Stage IIB Patients Research Articles

Synchronous Boost in Volume-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy for Stage IIb/IIIb Cervical Cancer

There are limited data from retrospective studies regarding whether survival outcomes and toxicity after the dose of parauterine tissue and metastatic lymph nodes simultaneously being increased in Volumetric intensity therapy (VMAT) are equivalent to those after Three-dimensional radiation therapy (3D-CRT) among women with stageIIB (2009 FIGO )/ IIIB (2009 FIGO ) cervical cancer. Analysis of the outcomes including the rate of survival and toxicity among women with stage IIB/IIIB cervical cancer at least 4 years ago. In this trial involving patients (177 patients) with stage IIB (90 patients) or IIIB (87 patients) cervical cancer, we randomly assigned patients to undergo VMAT or 3D-CRT. All patients were treated with concurrent chemoradiotherapy. Cisplatin 40mg/m2/week was selected for chemotherapy and radiotherapy included external beam radiotherapy follow by Intracavitary brachytherapy. VMAT: 45 Gy in 25 fractions to the pelvis, 57.5 to 60GY in 25 fractions to metastatic lymph node, 50GY in 25 fractions to Para-uterine tissue and 56GY in 25 fractions to Parauterine tissue invaded . 3D-CRT: 50Gy in 27 fractions to the pelvis, 60GY in 32 fractions metastatic to lymph node, 50GY in 27 fractions to Parauterine tissue and 56 to 60GY in 30 to 32 fractions to Parauterine tissue invaded. Two groups of external irradiation were used of Intracavitary brachytherapy including six applications of 5.5 to 6Gy each to point ‘A’ . Point ‘A’ EQD2=85-90GY. The shortest follow-up time is 48 months. 90 patients were assigned to VMAT and 87 to 3D-CRT and the mean age of the 177 patients was 52.0 years. Overall, the 4-year overall survival (OS) was 83.6%; The incidences of grade 3-4 gastrointestinal or urinary toxicity were 4.5% and 5.1%; Overall 4-year survival was 90% for stage IIB patients and 77% for stage IIIB patients (p = 0.017). The 4-year survival for all women, the stage of disease, tumor size, the grade of histologic and Lymph node characteristics were of statistical significance (p < 0.05). VMAT was associated with a slightly higher rate of overall survival (OS) or disease-free survival (DFS) than 3D-CRT (4-year rate, 84.4% vs 82.2%; 83.3% vs 80.5%; p > 0.05). VMAT were related with lower incidences of grade 3-4 gastrointestinal and urinary toxicity (p < 0.05) . In this trial, the stage of disease, grade of histologic, tumor size and Lymph node characteristics are independent prognostic factors. Although comparing VMAT with 3D-CRT, the OS, and DFS were Slightly better but No statistically significant differences (p > 0.05) were found between arms. VMAT were related with low The incidences of grade 3-4 gastrointestinal and urinary toxicity (p < 0.05).

The Relevance of Serosal Exposure Without Nodal Metastasis in Resectional Gastric Cancer.

According to 8th AJCC/UICC TNM criteria, stage IIB includes pT1N3M0, pT2N2M0, pT3N1M0, and pT4aN0M0, which includes not only early gastric cancer but also locally advanced cancer. There are currently no data about whether there is any additional impact of serosal exposed cancer without nodal metastasis (pT4aN0) on patients' survival outcomes compared with other subgroups in IIB. Patients who underwent radical gastrectomy for gastric cancer patients were enrolled, including 427 patients in stage IIB; 20 (4.68%), 104 (24.35%), 172 (40.28%), and 131 (30.67%) patients were classified as pT1N3a, pT2N2, pT3N1, and pT4aN0, respectively. Clinicopathological characteristics, recurrence pattern, and survival and recurrence rates were analyzed according to the TNM subgroups. Cancer-specific and relapse-free survival were significantly worse in serosal exposed cancer than in nonserosal exposed cancer in stage IIB (P = 0.019 and P = 0.015). Recurrence rate was highest in the pT4aN0 subgroup (29.0%) in stage IIB, and peritoneal metastasis was the most common pattern. Survival outcomes of the pT4aN0 subgroup were not significantly different from those of the stage IIIA or pT4aN1 subgroups. Patients with serosal exposed cancer without nodal metastasis shows worse cancer specific and disease-free survival with higher incidence of peritoneal metastasis than other subgroups in stage IIB. Further surveillance studies, including staging laparoscopy and active adjuvant therapy, are required in this subgroup of patients.

