Positive Node Status Research Articles

Evaluation of cystoprostatectomy on patients with prostate cancer extending to bladder: a retrospective study from single center

BackgroundThis is an exploratory research of cystoprostatectomy (CP) in treating prostate cancer (PCa) extending to the bladder, which aimed to evaluate the effects of CP on survival outcomes and improving quality of life (QoL) in these patients.MethodsA total of 27 PCa patients extending to the bladder were subjected to CP and followed up at regular intervals in our center. Prostate cancer-specific survival (PCSS) and prostate-specific antigen recurrence-free survival (PFS) were assessed by Kaplan–Meier analysis. Multivariate Cox regression was performed to evaluate clinical characteristics predicting survivals. QoL and pelvic symptoms were also evaluated.ResultsMedian PCSS was not reached over the period of follow-up. 5-year PCSS rate was 82.1%. Median PFS was 66.0 months. 5-year PFS rate was 58.5%. Multivariate analysis showed Gleason score (≥ 8) (hazard ratio (HR) 2.55, 95% confidence interval (CI) 1.28–4.04, p = 0.033), positive local lymph node status (HR 3.52, 95% CI 1.57–7.38, p = 0.006) and bladder muscle-invasion (HR 4.75, 95% CI 1.37–7.53, p < 0.001) were independent predictors of worse PCSS. The number of patients suffering pelvic symptoms was significantly decreased, and QoL scores were significantly down-regulated after surgeries.ConclusionCP offered effective and durable palliation in patients of locally advanced prostate cancer with invasion of the bladder, providing better QoL and relieving local symptoms.

Association between neutrophil-lymphocyte ratio and lymph node metastasis in gastric cancer: A meta-analysis.

Introduction and Aim:The prognostic role of neutrophil to lymphocyte ratio (NLR) has been explored extensively in the literature. The aim of this meta-analysis was to evaluate the link between NLR and lymph node metastasis in gastric cancer. A method for increasing specificity and sensitivity of pre-treatment staging has implications on treatment algorithms and survival.Search Strategy:The relevant databases were searched as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. After selection, 12 full text articles that met the inclusion criteria were included for quantitative analysis. 2 × 2 squares were generated using lymph node positive/negative, and NLR high/low data. The effect size for each study was calculated using the DerSimonian–Laird random effects model. P values were calculated using the chi-square method. Finally publication bias was evaluated. All statistics were calculated using R Studio.Results:Meta-analysis showed a 1.90 times (odds ratio, with 95% CI 1.52–2.38) increase in risk of positive lymph node status with high neutrophil to lymphocyte ratio. This has significant implications for cancer screening and staging, as NLR is a highly reproducible, cost-effective, and widely available prognostic factor for gastric cancer patients. Additionally, high or low NLR values may have implications for management pathways. Patients with lymph node metastasis can be offered neoadjuvant chemotherapy, avoiding salvage therapy in the form of adjuvant chemoradiotherapy, which is poorly tolerated.Conclusion:This meta-analysis shows an association between NLR and positive lymph node status in gastric cancer patients with implications for staging, as well as preoperative personalisation of therapy.

A comparison of Chinese multicenter breast cancer database and SEER database

There are different characteristics of BC in developing countries and developed countries. We intended to study the factors which influence the survival and prognosis of BC between southern China and the United States. (a) To study the two groups BC patients in southern China from 2001 to 2016 and SEER database from 1975 to 2016. (b) To register, collect and analyze the clinicopathological features and treatment information. Our study found that there are significant differences in tumor size, positive lymph node status and KI-67 between southern China and SEER cohort (P < 0.000). The positive lymph node status may be one of the causes of difference of morbidity and mortality of BC patients in China. Furthermore, the differences in treatment methods may also account for the differences between China and seer databases.

Lymph node distribution in patients with remnant gastric cancer.

