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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: 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).)

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.

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.

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: 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/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.

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.)

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.)

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.)

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.

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.

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.

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.

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.)

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.

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.

Triple-negative breast cancer (TNBC) subtype is among the most aggressive cancers with the worst prognosis and least therapeutic targetability while being more likely to spread and recur. Cancer transformations profoundly alter cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. Here we confirm that relative to ER-positive cells (MCF7), TNBC cells (MBA-MD-231) rely more on glycolysis thus providing a rationale to target these cells with glycolytic inhibitors. Indeed, iodoacetate (IA), an effective GAPDH inhibitor, caused about 70% drop in MDA-MB-231 cell viability at 20 μM while 40 μM IA was needed to decrease MCF7 cell viability only by 30% within 4 hours of treatment. However, the triple negative cells showed strong ability to recover after 24 h whereas MCF7 cells were completely eliminated at concentrations <10 μM. To understand the mechanism of MDA-MB-231 cell survival, we studied metabolic modulations associated with acute and extended treatment with IA. The resilient TNBC cell population showed a significantly greater count of cells with active mitochondria, lower apoptotic markers, normal cell cycle regulations, moderately lowered ROS, but increased mRNA levels of p27 and PARP1; all compatible with enhanced cell survival. Our results highlight an interplay between PARP and mitochondrial oxidative phosphorylation in TNBC that comes into play in response to glycolytic disruption. In the light of these findings, we suggest that combined treatment with PARP and mitochondrial inhibitors may provide novel therapeutic strategy against TNBC.

Background: A series of studies have assessed the clinicopathological features and prognostic impact of spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) bringing conflicting findings so far. We performed a systematic review and meta-analysis to synthesize the available evidence regarding to the prognostic value of STAS in NSCLCs., Methods: Studies were identified by searching databases including PubMed, EMBASE, Web of Science, and Cochrane Library up to August 2018 without language restrictions. Results of these searches were filtered according to a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines., Results: A total of 3,754 patients from 14 studies were selected for the present study. The pooled results suggested that presence of STAS was associated with worse recurrence-free survival (hazard ratio [HR], 1.975; 95% confidence interval [CI], 1.691 to 2.307; p < 0.001) and overall survival (HR, 1.75; 95% CI, 1.375 to 2.227; p < 0.001) in NSCLCs. Subgroup analysis by histology type indicated the presence of STAS was significantly associated with inferior recurrence-free survival in resected lung adenocarcinoma (n = 7; HR, 2.288; 95% CI, 1.843 to 2.840; I 2  = 7.80%), lung squamous cell carcinoma (n = 3; HR, 1.622; 95% CI, 1.279 to 2.056; I 2  = 0%), and lung pleomorphic carcinoma (n = 1; HR, 4.76; 95% CI, 1.168 to 19.398). Additionally, a number of clinicopathological characteristics indicating STAS in NSCLCs are summarized., Conclusions: Our study indicates that tumor STAS was a potentially significant prognostic predictor for surgical patients with NSCLCs. The prognostic impact of STAS present in the resection margin remains undetermined. Further large-scale prospective studies are warranted to confirm the prognostic significance of STAS in patients with NSCLCs., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Intracranial metastases are the most frequent brain tumor with recurrence rates after treatment of around 40-60%. Age is still considered a determinant of treatment and prognosis in this pathology. Recent studies analyzing the impact of metastasectomy in elderly patients focused on reporting perioperative mortality and morbidity rates but not on the evaluation of oncological outcome parameters. Aim of this study is to determine risk factors for in-brain local recurrence after brain surgery in this sub-population. From October 2009 until September 2016 all patients aged 65 years and above with histopathologically confirmed metastasis after surgical resection were retrospectively studied. Clinical, radiological and perioperative information was collected and statistically analysed. Follow-up consisted of clinical and radiological assessment every 3-months following surgery. 78 patients were included, of these 50% were female (39 patients). Median age was 71 years (66-83). Early postoperative-MRI verified a complete surgical resection in 41 patients (52.6%) and showed a tumor-remnant in 15 patients (19.2%). In 22 patients the MRI result was inconclusive (28.2%). None of the patients experienced severe complications due to surgery. The median postoperative NIHSS was adequate 1 ± 1.4 (0-6), nonetheless, insignificantly improved in comparison to the preoperative NIHSS (p = 0.16). A total of 20 patients (25.6%) presented local recurrence. The only statistically significant factor for development of local in-brain recurrence after resection of cerebral metastases in patients above 65 years of age was a tumor-remnant in the early postoperative MRI (p = 0.00005). Median overall survival was 13 months. Local in-brain recurrence after surgical resection of a cerebral metastasis in patients above 65 years of age was 25.6%. In our analysis, tumor-remnant in early postoperative MRI is the only risk factor for local in-brain recurrence. Oncological parameters in the present cohort do not seem to differ from recent phase III studies with non-geriatric patients. Nevertheless, controlled studies on the impact of metastasectomy in elderly patients delivering high quality reliable data are required.