The predictive value of the prognostic staging system in the 8th edition of the American Joint Committee on Cancer for triple-negative breast cancer: a SEER population-based analysis.

To examine the stage changes and survival differences among triple-negative breast cancer (TNBC) patients based on the prognostic staging system. We used the SEER database to identify eligible patients with TNBC diagnosed between 2010 and 2014. Kaplan-Meier curves were drawn for comparison. The primary end point was breast cancer-specific survival. The median follow-up time was 26 months for 19,608 patients. The stages of all TNBC patients increased or remained unchanged during rearrangement from anatomic staging to prognostic staging. Stage IIA, IIIA and IIIC comprised the majority of patients. Several patients did not have prognostic staging. Stage IIIC incorporated six substages that contributed to high heterogeneity. Overall, the Kaplan-Meier curves still showed the favorable differentiation among stages and substages, with the exception of stage IIB and substage IIIA (T2N0, grade 2-3) patients. The prognostic information for breast cancer patients provided by the novel prognostic staging system may be less accurate for TNBC patients in our independent analysis. Moreover, stage IIB and substage IIIA (T2N0, grade 2-3) should possibly undergo further evaluation.

Age-related survival disparity in stage IB and IIB cervical cancer patients.

Whether young cervical cancer patients have poorer prognosis compared to older ones has remained controversial over the past half century. The last three decades have seen a rise in morbidity and mortality among young Japanese women with cervical cancer. This reflects the fact that the importance of prevention has not been fully recognized due to limited clinical studies. We examined the relationship between age and prognosis in cervical cancer. We retrospectively examined medical records of consecutive patients with International Federation of Gynecology and Obstetrics stage IB and IIB cervical cancer at a hospital in Japan. Patients were divided into two age groups: less than or equal to 39 years (adolescent and young adult [AYA] group) and greater than or equal to 40 years (older adult group). We compared prognosis and clinical factors associated with prognosis between AYA and older adult patients. Data from 182 patients (AYA n = 71; older adults n = 111) treated between 2004 and 2011 were analyzed. The proportion of loss to follow-up was 6.0%. Significant differences were observed in stage and lymph node metastasis between the two groups at baseline. However, despite the older adult group having a higher proportion of advanced cancer patients, the overall survival rate of stage IIB patients in the AYA group at the 3-year follow-up was significantly lower (AYA 53.6%, older adults 86.3%, P < 0.05). Multivariate analysis adjusted for clinical factors revealed that AYA patients had a 3.7-3.9 times greater mortality risk compared to older adults. AYA patients with stage IB and IIB cervical cancer may have a prognostic disadvantage.

Relationship between the semi-quantitative index of 99Tcm-3PRGD2 SPECT/CT imaging and clinical pathological features of breast cancer

Objective To investigate the tumor/non-tumor (T/NT) ratio during 99Tcm-hydrazinonicotinamide(HYNIC)-(poly-(ethylene glycol), PEG)4-Glu(cyclo(Arg-Gly-Asp-D-Phe-Lys(PEG4)))2 (99Tcm-3PRGD2) SPECT/CT imaging and clinical pathological features of breast cancer. Methods Forty-five female patients (age range: 39-76 (53.0±9.5) years) with suspected breast malignant nodules or masses from October 2016 to June 2017 were prospectively enrolled. Patients underwent 99Tcm-3PRGD2 SPECT/CT imaging before breast puncture and surgery. All subjects had pathological results, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER-2), Ki-67 and microvessel density (MVD) were obtained by immunohistochemistry and fluorescence in situ hybridization (FISH). Two-sample t test and Kruskal-Wallis H test were used to analyze the data. Results Invasive ductal carcinoma was pathologically confirmed in 35 of 45 patients. There were 7 patients in stage Ⅰ, 11 patients in stage ⅡA and 17 patients in stage ⅡB. The Luminal A subtype, Luminal B subtype, ERBB2+ subtype, Basal-like subtype were found in 6, 9, 9 and 11 patients, respectively. The T/NT ratio was significantly higher in the stage Ⅱ B patients than that in stage Ⅰ+ ⅡA patients (4.54±1.46 vs 3.32±1.72, t=-2.24, P<0.05). Patients with ERBB2+ subtype had higher T/NT ratio compared to patients with Basal-like subtype: 5.80(3.90, 6.70) vs 2.80(2.20, 3.50), H=11.06, χ2=15.31, both P<0.05. Besides, the T/NT ratios in the HER-2 positive group and lymphatic metastasis group were significantly higher than those in the HER-2 negative group and group without lymph node metastasis (t values: -3.99, -2.51, both P<0.05). MVD of HER-2 positive group was higher than that of HER-2 negative group (t=7.13, P<0.01). Conclusion The T/NT ratio during 99Tcm-3PRGD2 SPECT/CT imaging has relations with TNM staging, lymph node infiltration and HER-2 in breast cancer. Key words: Breast neoplasms; Tomography, emission-computed, single-photon; Tomography, X-ray computed; Arg-Gly-Asp