Remnant gastric cancer (RGC) is defined as a carcinoma that develops in the gastric remnant from 5years after gastrectomy, regardless of the primary gastric disease. The pattern of lymph node dissemination in these patients is not well understood. The present study aims to understand the lymph node distribution of patients with RGC in a single center. In a total of 1380 patients with gastric cancer, between 1998 and 2020, 43 patients operated on for RGC were analyzed. The pattern of lymph node dissemination was evaluated based on the number of dissected lymph node stations, the number of positive lymph node stations, the positivity index at each analyzed station, the number of dissected lymph nodes per patient, and the positivity index per lymph node station. A mean of 13.0 ± 8.1 lymph nodes were dissected. The incidence of lymph node involvement by dissected station was higher at Stations 19, 11p, 3, 4sb and 7 (50, 40, 37.5, 36 and 31.7%, respectively). Among the positive dissected stations, Station 3 with 52.2%, 4sb with 39.1% and 4sa with 34.8% were the most affected. There was no predilection for lymph node involvement when comparing the lesser and greater gastric curvature. The dissection of Stations 3, 4sb and 4sa is fundamental in surgical treatment with curative purposes. The totalization of gastrectomy with lymphadenectomy of the perigastric and supra-pancreatic stations should be the surgery of choice.

A Model to Identify Candidates for Lymph Node Dissection Among Patients With High-Risk Endometrial Endometrioid Carcinoma According to Mayo Criteria.

BackgroundThe Mayo criteria are the most widely accepted algorithm for predicting the risk of lymph node metastasis in endometrial endometrioid carcinoma (EEC). However, the clinical value of these criteria in high-risk patients is limited and inconclusive.MethodsA total of 240 patients with EEC meeting the Mayo high-risk criteria between January 1, 2015, and December 31, 2018 were included in our study. We retrospectively collected the laboratory reports, basic clinical information, clinicopathological and immunohistochemistry (IHC) findings, and the sequences of molecular pathological markers of these patients. A nomogram for predicting the likelihood of positive lymph node status was established based on these parameters.ResultsAmong the 240 patients, 17 were diagnosed with lymph node metastasis. The univariable analyses identified myometrial invasion >50%, aberrant p53 expression, microsatellite instable (MSI), and cancer antigen 125 (CA125) ≥35 U/ml as potential risk factors for lymph node metastasis. The multivariable analyses showed that aberrant p53 expression, MSI, and CA125 ≥35 U/ml were independent predictors of lymph node metastasis. The area under the curve (AUC) for the nomogram was 0.870, as compared to 0.665 for the Mayo criteria.ConclusionsOur novel prediction model effectively identifies patients at high risk for lymphatic metastasis. This model is a promising strategy for personalized surgery in patients with high risk according to the Mayo criteria.

Invasive IPMN relapse later and more often in lungs in comparison to pancreatic ductal adenocarcinoma

BackgroundThe different oncological outcomes of invasive intraductal papillary mucinous neoplasm (I-IPMN) and pancreatic ductal adenocarcinoma (PDAC) are debated. This study aimed to compare disease recurrence patterns and histopathological characteristics in patients with resected I-IPMN and PDAC. MethodsConsecutive patients undergoing surgical resection for stage I-III I-IPMN or PDAC between 2010 and 2016 were retrospectively analyzed. Patients treated with neoadjuvant therapy or resected for Tis neoplasia were excluded. All surgical specimens were re-staged according to AJCC-8th-edition. ResultsA total of 330 patients were included, of whom 43 had I-IPMN and 287 had PDAC. Median follow-up time was 26.7 (1.3–92.3) months and estimated median disease-free survival (DFS) was 60.3 months (47.2–73.4) for I-IPMN and 23.8 (19.3–28.2) months for PDAC (p < 0.001). During follow-up, 32.6% of I-IPMN and 67.9% of PDAC patients experienced recurrence (p < 0.001). The sites of first recurrence were the lungs (38.5% vs 13.1%, p = 0.027), liver (28.6% vs 45.0%, p = 0.180) and local (15.4% vs 36.6%, p = 0.101) for I-IPMN and PDAC, respectively. At multivariate analysis, I-IPMN histology remained an independent predictive factor for longer DFS (OR 0.528, CI 95% 0.278–1.000, p = 0.050), regardless of stage or adjuvant chemotherapy. I-IPMN and PDAC differed in rates of neuroinvasion (51.2% vs 97.2%) and positive lymph node status (N+) (46.5% vs 82.7%), especially in patients with lower T status. ConclusionI-IPMN showed a different recurrence pattern compared to PDAC, with a higher lung tropism, and longer DFS. This different biological behavior is associated with lower rates of neuroinvasion and nodal involvement, especially in early-stage disease.

Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).

e12622 Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m2, cyclophosphamide 600mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m2, trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.

Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.

