Optimization of Extended Pelvic Lymph Node Dissection Side for Prostate Cancer.

BACKGROUND: This study aimed to show the association between tumor location and laterality of positive lymph nodes by evaluating biopsy and magnetic resonance imaging (MRI) findings, and to optimize the extended pelvic lymph node dissection (ePLND) side for prostate cancer. METHODS: The study enrolled patients who underwent robot-assisted radical prostatectomy with ePLND. Tumor locations were determined according to International Society of Urological Pathology grade group 4/5 in biopsies and Prostate Imaging-Reporting and Data System category 4/5 in MRI results. The concordance of tumor location lobe and positive lymph node side with the performance of tumor location-guided ePLND for positive lymph node detection was evaluated. RESULTS: For 301 patients who underwent ePLND at Kyushu University Hospital, tumor locations determined by biopsy and MRI findings showed no lesion in 8 (2.7%) patients, unilateral lobe in 223 (74.1%) patients, and bilateral lobe in 70 (23.3%) patients. The accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were 99.6% and 97.3%, respectively. Among the patients at St. Luke's International Hospital, the accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were estimated to be 99.0% and 97.3%, respectively. CONCLUSIONS: This study proposed tumor location-guided ePLND according to biopsy and MRI findings. This novel strategy is expected to reduce the burden of bilateral ePLND at the cost of acceptable risk of failing to detect positive lymph nodes.

Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

The Key Role of Tumor Budding in Predicting the Status of Lymph Node Involvement in Early Gastric Cancer Patients: A Clinical Multicenter Validation in China.

BACKGROUND: Accurate preoperative prediction of lymph node (LN) involvement is essential for the management of early gastric cancer (EGC). Our objective was to formulate a potent nomogram for predicting LN involvement in EGC by leveraging an innovative predictor of tumor budding. METHODS: We assembled a cohort of EGC patients who underwent radical surgery at two tertiary cancer centers. Tumor budding was stratified by using an optimal cutoff value and integrated with other clinicopathological variables to ascertain the risk factors associated with LN involvement. A nomogram was developed and its predictive performance was assessed by using receiver operating characteristic (ROC) curves and calibration plots. In addition, we conducted decision curve analysis to evaluate its clinical utility. Finally, an external validation was conducted by using an independent cohort. RESULTS: Finally, 307 eligible patients (215 in the primary cohort and 92 in the validation cohort) were included. Tumor budding, categorized by a count of two, exhibited a robust association with LN involvement (OR 14.12, p = 0.012). Other significant risk factors include lymphovascular invasion, depth of tumor invasion, ulceration, and tumor differentiation. Notably, the nomogram demonstrated exceptional discriminative power (area under the ROC curve, 0.872 in the primary cohort and 0.885 in the validation cohort) and precise predictive capabilities. Furthermore, the nomogram showed notable clinical applicability through decision curve analysis, particularly in endoscopic curability C-2, by mitigating the risk of overtreatment. CONCLUSIONS: Tumor budding is a robust predictor of LN involvement in EGC. The incorporation of tumor budding into a nomogram is an effective strategy, thereby informing and enhancing clinical decision-making.

Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is recommended when lymph node metastasis is evident or strongly suspected on preoperative imaging studies, even for a completely resectable (cT1-2) tumor with minimal lymph node involvement (cN1). We evaluated the validity of upfront surgical approach in this patient group. METHODS: We retrospectively reviewed data from 247 patients with cT1-2 esophageal squamous cell carcinoma (ESCC) who underwent upfront radical esophagectomy followed by the pathology-based adjuvant treatment. Oncologic outcomes of cN1 patients were compared with those of cN0 patients. RESULTS: There were 203 cN0 and 44 cN1 patients. The lymph node yield was 62.0 (interquartile range [IQR], 51.0-76.0) in cN0 and 65.5 (IQR, 57.5-85.0) in cN1 patients (p = 0.033). The size of metastatic node was 0.6 cm (IQR, 0.4-0.9 cm) in cN0 and 0.8 cm (IQR, 0.5-1.3 cm) in cN1 patients (p = 0.001). Nodal upstaging was identified in 29.1% of cN0 and 40.9% of cN1 patients, whereas 18.2% of the cN1 had no actual lymph node metastasis (pN0). The 5-year disease-free survival rate was not significantly different between the groups (cN0, 74.4%; cN1, 71.8%; p = 0.529). Survival rates were closely correlated with pN stage, and a multivariate analysis revealed that pN2-3 stage was a risk factor for poor disease-free survival. CONCLUSIONS: Upfront radical surgery provided accurate nodal staging information, potentially sparing some cN1 patients from unnecessary nCRT while demonstrating comparable survival rates. It might be a valid option for the treatment of cT1-2N1 ESCC.

Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.

BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

C/EBP-Family Redundancy Determines Patient Survival and Lymph Node Involvement in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a poor clinical prognosis and unsatisfactory treatment options. We previously found that the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBPδ) is lowly expressed in PDAC compared to healthy pancreas duct cells, and that patient survival and lymph node involvement in PDAC is correlated with the expression of C/EBPδ in primary tumor cells. C/EBPδ shares a homologous DNA-binding sequence with other C/EBP-proteins, leading to the presumption that other C/EBP-family members might act redundantly and compensate for the loss of C/EBPδ. This implies that patient stratification could be improved when expression levels of multiple C/EBP-family members are considered simultaneously. In this study, we assessed whether the quantification of C/EBPß or C/EBPγ in addition to that of C/EBPδ might improve the prediction of patient survival and lymph node involvement using a cohort of 68 resectable PDAC patients. Using Kaplan-Meier analyses of patient groups with different C/EBP-expression levels, we found that both C/EBPß and C/EBPγ can partially compensate for low C/EBPδ and improve patient survival. Further, we uncovered C/EBPß as a novel predictor of a decreased likelihood of lymph node involvement in PDAC, and found that C/EBPß and C/EBPδ can compensate for the lack of each other in order to reduce the risk of lymph node involvement. C/EBPγ, on the other hand, appears to promote lymph node involvement in the absence of C/EBPδ. Altogether, our results show that the redundancy of C/EBP-family members might have a profound influence on clinical prognoses and that the expression of both C/EPBß and C/EBPγ should be taken into account when dichotomizing patients according to C/EBPδ expression.

Is complete mesocolic excision or total mesorectal excision necessary during cytoreductive surgery in ovarian peritoneal carcinomatosis with colonic involvement?

INTRODUCTION: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy are effective in the treatment of ovarian peritoneal carcinomatosis (OPC). Colon resection is often required to achieve maximal cytoreduction during CRS. The success of complete mesocolic excision (CME) and total mesorectal excision (TME) in the surgical treatment of primary colorectal tumors is well-known. Our study aimed to investigate the factors affecting mesocolic lymph node metastasis (MLNM) and the contribution of CME/TME techniques to maximal cytoreduction in patients diagnosed with ovarian peritoneal carcinomatosis (OPC) with colon metastasis. PATIENTS AND METHODS: Between 2004-2020, 30 patients who underwent colorectal resection with CME/TME techniques due to OPC-related colon metastasis were retrospectively analyzed. RESULTS: The median age of patients was 61 (33-86). Six (20%) patients underwent total colectomy, 7 (23%) subtotal colectomy, 6 (20%) right hemicolectomy, 4 (13%) left hemicolectomy, and 7 (23%) rectosigmoid resection. Histopathological diagnosis was high-grade serous carcinoma in 29 (97%) patients, and malignant mixed Mullerian tumor in 1 (3%) patient. MLNM was detected in 17 (56%) of 30 patients. There was a significant relationship between MLNM and pelvic and para-aortic lymph node metastasis (PALNM) (p = 0.009) and lymphovascular invasion in primary ovarian tumors (p = 0.017). There was no significant relationship between MLNM and depth of colonic invasion (p = 0.463), histological grade (p = 0.711), and primary/secondary surgery (p = 0.638). MLNM was seen in 8 (47%) of 17 patients with only serosal invasion. CONCLUSION: A high rate of MLNM can be seen in OPC-induced colon metastasis regardless of the degree of colon wall invasion. In patients with PALNM, the frequency of MLNM increases. We believe that if colon resection is to be performed in OPC, a colectomy should be performed by CME/TME principles to achieve maximal cytoreduction.