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

BackgroundCervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC).MethodsA total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis.ResultsThe frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/106 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p < 0.001; p = 0.009). The intensity of HPV E1-specific T cell responses were higher in the stage IIB patients and patients with no pelvic lymph node metastasis (p = 0.038; p = 0.044). Univariate analysis showed that HPV E1 specific T cell response was associated with progression-free survival (PFS) and overall survival (OS) (PFS: p = 0.021; OS: p = 0.004). Multivariate analysis showed that HPV E1-specific T cell response was an independent prognostic factor influencing PFS and OS among all the factors included in our study (PFS: HR = 7.252, 95%CI = 1.690–31.126, p = 0.008; OS: HR = 7.499, 95%CI = 1.661–33.856, p = 0.009). The survival curves showed that the rate of PFS and OS in patients with HPV E1 specific T cell response was significantly higher than those who did not response.ConclusionsOur study demonstrated that the level of HPV E1-specific T cell response was correlated with the survival of advanced patients with CSCC. Patients who displayed no HPV E1-specific T cell response were more likely to be those with poor prognosis.

Propensity Score Analysis of Radical Hysterectomy Versus Definitive Chemoradiation for FIGO Stage IIB Cervical Cancer.

The aim of this study was to compare the outcomes and toxicities of radical hysterectomy (RH) and definitive chemoradiation (CRT) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. A retrospective analysis was performed on FIGO stage IIB patients who underwent RH with adjuvant radiotherapy (surgery group) or intended to receive CRT (CRT group). The distributions of disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Propensity score matching (PSM) was performed for the 2 groups based on age, tumor diameter, histological type, and pelvic node metastasis in pretreatment imaging tests. Median follow-up times were 58 months in the surgery group (n = 75) and 55 months in the CRT group (n = 65). Propensity score matching identified 37 patients with similar characteristics from each group. Significant differences were observed in the ratio of the chemotherapy combination between the surgery and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS rates were slightly higher in the surgery group than in the CRT group before PSM (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five-year OS rates were similar between the surgery and CRT groups before (70% vs 75%, P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate analyses also showed that neither DFS nor OS was associated with the treatment modalities regardless of PSM. The incidence of late toxicities grade 2 or greater was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and after PSM (19% vs 24%, P = 0.78). The results of this study suggest that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer. However, prospective larger studies are needed to confirm this.

18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Breast Cancer in Men.