516 Background: The incidence of triple negative breast cancer (TNBC) is higher among Black or African American (AA) women, yet AA patients (pts) are underrepresented in clinical trials, exemplifying racial disparity in oncology. We conducted a phase I/II trial to assess the safety and efficacy of durvalumab concurrent with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) neoadjuvant therapy for stage I-III TNBC. The primary efficacy endpoint was pathologic complete response (pCR; ypT0/is,N0) rate. Given the unclear efficacy and safety of immunotherapy in AA pts with breast cancer, we extended our accrual to recruit AA pts, with the goal of evaluating the association between racial groups and PD-L1 expression, stromal tumor infiltrating lymphocytes (sTILs), toxicities, treatment response and survival. Methods: Our study population included 67 pts. PD-L1 immunohistochemistry results and sTIL counts were available on 59 and 60 pts, respectively. Chi-Squared test was used to evaluate associations between race and baseline characteristics. Cox proportional hazards model was used to assess association between AA race and overall survival (OS) and event free survival (EFS), adjusting for age, comorbidities and pCR status. Multivariate logistic regression analyses were used to evaluate the association between race and pCR, development of immune-related adverse events (irAEs) and breast cancer recurrence. Results: Twenty-one pts (31%) self-identified as AA. No significant associations between AA race and baseline body mass index (BMI; p=0.075), Charlson comorbidity index (p=0.32), tumor stage (p=0.40), grade (p=0.54), PD-L1 status (0.92) and sTIL count (p=0.57) were observed. pCR rates did not significantly differ between AA and non-AA pts: 9/21 (43%) AA vs. 22/48 (48%) non-AA (p=0.71). 3-yr OS was 87% in the non-AA versus 81% in the AA cohort (HR 1.72, 95% CI 0.481-6.136; p=0.405); 3 yr EFS were 78.3% and 71.4% in non-AA and AA pts respectively. (HR 1.451, 95% CI 0.524-4.017; p=0.474). Pts with pCR were more likely to remain event-free at 3 yrs, irrespective of race (HR 0.234, 95% CI 0.066-0.829; p=0.024). In multivariate logistic regression analyses, lack of pathologic response (OR for pCR 0.17, 95% CI 0.03-0.7; p=0.02) and node positive status (OR 4.13, 95% CI 1.05-19.88; p=0.05) were associated with recurrence. The incidence of irAEs was similar between AA and non-AA pts and no significant associations were found between irAEs and pathologic response. Conclusions: pCR rates after neoadjuvant immunotherapy and chemotherapy were similar in AA and non-AA pts. Stromal TILs, PD-L1 status, 3yr OS and EFS, and the frequency of irAEs were also similar. These results suggest that when patients receive identical treatment and are monitored closely, disparities in outcomes can be mitigated or abolished. Clinical trial information: NCT02489448.

Correlation of Ki67 working group prognostic risk categories with oncotype DX recurrence score (RS) in early breast cancer (EBC).

553 Background: The 21-gene RS (Oncotype DX) provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative EBC. Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC). The International Ki67 Working Group (IKWG) has provided guidelines for clinical use of Ki67 for prognostic classification (PMID: 33369635). The objectives of this study were to determine the correlation between IHC-measured Ki67 with the 21-gene RS, and evaluate their association with other anatomic and biologic tumor features. Methods: We performed a retrospective chart review of women with HR-positive, HER-2 negative EBC with 0-3 positive lymph nodes who had both Ki67 (via IHC using MIB-1 antibody on surgical specimen at our institutional pathology CLIA laboratory) and 21-gene RS between 2013 to 2021. Patients were categorized into Ki67 low (≤ 5%), intermediate (6-29%), and high (≥30%) based on IKWG recommendations. Overall and risk stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. Linear regression was used to test for associations between tumor features of ER%, PR%, and tumor size and log transformed Ki67 and RS. A t-test was used to compare average log transformed Ki67 and RS by tumor differentiation and nodal status. Results: We identified 461 patients with HR-positive BC of whom 26.7% were ≤ 50 years at diagnosis, 30% pre-menopausal and 10% node-positive. Overall, 29% (n = 137) of patients had low Ki67, 49% (n = 227) intermediate, and 21% (n = 97) high Ki67. 18% (n = 85) had RS 0-10, 67% (n = 311) had RS 11-25 and 14% (n = 65) had RS ≥ 26. There was no significant agreement (kappa &lt; 0) between Ki67 and RS (Kappa = -0.0035, p = 0.5406) in the overall population and fair agreement (kappa 0.21-0.40) between high Ki67 and RS (Kappa = 0.2510, p &lt; 0.0001). Higher ER% was significantly associated with lower RS (p &lt; 0.0001) and lower Ki67 (p = 0.0042). High tumor grade was associated with higher RS and higher Ki67 (p &lt; 0.0001). Higher PR% was associated with lower RS (p &gt; 0.0001) but not lower Ki67. Positive nodal status and larger tumor size were associated with higher Ki67 (p = 0.0081, p &lt; 0.0001) but not RS. Among the 49% of patients with intermediate Ki67 of 6-29%, the distribution of low, intermediate, and high RS was 24%, 65%, and 11%, respectively. Conclusions: In this group of patients selected to have a 21-gene RS, there was no correlation between Ki67 and RS in the overall population, and fair agreement between high Ki67 and high RS. Among the approximately one-half with an intermediate Ki67 of 6-29%, 89% would be spared chemotherapy based on a low-intermediate RS. In patients with high Ki67, 68% might be spared chemotherapy based on the RS. In the low Ki67 group, 6% had a high RS. Ki67 has limited utility in identifying patients with high or low RS.