Factors affecting recurrence and metastasis in conjunctival melanoma.

PURPOSE: To evaluate clinical and demographic characteristics and factors affecting recurrence, metastasis, and survival in conjunctival melanoma (CM). METHODS: The clinical records of 45 patients who were treated for CM between October 1998 and June 2022 were retrospectively evaluated. Age, gender, presence of underlying conjunctival nevus-primary acquired melanosis (PAM), tumor stage according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, tumor basal diameter, tumor thickness, lymph node (LN) involvement, metastasis, presence of tumor at the surgical margin, treatment method, need for adjuvant therapy, local tumor control, recurrence, and survival were recorded. RESULTS: Twenty-one (46.7%) patients were female and 24 (53.3%) patients were male. The mean age at diagnosis was 53.2 ± 16.1 years. Median follow up time was 12 (1-300) months. Fifteen (33.3%) patients had conjunctival PAM; 2 (4.4%) patients had conjunctival nevus. The tumor stage was T1 in 24 (55.8%), T2 in 13 (30.2%), and T3 in 6 (14.0%) of the cases. The T stage in 2 cases could not be determined. For stage T1 and T2 CM, in addition to excisional biopsy (EB) and cryotherapy, alcohol epitheliectomy (AE) was performed in 17 cases (37.8%), superficial sclerectomy (SS) was performed in 7 (15.6%), and amnion membrane transplantation (AMT) due to a large conjunctival defect in 9 (20.0%). Six (14.0%) T3 cases underwent primary exenteration. Positive surgical margins were observed in 23 (51.1%) of the excised tumors at histopathologic examination. Adjuvant topical mitomycin-C (MMC) was used in 7 (30.4%) and strontium-90 episcleral brachytherapy in 4 (17.4%) of the 23 cases with tumor-positive borders. During the follow-up, recurrence was seen in 14 (31.1%) cases. According to Kaplan Meier analysis, the mean time to recurrence development was 90.5 ± 16.1 months and the 5-year recurrence free rate was 52.0%. Fourteen of the recurrent cases underwent EB + cryotherapy, 3 underwent AE + SS, and 3 underwent secondary exenteration. Metastasis and LN involvement occurred in 11 (24.4%) and 8 (17.8%) of the cases, respectively. Four (8.9%) cases expired during follow-up. According to Kaplan-Meier analysis, the mean time to metastasis was 106.2 ± 17.3 months and the 5-year metastasis free rate was 52.0%. While recurrence was more frequent in CM developing from PAM/nevus, metastasis was more frequent in men and those with LN involvement. CONCLUSION: Conjunctival melanoma was a malignant tumor with high recurrence and metastasis rates. Precursor nevus/PAM is a risk factor for recurrence, while male gender and regional LN involvement were risk factors for metastasis in this study.

Metastatic potential of T1a and T1b non-small cell lung cancer: analysis in the Czech population.

INTRODUCTION: Lung cancer is the most common cause of cancer death in the Czech Republic, in part due to its significant metastatic potential. The aim of this study was to collect real data on the metastatic potential and clinical characteristics of T1a and T1b lung cancer in the Czech population and to investigate potential factors that would predict an increased risk of lymph node metastasis. METHODS: Prospective-retrospective study conducted at the Department of Surgery of the University Hospital Ostrava during the period from January 1, 2015, to July 31, 2022. The study included patients who underwent lobectomy or bilobectomy for T1a and T1b non-small cell lung carcinoma. RESULTS: Out of a total of 165 patients with T1a and T1b lung carcinoma, 17.6% of patients were confirmed to have metastatic involvement of the lymph nodes (with 9.1% classified as N2 lymph node involvement). The highest percentage of positive lymph nodes was observed in patients with tumors located in the upper left lobe (29.5%) and lower right lobe (23.3%). Adenocarcinoma was the most commonly metastasizing carcinoma, with 21.1% of patients showing positive lymph nodes. Neuroendocrine carcinoma metastasized in 19.4% of cases, while squamous cell carcinoma did so in 6.8% of cases. The cumulative risk of having positive lymph nodes in T1a and T1b adenocarcinoma located in the upper left lobe reached 40.0%, of which the risk of N2 lymph node involvement was 25.0%. CONCLUSION: T1a/b non-small cell lung cancer exhibits significantly lower metastatic potential than T1c tumors and higher. Adenocarcinoma showed a 3-fold higher metastatic potential than squamous cell carcinoma, indicating the need for increased attention in the treatment of lung adenocarcinoma, especially in tumors localized in the upper left lobe, where a cumulative risk of lymph node metastasis of up to 40% was observed.

Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.

Characterization of Extracapsular Lymph Node Involvement and Its Clinicopathological Characteristics in Stage II-IIIA Lung Adenocarcinoma.

BACKGROUND: The prognostic impact and clinicopathological characteristics of extracapsular lymph node involvement (ECLNI) in patients with surgically resected lung adenocarcinoma (LUAD) remain unknown in the context of the eighth edition N classification. PATIENTS AND METHODS: We retrospectively reviewed 279 patients with stage II-IIIA LUAD who underwent lobectomy and lymphadenectomy. The correlations of ECLNI presence and clinicopathological profiles were analyzed. We also assessed the impact of ECLNI on the postoperative survival of pN1 and pN2 LUAD patients. RESULTS: ECLNI-positive status was more common in patients with high lymph node yield and in patients with multiple stations involved. The logistic regression model identified tumor spread through air spaces, micropapillary component, cribriform component, and nodal stage as predictive factors for ECLNI presence. LUAD patients with ECLNI presence had an increased risk of locoregional recurrence compared with those without (p < 0.001). Presence of ECLNI was confirmed as an independent risk factor for worse recurrence-free survival (RFS) (p < 0.001) and overall survival (OS) (p < 0.001) in the entire cohort. Among the 61 patients with ECLNI(+)pN2 disease, our analysis revealed that adjuvant radiation was a significant predictor of improved RFS and OS. In addition, ECLNI status provides additional precision in stratifying pN1 and pN2 patients with significantly different RFS and OS. CONCLUSIONS: Our data suggest that ECLNI remains a strong prognosticator of unfavorable OS and RFS for LUADs in the context of the eighth edition N classification. Adjuvant radiation should be actively considered for pN1b and pN2 LUAD patients with ECLNI presence.

HPV E6/E7 mRNA in situ hybridization in endocervical adenocarcinoma: implications for prognosis and diagnosis.

BACKGROUND: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it. METHODS: We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). RESULTS: The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p = 0.002) and treatment (C-index = 0.578, p < 0.001). CONCLUSIONS:  HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

External validation of the Memorial Sloan Kettering Cancer Centre and Briganti nomograms for the prediction of lymph node involvement of prostate cancer using clinical stage assessed by magnetic resonance imaging.

OBJECTIVES: To evaluate the impact of using clinical stage assessed by multiparametric magnetic resonance imaging (mpMRI) on the performance of two established nomograms for the prediction of pelvic lymph node involvement (LNI) in patients with prostate cancer. PATIENTS AND METHODS: Patients undergoing robot-assisted extended pelvic lymph node dissection (ePLND) from 2015 to 2019 at three teaching hospitals were retrospectively evaluated. Risk of LNI was calculated four times for each patient, using clinical tumour stage (T-stage) assessed by digital rectal examination (DRE) and by mpMRI, in the Memorial Sloan Kettering Cancer Centre (MSKCC; 2018) and Briganti (2012) nomograms. Discrimination (area under the curve [AUC]), calibration, and the net benefit of these four strategies were assessed and compared. RESULTS: A total of 1062 patients were included, of whom 301 (28%) had histologically proven LNI. Using DRE T-stage resulted in AUCs of 0.71 (95% confidence interval [CI] 0.70-0.72) for the MSKCC and 0.73 (95% CI 0.72-0.74) for the Briganti nomogram. Using mpMRI T-stage, the AUCs were 0.72 (95% CI 0.71-0.73) for the MSKCC and 0.75 (95% CI 0.74-0.76) for the Briganti nomogram. mpMRI T-stage resulted in equivalent calibration compared with DRE T-stage. Combined use of mpMRI T-stage and the Briganti 2012 nomogram was shown to be superior in terms of AUC, calibration, and net benefit. Use of mpMRI T-stage led to increased sensitivity for the detection of LNI for all risk thresholds in both models, countered by a decreased specificity, compared with DRE T-stage. CONCLUSION: T-stage as assessed by mpMRI is an appropriate alternative for T-stage assessed by DRE to determine nomogram-based risk of LNI in patients with prostate cancer, and was associated with improved model performance of both the MSKCC 2018 and Briganti 2012 nomograms.

Tumor diameter as a predictor of lymph node involvement in endometrioid type endometrial adenocarcinomas.

AIM: To analyze the risk factors of lymph node involvement in pure endometrioid type endometrial cancer and assess factors that necessitate lymphadenectomy. METHODS: Patients who had been operated on due to endometrial cancer and whose final pathology was reported as pure endometrioid carcinoma between January 2014 and January 2020 were assessed. Hysterectomy, bilateral salpingo-oophorectomy, and systematic lymphadenectomy were performed in all patients. All specimens were reported by expert gynecopathologists. RESULTS: The lymph node positivity rate was 14.4%. When the study population was classified according to the Mayo risk criteria; lymph node involvement in the low-risk and high-risk groups was 9.1% and 14.8%, respectively and there was no statistically difference (p > 0.05). The median of tumor size and the rate of deep myometrial invasion, lymphovascular space invasion, adnexal involvement, FIGO grade 3 tumor were found significantly higher in the positive lymph node group in univariate analysis. In the receiver operating characteristic curve analysis, the cut-off value of the tumor diameter was determined as 47.5 mm (sensitivity 85%, specificity 62%). Every 10 mm increase in tumor diameter increased the risk of lymph node involvement 10 times. CONCLUSION: This study defined that the tumor diameter is an independent predictor for lymphatic dissemination. In the future, it could be shown that even with new modeling based on tumor diameter, lymphadenectomy or adjuvant radiotherapy requirements would be reevaluated.

Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤2 cm in size: A retrospective cohort study.

BACKGROUND/PURPOSE: Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2 cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results. METHODS: We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2 cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS). RESULTS: Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p < 0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p = 0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p = 0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma. CONCLUSION: For lung cancer patients with primary tumor ≤2 cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS.

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. METHODS: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. RESULTS: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. CONCLUSIONS: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.

Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer.

OBJECTIVE: This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. METHODS: We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. RESULTS: After median follow-up of 58.3 months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P = 0.700 and P = 0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P < 0.001 and P < 0.001). CONCLUSIONS: This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

A novel prediction method for lymph node involvement in endometrial cancer: machine learning.

OBJECTIVE: The necessity of lymphadenectomy and the prediction of lymph node involvement (LNI) in endometrial cancer (EC) have been hotly-debated questions in recent years. Machine learning is a broad field that can produce results and estimations. In this study we constructed prediction models for EC patients using the Naïve Bayes machine learning algorithm for LNI prediction. METHODS: The study assessed 762 patients with EC. Algorithm models were based on the following histopathological factors: V1: final histology; V2: presence of lymphovascular space invasion (LVSI); V3: grade; V4: tumor diameter; V5: depth of myometrial invasion (MI); V6: cervical glandular stromal invasion (CGSI); V7: tubal or ovarian involvement; and V8: pelvic LNI. Logistic regression analysis was also used to evaluate the independent factors affecting LNI. RESULTS: The mean age of patients was 59.1 years. LNI was detected in 102 (13.4%) patients. Para-aortic LNI (PaLNI) was detected in 54 (7.1%) patients, of which four patients had isolated PaLNI. The accuracy rate of the algorithm models was found to be between 84.2% and 88.9% and 85.0% and 97.6% for LNI and PaLNI, respectively. In multivariate analysis, the histologic type, LVSI, depth of MI, and CGSI were independently and significantly associated with LNI (p<0.001 for all). CONCLUSIONS: Machine learning may have a place in the decision tree for the management of EC. This is a preliminary report about the use of a new statistical technique. Larger studies with the addition of sentinel lymph node status, laboratory findings, or imaging results with machine learning algorithms may herald a new era in the management of EC.

Single-Center Study of Lymphoepithelioma-Like Carcinoma of Uterine Cervix over a 10-Year Period.

Background and objectives: Lymphoepithelioma-like carcinoma (LELC) is a histological type of malignant tumor arising from the uncontrolled mitosis of transformed cells originating in epithelial tissue. It is a rare subtype of squamous cell carcinoma of the uterine cervix. There are significant differences in frequency, mean age, viral status, and outcomes in Asian or Caucasian patients. Materials and Methods: A retrospective study of all cases of lymphoepithelioma-like carcinoma of the cervix at the Clinic of Oncogynecology, University Hospital, Pleven, Bulgaria between 1 January 2007 and 31 December 2016 was performed. All patients were followed-up till March 2019. We analyzed some clinical characteristics of the patients, calculated the frequency of lymphoepithelioma-like carcinoma of the cervix from all patients with stage I cervical cancer, and looked at the overall survival rate, the 5-year survival rate, and the correlation between overall survival, lymph node status, and the size of the tumor. Results: The frequency of lymphoepithelioma-like carcinoma was 3.3% for all cases with cervical carcinoma at stage I. The mean age of the patients with LELC was 49.6 years (range 32-67). Fourteen patients (82.4%) were in the FIGO IB1 stage, three patients (17.6%) were in the FIGO IB2 stage. Lymph nodes were metastatic in three patients (17.6%), non-metastatic in 13 patients (76.5%), and unknown in one patient. The overall survival rate was 76.47% for the study period and the 5-year survival rate of the patients that were followed-up until the 5th year (14 patients) was 69.23%. Conclusions: Lymphoepithelioma-like carcinoma is a rare SCC subtype, but it could be more frequent among western patients than previously thought. Our results do not confirm the data showing low risk of lymph metastasis and good prognosis of LELC, which is why we think that the treatment in these cases has to be more aggressive than is reported in the literature.

Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study.

BACKGROUND: Early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or younger and is associated with worse outcomes than later onset breast cancer. This study explored novel serum proteins as surrogate markers of prognosis in patients with EOBC. METHODS: Serum samples from EOBC patients (stages 1-3) were analysed using agnostic high-precision quantitative proteomics. Patients received anthracycline-based chemotherapy. The discovery cohort (n = 399) either had more than 5-year disease-free survival (DFS) (good outcome group, n = 203) or DFS of less than 2 years (poor outcome group, n = 196). Expressed proteins were assessed for differential expression between the two groups. Bioinformatics pathway and network analysis in combination with literature research were used to determine clinically relevant proteins. ELISA analysis against an independent sample set from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort (n = 181) was used to validate expression levels of the selected target. Linear and generalized linear modelling was applied to determine the effect of target markers, body mass index (BMI), lymph node involvement (LN), oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 status on patients' outcome. RESULTS: A total of 5346 unique proteins were analysed (peptide FDR p ≤ 0.05). Of these, 812 were differentially expressed in the good vs poor outcome groups and showed significant enrichment for the insulin signalling (p = 0.01) and the glycolysis/gluconeogenesis (p = 0.01) pathways. These proteins further correlated with interaction networks involving glucose and fatty acid metabolism. A consistent nodal protein to these metabolic networks was resistin (upregulated in the good outcome group, p = 0.009). ELISA validation demonstrated resistin to be upregulated in the good outcome group (p = 0.04), irrespective of BMI and ER status. LN involvement was the only covariate with a significant association with resistin measurements (p = 0.004). An ancillary in-silico observation was the induction of the inflammatory response, leucocyte infiltration, lymphocyte migration and recruitment of phagocytes (p < 0.0001, z-score > 2). Survival analysis showed that resistin overexpression was associated with improved DFS. CONCLUSIONS: Higher circulating resistin correlated with node-negative patients and longer DFS independent of BMI and ER status in women with EOBC. Overexpression of serum resistin in EOBC may be a surrogate indicator of improved prognosis.