Independent Assessment of the Children's Hepatic Tumors International Collaboration Risk Stratification for Hepatoblastoma and the Association of Tumor Histological Characteristics With Prognosis.

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.

Post-recurrence survival in patients with cervical cancer.

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.

Degradation of skeletal mass in locally advanced oesophageal cancer between initial diagnosis and recurrence.

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 cm2/m2, respectively; P < 0.001) and decreased body mass index (BMI) (27.9 vs. 26.3 kg/m2, respectively; P = 0.05), but fat mass was increased (68.9 vs. 72.0 cm2/m2, 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.

Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer.

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.

Ovarian reserve and recurrence 1 year post-operatively after using haemostatic sealant and bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy.

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.

The significance of post-radiotherapy parametrial involvement and the necessity of parametrial resection in locally-recurrent or persistent cervical cancer developed after radiotherapy.

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.

Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage III colorectal cancer.

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.

A machine learning-based predictor for the identification of the recurrence of patients with gastric cancer after operation.

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.

Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.

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).

Multiple measures of muscle function influence Sorensen Test performance in individuals with recurrent low back pain.

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.

Feasibility of limited resection for peripheral small-sized non-small cell lung cancer: a retrospective single-center-based study.

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.

Predictors of Stricture and Swallowing Function Following Salvage Laryngectomy.

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.

De novo and recurrent malignancy.

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.

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer.

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.

Preoperative Evaluation of Myxofibrosarcoma: Prognostic Value and Reproducibility of Different Features on MRI.

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.

Oncological and Reproductive Outcomes of Abdominal Radical Trachelectomy.

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.

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab.

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.

Feasibility and effectiveness of palliative intensity-modulated radiotherapy for carotid sinus syndrome secondary to recurrent head and neck cancer.

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.

Three Cases of Ampullary Neuroendocrine Tumor Treated by Endoscopic Papillectomy: A Case Report and Literature Review.

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.