RASSF4 inhibits cell proliferation and increases drug sensitivity in colorectal cancer through YAP/Bcl-2 pathway.

The RASSF family proteins have been implicated in the development of human cancers. To date, the expression pattern and biological significance of RASSF4 in colorectal cancers (CRC) have not been fully investigated. In the current study, we explored expression pattern of RASSF4 in 118 CRC specimens and 30 adjacent ‘normal’ colon tissues by immunohistochemistry. The results showed that RASSF4 was downregulated in CRC tissues compared with adjacent ‘normal’ tissues. RASSF4 downregulation significantly associated with advanced tumour‐node‐metastasis (TNM) stage, T status, positive node status and high Ki‐67 index. Analysis of TCGA dataset also supported RASSF4 downregulation in CRC tissues. Ectopically expressed RASSF4 in LoVo cells inhibited cell growth, colony formation, cell cycle progression and increased the sensitivity to 5‐FU treatment. Annexin V/PI apoptosis assay showed that RASSF4 overexpression increased 5‐FU‐induced apoptosis and downregulated the mitochondrial membrane potential. In addition, Western blot demonstrated that RASSF4 overexpression repressed YAP and Bcl‐2 while upregulating p21 expression. YAP knockdown abolished the role of RASSF4 on Bcl‐2. ChIP assay showed that TEAD4, a major YAP binding transcription factor, could bind to the promoter regions of Bcl‐2. In conclusion, our data showed that RASSF4 was downregulated in human CRC. RASSF4 regulated malignant behaviour through YAP/Bcl‐2 signalling in CRC cells.

Survival characteristics of fibrolamellar hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results database study.

BACKGROUNDFibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinct type of hepatocellular carcinoma that frequently presents in an advanced stage in younger patients with no underlying liver disease. Currently, there is a limited understanding of factors that impact outcomes in FL-HCC.AIMTo characterize the survival of FL-HCC by age, race, and surgical intervention.METHODSThis is a retrospective study of The Surveillance, Epidemiology, and End Results database. We identified patients with FL-HCC between 2000-2018 by using an ICD-O-3 site code C22.0 and a histology code 8171/3: Hepatocellular carcinoma, fibrolamellar. In addition, demographics, tumor characteristics, types of surgical procedure, stages, and survival data were obtained. We conducted three separate survival analyses by age groups; ≤ 19, 20-59, and ≥ 60-year-old, and race; White, Black, Hispanic, Asian and Pacific islanders (API), and surgical types; Wedge resection or segmental resection, lobectomy, extended lobectomy (lobectomy + locoregional therapy or resection of the other lobe), and transplant. The Chi-Square test analyzed categorical variables, and continuous variables were examined using the Mann-Whitney U test. The Kaplan-Meier survival curve was used to compare survival. Multivariate analysis was done with Cox regression analysis.RESULTSWe identified 225 FL-HCC patients with a mean age of 36.9. Overall median survival was 34 (95%CI: 27-41) mo. Patients ≤ 19-years-old had more advanced disease with positive lymph nodes status. However, they received more surgical interventions such as a wedge, segmental resection, lobectomy, extended lobectomy, and transplant. Survival for ≤ 19 was 85 (95%CI: 37-137) mo, age 20-59 was 29 (95%CI: 18-41) mo, and age ≥ 60 years was 12 (95%CI: 7-31) mo (P < 0.001). There were no differences in stage, lymph node status, metastasis status, and surgical treatment among races. The median survival were; Whites had 39 (95%CI: 29-63), Blacks 26 (95%CI: 5-92), Hispanics 31 (95%CI: 11-54), and APIs 28 (95%CI: 5-39) mo (P = 0.28). Of 225 patients, 111 FL-HCC patients had surgical procedures. Median survivals for a wedge or segmental resection was 112 (95%CI: 78-NA), lobectomy was 92 (95%CI: 57-NA), extended lobectomy was 54 (95%CI: 23-NA), and a transplant was 63 (95%CI: 20-NA) mo (P < 0.001). The median survival was better in patients who had surgical treatments regardless of lymph nodes or metastasis status (P < 0.001).CONCLUSIONFL-HCC occurs in a primarily younger population, but survival can be prolonged despite the aggressive disease. There were no racial differences in the survival of FL-HCC; however, Asians with FL-HCC tended to be older than in other races. Surgical treatment provided better survival even in those patients with nodal disease or metastases. Although future studies are needed to explore other therapies for FL-HCC, surgical options should be considered in all cases of FL-HCC unless contraindicated.