18F-FDG PET/CT has demonstrated substantial value in systemic staging of newly diagnosed breast cancer in women. However, it is not known whether breast cancer in male patients benefits similarly. This study assesses 18F-FDG PET/CT systemic staging in patients with newly diagnosed male breast cancer and determines detection rates for unsuspected distant metastases stratified by pre-PET/CT stage. Methods: In this Institutional Review Board-approved retrospective study, our Health Care Information System was screened for stage I-III male patients with breast cancer who underwent 18F-FDG PET/CT before systemic or radiation therapy from 2004 to 2017. Initial stage was determined by mammography, ultrasound, or surgery. 18F-FDG PET/CT was evaluated to identify unsuspected extraaxillary regional nodal and distant metastases, and a post-PET/CT stage was determined. Rates of upstaging to stage IV were determined for each initial stage. Results: During the 14-y period, 10,124 unique patients underwent 18F-FDG PET/CT for breast cancer at our institution. Of these, 106 patients were men, and 39 of these patients were imaged at initial staging and met the inclusion criteria. Median age was 62 y (range, 31-90 y), most had ductal carcinoma (95%), and most were estrogen receptor-positive (97%). In 7 of 39 patients (18%), 18F-FDG PET/CT identified previously unsuspected distant metastases, which increased patient stage to IV. This included 3 of 19 (16%) initial stage IIB patients and 4 of 12 (33%) initial stage III patients. 18F-FDG PET/CT also detected an unsuspected synchronous lymphoma in 1 patient. Conclusion:18F-FDG PET/CT revealed previously unsuspected distant metastases in 16% of male patients with pre-PET/CT stage IIB breast cancer and 33% of those with stage III breast cancer. These rates are comparable to previously published upstaging rates in female patients. 18F-FDG PET/CT demonstrates value for systemic staging of male patients with breast cancer and should be considered for use in newly diagnosed patients, particularly those with stage IIB and III disease.

Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront Surgery.

Neoadjuvant chemotherapy (NAC) is increasingly utilized to optimize survival in proximal pancreatic adenocarcinoma. However, few studies have explored the impact of NAC in distal pancreas cancer. Patients with resectable pancreatic adenocarcinoma of the body or tail treated with either upfront pancreatectomy or NAC followed by surgery were identified in the 2006-2014 National Cancer Database. Trends in utilization, predictors of use, and impact of NAC on overall survival were determined. Of 1485 patients, 176 (11.9%) received NAC. Use of NAC increased from 9.3% in 2006 to 16.9% in 2013 [odds ratio 1.14; 95% confidence interval (CI) 1.05-1.24; p = 0.001]. NAC patients were younger, had higher clinical stage, and preoperative CA 19-9 levels (all p < 0.05). After adjustment for patient-, tumor-, and treatment-related factors, increased clinical stage was the greatest independent predictor of neoadjuvant approach (p < 0.001). On multivariable analysis, survival benefit from NAC did not reach threshold of significance (95% CI 0.66-1.04; p = 0.10) for the entire cohort. However, NAC was associated with a significant survival advantage in clinical stage III with a 51% decreased yearly risk of death (adjusted hazard ratio 0.49; 95% CI 0.25-0.98; p = 0.04). A trend towards improved survival with NAC was observed among stage IIA (p = 0.09) and IIB (p = 0.07) patients. Neoadjuvant chemotherapy is associated with improved overall survival in Stage III distal pancreatic adenocarcinoma and shows promise in earlier stage disease. However, only a small percentage of patients receive NAC. Prospective evaluation of NAC in distal pancreatic adenocarcinoma is warranted based on these findings.

Modification of the eight-edition tumor-node-metastasis staging system with N1b for papillary thyroid carcinoma: A multi-institutional cohort study

ObjectivesBased on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort. Materials and methodsThis study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA. ResultsThe mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p < 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p < 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p < 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%. ConclusionThis multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC.

Significance of circulating tumor cells in osteosarcoma patients treated by neoadjuvant chemotherapy and surgery.

PurposeBy examining and identifying circulating tumor cell (CTC) counts and subtypes of peripheral blood in osteosarcoma patients, we evaluated the relationship between CTCs and characteristics of osteosarcoma patients, as well as CTC changes after neoadjuvant chemotherapy and surgery.MethodsCanPatrol™ CTC technology was used to detect CTCs in peripheral blood before and after treatment in 32 osteosarcoma patients. Peripheral blood samples from 10 healthy volunteers were included as controls and examined for the presence of CTCs.ResultsOf the 32 osteosarcoma patients, CTCs were detected in 30 patients before treatment, and the average CTC count was 14.06±9.08. No CTCs were detected in the 10 healthy volunteers. The detected CTCs were divided into epithelial CTCs, mesenchymal CTCs (M-CTCs), and biophenotypic epithelial/mesenchymal CTCs. The average number of pretreatment CTCs was higher in stage III patients than in stage IIB patients (P=0.012). Twenty-eight patients were screened for changes in CTC count at 1 week after neoadjuvant chemotherapy and at 4 weeks after surgery. We divided these 28 patients into two groups according to the changes in the percentage of M-CTCs before and after treatment, and the results showed that the disease-free survival (DFS) was significantly shorter in the M-CTC percentage-increased group than in the M-CTC percentage-decreased or no-change group (P=0.032). Five patients with stage II osteosarcoma were examined for CTCs at the appearance of lung metastases, and the total number of CTCs was found to be higher at the appearance of lung metastases than before treatment in these patients.ConclusionThe rate of presence of CTCs in the peripheral blood of osteosarcoma patients is high, and patients with an increased percentage of M-CTCs after treatment have a shorter DFS. The dynamic monitoring of changes in CTC counts after treatment has clinical significance for the timely detection of recurrence or metastasis.

Curation of the Pancreatic Ductal Adenocarcinoma Subset of the Cancer Genome Atlas Is Essential for Accurate Conclusions about Survival-Related Molecular Mechanisms.

Purpose: Publicly available databases, for example, The Cancer Genome Atlas (TCGA), containing clinical and molecular data from many patients are useful in validating the contribution of particular genes to disease mechanisms and in forming novel hypotheses relating to clinical outcomes.Experimental Design: The impact of key drivers of cancer progression can be assessed by segregating a patient cohort by certain molecular features and constructing survival plots using the associated clinical data. However, conclusions drawn from this straightforward analysis are highly dependent on the quality and source of tissue samples, as demonstrated through the pancreatic ductal adenocarcinoma (PDAC) subset of TCGA.Results: Analyses of the PDAC-TCGA database, which contains mainly resectable cancer samples from patients in stage IIB, reveal a difference from widely known historic median and 5-year survival rates of PDAC. A similar discrepancy was observed in lung, stomach, and liver cancer subsets of TCGA. The whole transcriptome expression patterns of PDAC-TCGA revealed a cluster of samples derived from neuroendocrine tumors, which have a distinctive biology and better disease prognosis than PDAC. Furthermore, PDAC-TCGA contains numerous pseudo-normal samples, as well as those that arose from tumors not classified as PDAC.Conclusions: Inclusion of misclassified samples in the bioinformatic analyses distorts the association of molecular biomarkers with clinical outcomes, altering multiple published conclusions used to support and motivate experimental research. Hence, the stringent scrutiny of type and origin of samples included in the bioinformatic analyses by researchers, databases, and web-tool developers is of crucial importance for generating accurate conclusions. Clin Cancer Res; 24(16); 3813-9. ©2018 AACR.

The Influence Of Obesity in Stage IIB Posterior Tibial Tendon Dysfunction Corrective Surgery

Category: Hindfoot Introduction/Purpose: In the western population prevalence of posterior tibial tendon dysfunction (PTTD) is said to be 3.3% and it is one of the most commonly undiagnosed foot and ankle pathologies. Stage IIB disease according to Johnson and Strom criteria is managed surgically and there are literature demonstrating good clinical outcomes. Obesity being a global epidemic it affects the patient both biomechanically and biochemically. Aim of the study was to investigate the influence of obesity on functional outcome scores, incidence of postoperative surgical site infection (SSI), and repeat surgery after corrective surgery for stage IIB posterior tibial tendon dysfunction (PTTD). Methods: Between January 2007 and December 2013, 102 patients who underwent corrective surgery for stage IIB PTTD at a tertiary hospital were evaluated. We categorized the group with a BMI less than 30 kg/m as control and the group with BMI more than 30 kg/m as obese. The patients were prospectively followed for 2 years. AOFAS mid foot and hind foot scores, mid foot and hind foot VAS scores, SF36 physical and mental function scores were measured pre-operative, post-operative 6 months and post-operative 24 months. SPSS was used for statistical analysis. P value &lt;0.05 was considered as a significant value. Results: 19.6 percent of our study population was obese, there were 38 males and 64 females. The average age of the population was 44.3years and the average BMI for the population was 28.78kg/m2. Clinical outcomes are as follows SF36 physical function score demonstrated statistical significance (p=0.0001, CI -22.20 to -9.80), AOFAS midfoot scores (p=0.82, CI -9.55 to 7.56), AOFAS hindfoot scores (p=0.23, CI -10.60 to 2.60), Midfoot Visual Analogue Scores (p=0.54, CI 0.31 to 0.76), Hindfoot Visual Analogue Scores (p=0.45, CI 0.21 to 0.68) and SF36 mental health scores (p=0.99, CI -5.76 to 7.74) did not demonstrate any significance (6%) in the control group and 10% in the obese group required repeated surgery for complications. Conclusion: Both groups of patients who underwent corrective surgery for stage IIB pttd demonstrated good functional outcomes but there was a significantly higher risk of repeat surgery in the obese group. Obese patients should not be excluded from stage IIB PTTD corrective surgery but patients should be counselled of the higher risk percentage.

