of them are detectable. Our model predicts that only very early resections can prevent recurrence, and that small delays in the time of surgery can significantly increase the recurrence probability., Competing Interests: The authors have declared that no competing interests exist.

Background: Tuberculum sellae meningiomas frequently extend into the optic canals, which leads to a progressive longitudinal visual loss. Therefore, in addition to tumor removal, unroofing and exploration inside the optic canal are important procedures., Objective: To perform endoscopic endonasal tumor removal with optic canal decompression for small primary or recurrent meningiomas associated with a progressive visual loss at the inferior-medial optic canal, which corresponded to a blind corner in the ipsilateral pterional/subfrontal approach., Methods: We retrospectively reviewed 2 cases of primary meningiomas that arose in the inferior-medial optic canal and 4 recurrent cases from the remnant inside the medial optic canal that had previously undergone craniotomy for tuberculum sellae meningiomas, and were treated by the endoscopic endonasal approach., Results: All tumors were detectable and could be removed without manipulation of the affected optic nerve. The average maximum diameter of the tumor was 8.4 mm (range: 5-12 mm). Two patients who had a long history of progressive visual disturbance and papillary atrophy did not recover from severe visual disturbances postoperatively. However, others showed considerable improvement, maintaining postoperative visual function during follow-up. There were no postoperative complications., Conclusion: Endoscopic endonasal approach has several advantages for meningiomas in the medial optic canal and associated with progressive visual disturbance. In surgery of tuberculum sellae meningiomas, optic canal decompression and exploration inside the optic canal are important procedures to avoid symptomatic recurrence, which may be facilitated by the endoscopic endonasal approach. Papillary atrophy and duration of visual deterioration are predictive factors for postoperative visual outcomes., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: The aim of this study was to assess the effect of cancer-related genes and their mutations analyzed by next-generation sequencing (NGS) on the oncological outcome after resection of colorectal liver metastases (CRLM)., Background: Traditional prognostic scores include clinical and pathological parameters of primary tumor and metastases. The modified clinical risk score (m-CS), based on size of metastases, primary tumor nodal status, and RAS mutation status outperformed traditional scores. We hypothesized to further improve the scoring system based on the results of NGS., Methods: Cancer tissues of 139 patients with CRLM were used for NGS. The work-up included the analysis of recurrent somatic mutations and copy number changes of 720 genes. Clinical data were extracted from a prospectively collected institutional liver database., Results: Depending on significance, the following cancer-related genes and their alterations (%) were further investigated: APC (86%), TP53 (78%), KRAS (29%), SMAD4 (15%), PIK3CA (14%), BRAF (8%), ERBB2 (6%), SMAD3 (5%), SMAD2 (4%), and NRAS (4%). The most predictive parameters for poor oncological outcome were alterations in the SMAD family (P = 0.0186) and RAS-RAF pathway (P = 0.032). Refining the m-CS by replacing RAS with RAS-RAF pathway and adding SMAD family resulted in an extended clinical risk score which is highly predictive for oncological outcome (P < 0.0001)., Conclusion: In conclusion, mutations of the SMAD family revealed a strong prognostic effect after surgery for CRLM. Integration of alterations of the SMAD family as well as the RAS/RAF pathway resulted in a new, still simple but highly prognostic score.

Background: Preservation of contralateral mucosa with microscopic tumor invasion in unilateral septal involvement increases the recurrence risk. The purpose of this study was to analyze the risk of invasion of contralateral mucosa in unilateral septal involvement of cancer and to risk stratify patients., Methods: Retrospective chart review of patients with histologically proven malignancy with unilateral septal involvement and absence of gross septal tumor involvement on the contralateral side were included., Results: Among 40 patients, majority (55%) belonged to sixth and seventh decade. The most common type was squamous cell carcinoma (63%). Approximately one-fourth (23%) showed microscopic contralateral invasion. Females (OR 12; 95% CI 2.01-71.35) and patients with septal bone invasion (OR 28.5; CI 3.35-242.0) had a higher risk of developing contralateral mucosal invasion., Conclusion: Complete resection of contralateral mucosa is preferred in areas along the bony septum. When complete resection is not performed, intraoperative frozen section is strongly recommended., (© 2019 Wiley Periodicals, Inc.)

Due to the higher incidence of hormone responsive tumours in women >50, the safety of hormone replacement therapy (HRT) in older breast cancer survivors may differ from younger age groups. The primary outcome in this review was the risk of tumour recurrence and secondary outcome the relationship with breast cancer-related mortality. Medline, CINAHL, Cochrane, Google Scholar and EMBASE databases were searched through August 2018 for studies reporting exposure to HRT in survivors ≥50 at primary diagnosis. Random effects models were used to estimate the combined relative risk (RR) of tumour recurrence and breast cancer-related mortality using the Mantel-Haenszel method and the quality of evidence determined for the primary outcome. Overall, nine studies (four cohort, one case-control, four RCTs; n = 16,002) were included. Very low quality evidence from observational studies demonstrated no adverse effect on tumour recurrence with HRT use (RR 0.80, 95% CI 0.53 to 1.19; I 2  = 66%; n = 11,984), while moderate quality evidence from RCTS demonstrated an adverse effect (RR 1.46, 95% CI 1.20 to 1.77; I 2  = 17%; n = 4108). Similarly, observational studies demonstrated no adverse effect on breast cancer-related mortality (RR 0.32, 95% CI 0.21 to 1.49; I 2  = 0%, n = 2182), while RCTs demonstrated a non-significant higher risk (RR 1.07, 95% CI 0.77 to 1.49; I 2  = 0%; n = 3918). Ultimately, despite conflicting findings, evidence of sufficient quality suggests that HRT may increase the risk of tumour recurrence in older survivors. However, adverse effect on mortality is unlikely. Caution with HRT use in survivors is further advised., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Even though both the involvement of regional lymph nodes and the number of metastatic lymph nodes are regarded as major determinants of survival in cutaneous melanoma, the extent of node dissection has been analyzed as an independent prognostic indicator in only a few studies. This study aims to determine how the extent of lymph node excision (EN) might predict the disease relapse and survival in melanoma., Methods: A total of 317 patients with stage III melanoma were included in the study and reviewed retrospectively. The patients were divided into 2 groups based on the number of the excised lymph nodes: EN1 for fewer than 10 and EN2 for 10 or more lymph nodes removed., Results: The median number of positive nodes was 1 (range, 1-32). The largest group was N1 (52.4%), which was followed by N2 (29.6%) and N3 (18%). The median number of EN was 13 (range, 1-73). The patients were allocated to EN1 and EN2 as follows: 31.9% and 68.1%, respectively. The rates of EN2 patients were 62.2%, 72.2%, and 78.2% in N1, N2, and N3, respectively. For all patients, the estimated 5- and 10-year relapse-free survival rates were 41% and 39%, respectively; and the estimated 5- and 10-year overall survival rates were 51% and 42%, respectively. Extension of lymph node excision was found to be not prognostic for relapse and survival (P = 0.55 and P = 0.88, respectively)., Conclusions: Extension of lymph node excision has no impact on relapse and survival of stage III cutaneous melanomas.