HE4 is associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients.

To explore whether HE4 was associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients. Ninety-six primary fallopian tube carcinoma (PFTC) patients from March 2011 to June 2019 were enrolled in this study. Serum CA125 and HE4 concentrations were measured at four time points including primary diagnosis, postsurgery, pre-recurrence, and recurrence. The relations between clinical risk prognostic factors with HE4 concentrations were investigated, and multivariate survival analysis was used to calculate the hazard ratios between HE4 levels with recurrence-free survival and overall survival. HE4 were significantly elevated in poor performance status, advanced stage, high histological grade and residual tumor diameter >1 cm, and positive lymph node status, respectively, compared with those in well performance status, early stage, low histological grade, residual tumor diameter ≤1 cm, and negative lymph node status, respectively. Multivariate survival analysis indicated serum HE4 can predict outcome of recurrence-free survival and overall survival with hazard ratios of 9.92 (95% confidence interval [CI]: 2.95-33.32) and 3.12 (95% CI: 1.07-9.08), respectively. HE4 is associated with clinical risk prognostic factors in PFTC and contributes to predict survival outcome in PFTC cases.

LONG-TERM RADICAL PROSTATECTOMY ONCOLOGIC OUTCOMES IN PATIENTS WITH CLINICALLY LOCALLY ADVANCED PROSTATE CANCER: A SINGLE-CENTER STUDY.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in males worldwide and placed fifth in cancer mortality among males. Between 14-24% of PCa patients have newly diagnosed advanced stages, which paradoxically has remained stable over time. To estimate and compare long-term radical prostatectomy (RP) oncologic outcomes in patients with clinically locally advanced prostate cancer (LAPCa), to determine the prognostic significance of common clinical-pathological parameters. The study included 105patients with LAPCa who underwent RP with extended pelvic lymphadenectomy between September 2003- April 2015. Kaplan - Meier method was used for calculating biochemical recurrence- (BRFS), progression-free- (PFS), overall (OS), and prostate cancer-specific survival (PCSS) rates. Analyses of features associated with outcomes were conducted using Cox proportional hazards regression model. Patients from cT3b group had worse PFS, OS and PCSS rates in comparison with cT3a, while there was no significant difference in BRFS rates. Preoperative serum prostate-specific antigen level (hazard ratio (HR) 1.023, 95% confidence interval (CI): 1.014-1.033, p < 0.001), pT3a (HR 3,027, 95% CI: 1.449-7.096, p < 0.01), pT3b (HR 2.792, 95% CI: 1.133-6.881, p < 0.05) pT4stage (HR 31.12, 95% CI: 7.646-126.6p< 0.001) and positive lymph nodes status (HR 6.503, 95% CI: 3.190-13.25, p < 0.001) were significant factors in BRFS. Preoperative serum prostate-specific antigen level (HR 1.018, 95% CI: 1.007-1.030, p = 0.001) and positive lymph nodes status (HR 3.191, 95% CI: 1.672-6.088, p < 0.001) were significant factors in PFS and PCSS. RP as the initial treatment option of multimodal therapy in the management of LAPCa patients demonstrates encouraging oncologic outcomes. Patients from the cT3b group had the worse rates of PFS, OS, and PCSS in comparison with the cT3a group. Heterogeneity of LAPCa patients' outcomes reflects the insufficiency of the existing clinical risk classification for the prediction of systemic progression and cancer-specific survival.

MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting.

The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology. Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting.

Factors Associated with Patient Survival in Clear Cell Adenocarcinoma of the Cervix: A Single-Center Experience in China.

PurposeClear cell adenocarcinoma of the cervix (CCAC) is a rare pathological type of cervical cancer. This study aimed to report our clinical experience with CCAC treatment and analyze the factors associated with patient survival.Patients and MethodsThis single-center study included patients diagnosed with CCAC and treated between 01/2003 and 12/2017 at the Obstetrics and Gynecology Hospital of Fudan University. The patients diagnosed with CCAC that underwent radical resection were included. The Kaplan–Meier method and multivariable Cox regression analysis were performed to determine factors associated with patient survival.ResultsFifty-four patients were included. None were exposed to diethylstilbestrol. The median follow-up was 96 (13.0, 120.0) months. The median recurrence-free survival (RFS) and overall survival (OS) were 68 and 78 months, respectively. Positive pelvic lymph nodes (HR=2.87, 95% confidence interval [CI] 1.14–7.22, P=0.03), tumor size >4 cm (HR=3.31, 95% CI 1.35–8.12, P=0.01), International Federation of Gynecology and Obstetrics (FIGO) IB2-IIA2 stage (HR=2.49, 95% CI 1.56–3.99, P=0.02), and postoperative therapy (HR=1.73, 95% CI 1.07–2.81, P=0.03) were associated with OS. Multivariable analysis showed that FIGO stage IB2-IIA2 (HR=2.36, 95% CI 1.52–3.68, P<0.01) and lymph node status (HR=3.05, 95% CI 1.12–8.28, P=0.03) were independently associated with OS.ConclusionAdvanced FIGO stage and positive lymph node status are independently associated with shorter survival in patients with CCAC who were not exposed to diethylstilbestrol. After surgery, chemotherapy and concurrent chemoradiotherapy were not independently associated with the prognosis of patients with CCAC.

Incorporation of immunohistochemistry in the assessment of survival and prognosis of endometrial cancers: Are we ready for the change?

Objectives: The aim of the study was to determine the mismatch repair (MMR) proteins and p53 expression by immunohistochemistry in operable endometrial carcinoma (EC) patients. The study aimed to analyze and correlate clinicopathological factors and survival with MMR and p53 immunohistochemistry markers. Material and Methods: A retrospective cohort study of 115 cases of carcinoma endometrium who underwent primary surgery in our hospital from July 1, 2013, to December 31, 2020, with a minimum follow-up of 1 year. Available tissue blocks were stained for IHC expression of MMR and p53 proteins. Patients were stratified into Type I and Type II on basis of histopathology. Clinicopathological factors, overall survival (OS), and disease-free survival (DFS) were then compared on the basis of MMR deficiency and p53 status. Results: The mean age of study population was 58.9 years with a mean body mass index of 31.61 kg/m2. The mean follow-up was 41.29 months. Ninety-seven patients underwent IHC staining for MMR and p53 proteins. Among these 97 patients, 79 patients belonged to Type I histopathology and 18 patients belonged to Type II histopathology. The 79 patients of Type I histopathology were further divided into MSS or microsatellite stable group and MSI or microsatellite instable group. MMR deficit status was seen in 17 (21.5%) patients and 62 (78.5%) patients were MSS. For the 18 cases of Type II ECs, 5 (27.8%) patients were p53 positive whereas 13 (72.2%) patients were p53 negative. For patients with Type I histopathology; the clinicopathological factors such as stage, age, grade of the tumor, lymph-vascular space involvement, lymph node status, and myometrial invasion were compared between the MSI and MSS groups. Patients with microsatellite instability were more likely to present with a higher grade, a positive lymph node status, and with lymph-vascular space invasion. The OS and DFS are not significantly affected in patients with loss of MMR proteins. Due to a smaller number of cases in p53 group, clinicopathological features and survival could not be compared. Conclusion: Analyzing of immunohistochemistry status for evaluating the microsatellite instability in patients with Type I endometrioid adenocarcinomas is an alternative and efficient tool in predicting the prognosis for these patients. Further studies with more sample size can help us in studying the impact of MSI and p53 on OS and DFS and for guiding in the management of the same.