Prognostic Implication of N1b Classification in the Eighth Edition of the Tumor-Node-Metastasis Staging System of Differentiated Thyroid Cancer.

Regional lymph node metastases (LNM) have prognostic significance in differentiated thyroid cancer (DTC). However, there was no distinction between N1a and N1b in the final staging classification in the eighth edition of the tumor-node-metastasis (TNM) staging system. This study aimed to evaluate the prognostic implication of N1b classification for predicting disease-specific survival (DSS) in DTC patients with stage I/II disease. A total of 3089 patients with stage I/II DTC who underwent thyroid surgery between 1996 and 2005 were included. DSS was evaluated according to N classification and number of LNM. A modification of the TNM was assessed that classified N1b cases in patients aged ≥55 years as stage IIB and the remaining cases as stage IIA. The mean patient age was 45.6 years, and the median follow-up period was 10.0 years. In patients aged ≥55 years, patients with N1b had significantly poorer DSS compared to those with N0 (hazard ratio [HR] = 11.0; p < 0.001) and N1a (HR = 4.2; p = 0.013). The large-volume LNM group had significantly poorer DSS compared to the N0 (HR = 10.1; p < 0.001) and small-volume LNM (HR = 3.9; p = 0.019) groups. When patients were reclassified using the modified TNM staging system, DSS was significantly poorer in stage IIB patients than in stage IIA patients (HR = 2.9; p = 0.030). N1b classification has a significant prognostic implication in patients with stage I/II DTC, especially in older patients. Modified TNM staging employing N1b classification could be more useful for the prediction of DSS.

A National-Level Validation of the New American Joint Committee on Cancer 8th Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases. The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC. A total of 6651 and 2579 stage IIA (2-5cm) and 1777 and 641 stage IIB (> 5cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p < 0.001). After adjustment for available demographic and clinical confounders, stage IIB was significantly associated with worse survival in both cohorts (hazard ratio 1.58 and 2.01, both p < 0.001). This study validates the new AJCC subclassification of stage II anal cancer into A and B based on size (2-5cm vs. > 5cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

Time to reintroduction of feeding in infants with nonsurgical necrotizing enterocolitis

BackgroundFor infants with necrotizing enterocolitis (NEC) treated nonoperatively, no consensus exists on the optimal fasting period prior to reintroducing feeds after NEC. We report our experience with early (<7days) and late (≥7days) refeeding in this population. MethodsA chart review of infants with NEC born between 2006 and 2016 was performed. Data elements include demographics, comorbidities, day of diagnosis, Bell's stage, recurrence, strictures, length of stay and mortality, and were grouped into early and late refeeding. T-tests were used for means and chi-squared tests for distribution of proportions. Linear and logistic regressions were used to further evaluate the association of length of stay, stricture, recurrence, and death with time to refeeding. ResultsOf 228 NEC patients, 149(65%) were treated nonoperatively (Bell Stages I, IIA, IIB, IIIA). Eleven patients were excluded owing to never restarting feeds, largely secondary to early death. The early (n=40) and late refeeding (n=98) groups were not significantly different with regard to mean gestational age at birth, race, birth weight, day of life at NEC diagnosis, or cardiac disease. NEC Stage was significantly different (p<0.001). The late group had significantly more Stage IIB patients (p=.02), and the early group had more stage I patients (p=<0.01). After adjusting for Bell's stage, the odds of NEC recurrence, death, and the composite outcome of recurrence or stricture or death were not significantly different between early and late groups. ConclusionsNo standardized guidelines exist for restarting enteral nutrition following medical NEC. In patients managed nonoperatively, early reintroduction of feeding was not significantly associated with increased NEC recurrence, mortality, or stricture. Level of evidenceTreatment Study – Level III.

Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications

Epigenetic aberrations are recognized as having pivotal roles in cancer etiology and progression. Histone deacetylases are among the most studied epigenetic modulators in various cancer types. The expression levels of class I histone deacetylase isoforms 1, 2, and 3 in patient-derived primary osteosarcoma cells (6 cases) was investigated, comparing them to normal bone graft-derived osteoblasts (6 cases) using the immunoblotting technique. Expression profiles of histone deacetylases in high-grade osteosarcoma tissue of 89 patients were examined and their association with clinicopathologic parameters and the patient survival was evaluated. Histone deacetylases were immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. Primary osteosarcoma cells expressed higher levels of histone deacetylase 1 and histone deacetylase 2, but lower levels of histone deacetylase 3 compared to benign osteoblasts. Overall, 82, 99, and 93% of 89 osteosarcomas showed nuclear expression of the histone deacetylase isoforms 1, 2, and 3, respectively. Low levels of histone deacetylase 1 were significantly associated with a high Enneking stage (P=0.014) and the presence of initial metastasis (P=0.040), while low levels of histone deacetylase 3 were significantly correlated with age >15 years (P=0.026). Univariate survival analysis found significantly shorter survival in the patients with a high Enneking stage (P<0.001), axial location (P=0.009), presence of initial metastasis (P<0.001), low-histone deacetylase 1 expression (P=0.038), and low-all-histone deacetylases expression (P=0.016). Multivariate survival analysis showed that only axial location (P=0.011) and low-all-histone deacetylases expression (P=0.039) were independent prognostic factors. In subgroup analysis of stage IIB patients (n=45), only axial location and low-all-histone deacetylases expression were associated with shorter survival in both univariate and multivariate analysis (axial location, P=0.008 and 0.010; low-all-HDACs, P=0.013 and 0.038, respectively). Low levels of all-histone deacetylases expression were significantly associated with advanced disease status and short survival. These findings may be a guide to future use of histone deacetylase inhibitors in osteosarcoma patients.

The Role of Surgery in Treating Resectable Limited Disease of Esophageal Neuroendocrine Carcinoma.

Esophageal neuroendocrine carcinoma (NEC) is a rare malignant tumor. The role of surgery in resectable limited disease of esophageal NEC remains unclear. How to select a specific group of limited disease of esophageal NEC who might benefit from surgery remains to be answered. Patients undergoing esophagectomy for resectable limited disease of esophageal NEC in our department from January 2007 to June 2015 were analyzed. TNM staging system was applied to describe those patients, and according to their different long-term prognosis after surgery, those patients were subgrouped into surgery response limited disease (SRLD) group and surgery non-response limited disease (SNRLD) group. Both univariate and multivariate analyses were applied to identify potential prognostic factors. A total of 72 patients with resectable limited disease of esophageal NEC were identified for analysis. The median survival time of those patients was 21.5months. There was no significant survival differences among stage I, stage IIA, and stage IIB patients, but all these patients had significantly longer survival than stage III patients. Therefore, stage I, stage IIA, and stage IIB patients were aggregated together as SRLD group, and stage III patients were aggregated as SNRLD group. SRLD patients obtained significantly longer survival than SNRLD patients in both univariate analysis and multivariate analysis. Moreover, adjuvant therapy could significantly benefit SRLD patients (P=0.004) but could not benefit SNRLD patients (P=0.136). Different responses to surgery existed in resectable limited disease of esophageal NEC indicating the need of further subgrouping for those patients. The resectable limited disease of esophageal NEC could be further subgrouped into SRLD group and SNRLD group according to the TNM staging system.

Auricular vagal nerve stimulation in peripheral arterial disease patients.

Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Prognostic factors of overall survival and cancer-specific survival in patients with resected early-stage rectal adenocarcinoma: a SEER-based study

The benefits of radiotherapy for colorectal cancer are well documented, but the impact of adjuvant radiotherapy on early-stage rectal adenocarcinoma remains unclear. This study aimed to identify predictors of overall...