A 75-year-old person was referred to speech and language therapy for voice rehabilitation following diagnosis of unilateral vocal cord palsy, secondary to relapsed non-small-cell lung cancer. On assessment, the patient presented with moderate-severe dysphonia. In addition, they presented with moderate pharyngeal stage dysphagia with risk of silent aspiration, which was successfully managed using a simple head turn strategy. This presentation is not atypical for patients who have disease in the upper chest or mediastinum and an increase in awareness and anticipation of such symptoms, with timely referral to appropriate specialist services, could help prevent complications associated with dysphagia, such as aspiration pneumonia and worse quality of life., Competing Interests: Competing interests: Not declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

There is controversy regarding the surgical route selection for tuberculum sellae meningiomas (TSMs): the transsphenoidal (TS) or transcranial (TC) approach? We conducted a systematic review and meta-analysis to compare clinical outcomes and postoperative complications between two surgical approaches. Literature search was performed. Relevant articles were selected and evaluated. Data were extracted and analyzed. Eight articles comprising 550 patients met the inclusion criteria. Traditionally, the rates of gross total resection, tumor recurrence, visual improvement, and cerebrospinal fluid leakage were the most common outcomes of interest. We demonstrated that the TS approach was significantly associated with better visual outcomes but more frequent cerebrospinal fluid leakage, while the rates of tumor resection and recurrence showed no significant difference between groups. In addition to surgical results that were consistent with previous studies, we further evaluated the impact of approach selection on common postoperative complications, which were closely related to the recovery course and quality of life. We revealed that the risk of dysosmia was significantly higher in the TS group. There was no significant difference between groups regarding infection, intracranial hemorrhage, and endocrine disorders. Because of the relatively low evidence levels of included retrospective studies, it was difficult to reach a categorical conclusion about the optimal surgical approach for TSMs. Finally, we recommended that the TS approach was an alternative option in patients with smaller TSMs (<30 mm) and limited invasion of optic canals in experienced neurosurgical centers.

In patients with gliomas, changes in hemispheric specialization for language determined by magnetoencephalography (MEG) were analyzed to elucidate the impact of treatment and tumor recurrence on language networks. Demonstration of reorganization of language networks in these patients has significant implications on the prevention of postoperative functional loss and recovery. Whole-brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 patients with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index (LI), a measure derived from the task. The initial scan was performed prior to resection; patients subsequently underwent surgery and adjuvant treatment. A second scan was performed upon recurrence prior to repeat resection. The relationship between the shift in LI between scans and demographics, anatomic location, pathology, and adjuvant treatment was analyzed. Laterality shifts were observed between scans; the median percent change was 29.1% across all patients. Laterality shift magnitude and relative direction were associated with the initial position of language dominance; patients with increased lateralization experienced greater shifts than those presenting more bilateral representation. A change in LI from left or right to bilateral (or vice versa) occurred in 23.3% of patients; complete switch occurred in 5.5% of patients. Patients with tumors within the language-dominant hemisphere experienced significantly greater shifts than those with contralateral tumors. The majority of patients with glioma experience shifts in language network organization over time which correlate with the relative position of language lateralization and tumor location., (© 2018 Wiley Periodicals, Inc.)

Background: More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer., Methods: We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a "Mixed Methods Design", in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients' experiences before, during and after chemotherapy., Discussion: The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.

Objective: Peri- and postoperative time course of meningioma patients who had undergone surgical treatment was evaluated to determine prognostic factors of neurological outcome by focusing on preoperative parameters., Material and Methods: A retrospective monocenter analysis was performed including patients who were operated in the Department of Neurosurgery, University Hospital Leipzig, from 2009 to 2015. Data from all patients with histologically confirmed diagnosis of intracranial meningioma treated microsurgically were included in the study. The individual characteristics of the patients, meningiomas and Karnofsky Performance scores (KPS) were analyzed by multivariate tests., Results: Two hundred ninety-four patients with a median age of 61 years (range: 17-89) were included. Preoperative KPS (p < 0.001), skull base as tumor origin and tumor size (p < 0.05) proved to be significantly strong prognostic factors of KPS deterioration one year postoperative by multivariate analysis. According to uni- and bivariate analysis, the following prognostic factors could also be found: preoperative mass displacement, preexisting recurrence and presence of preoperative symptoms. In this study, age had no significant influence on deterioration in patient health state, measured by KPS, one year postoperative., Conclusion: Patients generally obtained an improvement in KPS score after microsurgical treatment. The knowledge of prognostic factors can be very helpful in the decision-making process for meningioma treatment of the elderly, particularly to estimate the postoperative outcome and quality of life., Competing Interests: The authors have declared that no competing interests exist.

A 90-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed a lesion with multiple nodules covered with abundant mucus at the hepatic flexure. Computed tomography showed a dilated appendix attached distally to the hepatic flexure. Right hemicolectomy was performed, and the pathological examination revealed a mucinous appendiceal adenocarcinoma infiltrating the hepatic flexure without pseudomyxoma peritonei. The patient is doing well without recurrence 12 months postoperatively. Extraperitoneal drainage of the malignant ascites caused by the fistula may allow for an early diagnosis, while also making it possible to successfully resect the lesion, thus resulting in a favorable outcome.

Background: We examined survival and time until recurrence of disease by multivariant analysis in patients treated for papillary thyroid carcinoma (PTC)., Patients and Methods: In the period from January 2003 to January 2018, we analyzed 102 patients with PTC in Public Health Institution-Hospital "Sveti Vracevi" in Bijeljina. Survival and time until recurrence of the disease were analyzed using patients' general data and factors based on preoperative, intraoperative and postoperative examinations. Many prognostic factors were analyzed together; the AGES prognostic score, consisting of age, grade, extent and size, and the AMES prognostic score, consisting of age, metastases, extent and size., Results: We analyzed 102 patients with PTC. Out of these 87 patients had AGES p.s ≤ 3.99 and 15 patients had AGES p.s> 4. The survival of patients was affected by the presence of distant metastases at the time of diagnosis p = 0.00109 and age p = 0.0436. Recurrence of the disease was recorded in 14 patients. Most patients had recurrence of the disease in the first 5 years after initial surgery. Analyzing the time until recurrence, we concluded that, statistically speaking, AGES p.s> 4 affect recurrence of the disease p = 0.0355 in a significant way, while distant metastases affect it in a very significant way (p = 0.008)., Conclusions: Prognostic factors of papillary thyroid carcinoma can be divided into 4 categories, patients' general data and factors based on preoperative, intraoperative and postoperative examinations.

A 37-year-old Hispanic man with a right atrial intracardiac mass diagnosed as diffuse large B-cell lymphoma (DLBCL) was successfully treated with surgery and chemotherapy. During 4 years, several total-body positron emission tomography and MRI scans showed no extracardiac lymphoma. On year 5 after the cardiac surgery, patient presented with sleepiness, hyperphagia, memory loss, confabulation, dementia and diabetes insipidus. Brain MRI showed a single hypothalamic recurrence of the original lymphoma that responded to high-dose methotrexate treatment. Correction of diabetes insipidus improved alertness but amnesia and cognitive deficits persisted, including incapacity to read and write. This case illustrates two unusual locations of DLBCL: primary cardiac lymphoma and hypothalamus. We emphasise the importance of third ventricle tumours as causing amnesia, confabulation, behavioural changes, alexia-agraphia, endocrine disorders and alterations of the circadian rhythm of wakefulness-sleep secondary to lesions of specific hypothalamic nuclei and disruption of hypothalamic-thalamic circuits., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Spread through air spaces (STAS) identified in lung cancer is considered to be a risk factor for recurrence after surgery. The purpose of this study is to clarify the prognostic impact of STAS in sublobar resections., Methods: We studied 514 patients with clinical stage IA cancers: 329 underwent lobectomies and 185 underwent sublobar resections. We assessed the prognostic impact of STAS in the cases with a sublobar resection for stage IA lung cancer versus the cases with a lobectomy., Results: STAS was found in 73 of 329 (22.2%) lobectomy cases and 31 of 185 (16.8%) sublobar resection cases. For overall survival, univariate analysis revealed that STAS was not a prognostic factor in the lobectomy group, but it was a significantly worse prognostic factor for the sublobar resection group in both univariate and multivariate analyses. For the recurrence-free rate, multivariate analysis showed STAS was not a risk factor in the lobectomy group, but it was a significant risk factor for the sublobar resection group in both univariate and multivariate analyses. Patients with STAS and sublobar resection had a significantly higher rate of pulmonary metastases than did patients with STAS and lobectomy (8 of 31 [25.8%] vs 6 of 73 [8.2%])., Conclusions: STAS is a prognostic factor of poor outcomes for sublobar resection in patients with lung cancer. The worse prognosis for sublobar resection would be associated with STAS., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Cervical cancer is one of the most common female malignancies in the world. The ubiquitin-specific protease 8 (USP8) functions by removing ubiquitin from protein substrates, and its potential role in cancer development was recently uncovered in lung cancer. The aim of this study was to investigate the expression and function of USP8 in cervical squamous cell carcinoma (CSCC). MATERIAL AND METHODS Immunohistochemical staining and quantitative PCR were performed to explore the expression of USP8 in both CSCC tissues and adjacent normal cervical tissues. Univariate and multivariate analyses were conducted to evaluate the clinical significance of USP8 in CSCC. Proliferation, migration, and invasion abilities of 2 CSCC cell lines were assessed after overexpression or silencing USP8, respectively. RESULTS Both the RNA and protein levels of USP8 were upregulated in CSCC tissues compared to normal cervical tissues. High expression of USP8 was correlated with advanced tumor stage and high recurrence risk. Moreover, USP8 was identified as a novel independent prognostic factor for CSCC patients. Cellular studies showed that USP8 can enhance the proliferation, migration, and invasion abilities of CSCC cells, thereby promoting tumor progression. CONCLUSIONS High expression of USP8 is frequent in CSCC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting USP8 may be a novel direction for drug development for CSCC therapy.

Rationale: Chordomas are malignant neoplasms derived from incomplete regression of notochordal tissue along the craniococcygeal axis.It is rare for Chordoma arising from the lumbar spine and the traditional long-term prognosis is typically poor., Patient Concerns: The persistent pain in the left side of the waist about 2 years., Diagnoses: Chordoma., Interventions: The patient was treated with surgical resection of the total tumor, followed by the spinal internal fixation of L1 to L2 with pedicle screws., Outcomes: After 5 month follow-up,we find the recurrence in the original lesion.At the 15 month follow-up,the patient was dead after a lot of times revisit by various doctor., Lessons: So It is suggest that the diagnosis should be carried out accurately at the early stage, the lesions and source of lesions should be cut away as broadly as possible, also the radiation and chemotherapy should be carried out after the operation as necessary.

Background: The purpose of this study is to establish whether the lymph node metastases of the papillary thyroid carcinoma are a significant factor in recurrence of the disease by analyzing the time until recurrence of the disease and frequency of recurrence of the disease., Methods: From 1 January 1995 until 30 June 2017, 102 patients were treated at the Public Health Institute Hospital "Sveti Vracevi" in Bijeljina for PTC. In all patients, surgery of the thyroid gland and/or lymph nodes of the neck was performed. Total thyroidectomy (TT) was performed in 20 patients and near-total thyroidectomy leaving <1 g thyroid tissue adjacent to the recurrent laryngeal nerve in 7 patients. TT and lymph nodes dissection were performed in 71 patients. Palliative surgery and biopsy due to locally advanced disease were performed in 3 patients., Results: In our study, 102 patients with PTC were analyzed. 82 patients experienced pure PTC (80.4%), the other 20 patients (19.6%) experienced other variants of PTC. 24 patients (23.5%) experienced multi centric or bilateral tumors. 71 patients (69.6%) experienced histologically verified metastases in the lymph nodes of the neck. 7 patients (6.8%) experienced distant metastases. 20 patients underwent total thyroidectomy (TT), and 7 near-total thyroidectomy. Total thyroidectomy + dissection of central and lower jugular lymph nodes with frozen section histopathology verification was performed in 71 patients (69.6%). Out of these 71 patients, in 50 patients (70.4%) metastases were verified in the lower jugular lymph nodes. A modified lymph node dissection (MRND) was also performed in these patients., Conclusion: Lymph node metastases of the papillary thyroid carcinoma are a plausible prognostic factor. They are important for recurrence of the disease, but not for survival.

The patient database at the First Department of Internal Medicine in Martin, the Central Slovak Institute for Cardiac and Vascular Diseases in Banska Bystrica, and the National Slovak Institute of Cardiovascular Diseases in Bratislava was searched to identify patients with benign tumors of the heart seen during the 5-year period between 2011 and 2016. Forty-one patients with primary cardiac myxomas were identified and their medical records were reviewed for details pertaining to presenting symptoms, staging modalities, treatment approaches, and outcomes. Most of the studied patients were diagnosed with echocardiography ( n = 35, 85%). The occurrence of the tumor was higher in the female population ( n = 25, 61%). The most common presenting symptoms were dyspnoea ( n = 17, 42%), chest pain ( n = 3, 7%), or pain and paraesthesia of the limbs ( n = 2, 5%). Acute embolic event due to embolization of tumor fragments resulted in cerebral stroke ( n = 5, 12%). All patients were treated by resection. Only one comorbid patient died due to multiple-organ dysfunction syndrome two weeks after the resection. The most common postoperative complication was bleeding ( n = 2, 5%) and infection ( n = 2, 5%). The early diagnosis and appropriate treatment are often curative, with very low risk of recurrence. Postoperative survival is high.

The objective of this article is to discuss the pathophysiology, diagnosis, differential diagnosis, and therapy of vulvar leiomyoma. We performed a review of all English-language reports of vulvar leiomyoma published in PubMed from 1978 to 2015 using the following search terms: "vulval leiomyoma," "vulvar leiomyoma," "vulval smooth muscle tumor," and "external genitalia smooth muscle tumor." Vulvar leiomyomas, which are rare benign monoclonal tumors, most commonly occur in the fourth and fifth decades of life. The genetics of vulvar leiomyoma remain undefined. Three principal histological patterns have been identified: spindled, epithelioid, and myxoid. Imaging tests such as ultrasound, endoscopic ultrasound, and magnetic resonance imaging are used in diagnosis. Surgical excision is the only curative treatment for vulvar leiomyomas. Establishment of a full differential diagnosis list and correct final diagnosis before surgery are essential for optimal clinical management. Although recurrence of vulvar leiomyoma is extremely rare, long-term follow-up of all cases is advisable.

Background: Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management., Methods: A total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital., Results: The 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v + vs. v-, 36.5% vs. 47.4%, P = 0.034, HR 1.82, 95% CI: 1.01-3.37). Venous invasion also predicted a shorter overall survival (OS) (v + vs. v-, 33.7% vs. 50.4%, P = 0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v + GC than those without (P = 0.022)., Conclusions: Stage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes.

Background: Whether hepatic resection (HR) could be performed for patients with Barcelona Clinic Liver Cancer (BCLC) B/C stage hepatocellular carcinoma (HCC) is controversial, and the safety and clinical value of HR combined with antiviral therapy for hepatitis B virus (HBV)-related HCC with BCLC-B/C stage remain to be investigated., Methods: We retrospectively evaluated 126 patients with BCLC stage B/C HCC who underwent HR. These patients were divided into the antiviral group (Group A, n = 86) and the control group (Group B, n = 40). The operative indications and prognosis of 126 patients were analyzed., Results: The 1-year, 3-year, and 5-year disease-free survival (DFS) rates for Group A and Group B were 55.4%, 36.1%, 33.7% and 53.8%, 28.2%, 23.1%, respectively. The corresponding overall survival (OS) rates for the two groups were 89.2%, 61.4%, 45.8% and 82.1%, 48.7%, 33.3%, respectively. The DFS and OS for Group A were better than for Group B (p = 0.013, and p = 0.038, respectively). Antiviral therapy was an independent protective factor of late tumor recurrence [hazard ratio (HR) = 0.391, 95% confidence interval (CI): 0.190-0.806, p = 0.011] but not of early tumor recurrence., Conclusion: It is safe and feasible to perform HR combined with antiviral therapy for HBV-related HCC with BCLC stage B/C., (Copyright © 2016. Published by Elsevier Taiwan.)

Physical activity is emerging from epidemiologic research as a lifestyle factor that may improve survival from colorectal, breast, and prostate cancers. However, there is considerably less evidence relating physical activity to cancer recurrence and the biologic mechanisms underlying this association remain unclear. Cancer patients are surviving longer than ever before, and fear of cancer recurrence is an important concern. Herein, we provide an overview of the current epidemiologic evidence relating physical activity to cancer recurrence. We review the biologic mechanisms most commonly researched in the context of physical activity and cancer outcomes, and, using the example of colorectal cancer, we explore hypothesized mechanisms through which physical activity might intervene in the colorectal recurrence pathway. Our review highlights the importance of considering pre-diagnosis and post-diagnosis activity, as well as cancer stage and timing of recurrence, in epidemiologic studies. In addition, more epidemiologic research is needed with cancer recurrence as a consistently defined outcome studied separately from survival. Future mechanistic research using randomized controlled trials, specifically those demonstrating the exercise responsiveness of hypothesized mechanisms in early stages of carcinogenesis, are needed to inform recommendations about when to exercise and to anticipate additive or synergistic effects with other preventive behaviors or treatments.

A 13-year-old male patient with a history of pre-B cell acute lymphoblastic leukaemia (ALL) with isolated central nervous system relapse on maintenance chemotherapy presented with severe thrombocytopenia refractory to platelet transfusions. The patient showed only modest responses to two courses of intravenous immunoglobulin and steroids. He was found to be positive for cytomegalovirus (CMV) with modest viral load. His thrombocytopenia normalised with rituximab therapy and CMV treatment supporting the diagnosis of CMV-associated immune thrombocytopenic purpura (ITP). Following treatment, the patient continued to have a stable platelet count well above the threshold for transfusions. He continued to be intermittently treated for CMV when viral loads became detectable. This report discusses the unique management considerations of ITP in a patient undergoing therapy for ALL with a review of previously reported cases and discusses the possibility of CMV viraemia as a modulating factor., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Ovarian cancer recurs in most patients, with a 5-year survival rate less than 30%. Quality of life is an increasingly important issue in patients with cancer, but there are limited data in women with recurrent ovarian cancer in this regard., Materials and Methods: We used an ad hoc questionnaire to compare changes in health perceptions, burden of disease, and expectations for the future quality of life in women with and without recurrence of ovarian cancer. A total of 173 women were included, 116 with relapse and 57 without, undergoing follow-up in a routine clinical setting., Results: Substantial differences were seen in self-assessed health status between women with and without recurrence; 33.6% and 82.4% of women with and without recurrence rated their health as good to excellent, respectively. More patients with recurrence of disease reported limitations in moderate activity than those without. Furthermore, 79.0% of women without recurrence reported that pain did not affect or only slightly affected daily activities, compared with 28.2% with recurrence. Most women with recurrence (59.5%) reported that they were able to do less than they wanted to because of their emotional status compared with only 15.8% of women without recurrence. In addition, 66.4% of women with recurrence referred that they had problems concentrating at work and home versus 26.3% of women without recurrence., Conclusions: From this survey, it is clear that relapse of disease has a negative psychological and physical impact, highlighting the importance of time without recurrence and the need for effective treatment in the long term.