Prognostic Effect of Primary Recurrence Patterns in Squamous Cervical Carcinoma After Radical Surgery

ObjectiveTo examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment.MethodsPrimary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram.ResultsA total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075–0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151–3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317–0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838–7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325–2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS.ConclusionsPrimary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype.

Early-onset non-metastatic colon cancers do not portend worse prognosis - implications for adjuvant chemotherapy.

Early-onset colon cancers are increasing and the independent influence of age on prognosis and therapeutic efficacy of adjuvant therapy is unclear. The primary aim of the present study was to determine if young age was an independent prognostic factor for survival. Secondarily, age would be used in the context of known factors that predict benefit with adjuvant chemotherapy in stages II and III. Retrospective, single centre study of operated, non-metastatic colon cancer (> 15cm from anal verge) without pre-operative therapy. Early onset cancers were defined as age ≤ 45years. Primary endpoint was disease-free survival (DFS). Six-hundred thirty-three patients were included with 206 (32.5%) early-onset cancers. With a median follow-up of 48months, 5-year DFS was 79.5% and 76.2% for early and late-onset cancers, respectively (p - 0.585). In multivariate analysis, only tumour sidedness, family history, T4 stage, node positivity and microsatellite instability status influenced DFS and not the age of onset (HR - 0.969; 95% - 0.63-1.49). These results were consistent with different models and with stage-wise distribution. Early-onset colon cancers treated with curative intent had survivals similar to older cohorts. Age was not an independent prognostic factor for recurrences. Age did not influence disease-free survival when stage-wise predictive variables for therapeutic benefit with adjuvant chemotherapy were considered.

Non-phosphorylated Tyr-1248 form of human epidermal growth factor receptor 2 (HER2) predicts resistance to trastuzumab therapy and poor disease-free survival of HER2-positive breast cancer patients

AimTo determine the predictive value of phosphorylated human epidermal growth factor receptor 2 (pHER2Y1248) status in breast cancer (BC) patients undergoing trastuzumab-based adjuvant therapy.MethodsImmunohistochemical status of pHER2Y1248, EGFR/HER1, HER3, and HER4 was determined in 124 consecutive HER2-positive BC patients (median age [range] = 57 years [49.0-64.0]) treated at the University Hospital for Tumors, Zagreb, between 2008 and 2011. The median follow-up was 84 months (60.0-84.0). Prognostic factors of disease free survival (DFS) rate were evaluated with Kaplan-Meier/log-rank test and Cox regression analysis.ResultspHER2Y1248, HER1, HER3, and HER4 were expressed in 66.1%, 9.7%, 70.2%, and 71.0% of patients, respectively. Disease progression (DP) was observed in 17.1% of pHER2Y1248-positive and 47.6% of pHER2Y1248-negative BCs (P = 0.001). Kaplan-Meier analysis showed a worse five-year DFS in pHER2Y1248-negative patients who were older than 60 years (P < 0.001) and had positive lymph node status (P < 0.001); tumor size >2.0 cm (P < 0.001); higher histological grade (P < 0.001); HER2E intrinsic subtype (P < 0.001), negative hormone receptors (P < 0.001); negative HER1 status (P < 0.001), positive HER3 (P = 0.002); and/or positive HER4 (P = 0.002) status. The only negative prognostic factor for five-year DFS in multivariate Cox regression analysis was pHER2Y1248-negative (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.8-7.2, P < 0.001) and lymph node-positive status (HR 3.6, 95% CI 1.3-9.8, P = 0.014).ConclusionpHER2Y1248 predicts sensitivity to trastuzumab and a better five-year DFS regardless of any other prognostic parameter. In HER2-positive BC patients. Non-phosphorylated HER2Y1248 is a strong predictor of trastuzumab resistance and a poor DFS.

Impact of Postoperative Chemotherapy in Patients with Gastric/Gastroesophageal Adenocarcinoma Treated with Perioperative Chemotherapy.

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0–62.4 vs. 19.0 months; 95%CI 10.5–27.5; p = 0.008 and median OS 35.7 months; 95%CI 0–73.6 vs. 19.2 months; 95%CI 7.8–30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients.