Rate Of Lymphovascular Invasion Research Articles

Variation in the detection of lymphovascular invasion in T1 colorectal cancer and its impact on treatment: A nationwide Dutch study.

Lymphovascular invasion (LVI) plays an important role in determining the risk of lymph node metastasis (LNM) in T1 colorectal cancer (CRC) patients and influencing treatment decisions and patient outcomes. This study evaluated how the detection of LVI varies between Dutch laboratories and investigated its impact on the treatment and oncological outcomes of T1 CRC patients. Pathology reports and clinical data of T1 CRC patients who underwent local resection between 2015 and 2019 were obtained from the Dutch nationwide pathology databank (Palga cohort, n=5513). Data on the standard of LVI diagnosis (H&E/Immunohistochemistry) were not available. We categorized laboratories as low, average, or high detectors and evaluated the impact of LVI detection practice on the surgical resection rate and the proportion of LNM-negative (LNM-) surgeries. In the second part of the study, we used the Dutch T1 CRC Working Group cohort (n=1268) to evaluate the impact of LVI detection practice on cancer recurrences during follow-up. Multivariable logistic regression analyses and Cox proportional hazard regression were used to study the association between LVI detection practice and the outcomes. In the PALGA cohort, the proportion of surgical resections after local resection of a T1 CRC was significantly higher among patients diagnosed by laboratories with a high LVI detection rate (high vs. low: adjusted OR [aOR] 1.87; 95% confidence interval [CI] 1.52-2.31) as was the proportion of LNM-surgeries (aOR 1.73; 95% CI 1.39-2.15). In the second cohort, no significant difference was observed in cancer recurrences among patients diagnosed in laboratories with high detection rates compared with low detection rates (aHR 2.23; 95% CI 0.94-5.23). These findings suggest that a high detection rate of LVI does not improve oncological outcomes and may expose more patients to unnecessary oncological surgery, emphasizing the need for standardization of LVI diagnosis.

PD-L1 and PD-L2 Expression in Different Tumor Stages and Types of Malignant Salivary Gland Neoplasms: A Single-center Experience.

There is a limited amount of data on the role of programmed cell death ligand (PD-L) -1 and PD-L2 in salivary gland carcinomas. We aimed to evaluate the prognostic value of PD-L1 and PD-L2 expressions, which are closely related to immune mechanisms, with respect to salivary gland tumor types and stages. Data from patients with salivary gland masses surgically removed between 2006 and 2021, diagnosed with a malignant salivary gland neoplasm, were retrospectively analyzed. Immunoreactivity for PD-L1 and PD-L2 was performed on resection materials. The mean age of 90 patients was 52.1±18.8 and 46.7% were male. Overall, 55.6% of patients were diagnosed with adenoid cystic carcinoma (ACC), 23.3% with mucoepidermoid carcinoma (MEC), 16.7% with acinic cell carcinoma (AciCC), 3.3% with ductal carcinoma (DC), and 1 patient with pleomorphic adenoma ex carcinoma (PA-ex-CA). In all, 52% of ACC, 12% of AciCC, 24% of MEC, and 12% of DC cases were at stage IV. The tumor diameter, frequencies of lymphovascular invasion, metastasis, positive surgical margin, recurrence, and mortality rates of patients at stages III and IV were significantly larger than those at stages I and II ( P <0.05). The percentages of tumor cell score (TCS) and immune cell score (ICS) for PD-L1 were significantly higher among patients with MEC compared with those with other types of tumors ( P =0.0011). However, the percentages of combined score (CS) for PD-L1 and tumor cell score for PD-L2 were comparable among tumor types ( P >0.05). No significant difference was found in these scores for PD-L1 between tumor stages ( P >0.05), but for PD-L2, all patients at stage I had TCS <1% for PD-L2, while all patients at stages II and III, and 92% of patients at stage IV had TCS ≥1% ( P <0.0001). High expression of PD-L1 was mostly observed in MEC cases ( P =0.0016), while all patients with AciCC had a low PD-L1 expression level ( P =0.0206). The mean tumor diameter, rate of lymphovascular invasion, perineural invasion, metastasis, positive surgical margin, recurrence, type of treatment, mortality, and TILs ratio did not differ significantly according to PD-L1 expression level ( P >0.05). The percentage of tumor-infiltrating lymphocytes was comparable among negative and positive PD-L1 scores according to both 1% and 5% threshold values ( P >0.05). High PD-L1 expression is rare in AciCC, while PD-L1 expression is high in MEC. Our findings underline the importance of future screening for PD-L1 and PD-L2 before patients undergoing immunotherapies in all salivary gland tumors.

Impact of the COVID-19 pandemic on disease progression in patients with hepatobiliary and pancreatic cancer.

e16246 Background: The COVID-19 pandemic has posed challenges to healthcare systems, notably impacting cancer care. For patients with Hepatobiliary and Pancreatic Cancer, there has been a reported decline in median survival. The etiology of this decline, whether it is attributed to an escalation in disease severity or to delays in diagnosis and treatment remains unclear. Methods: This retrospective study analyzed the National Cancer Database (NCDB 2004-2020) data from 2018 to 2020. We compared time from diagnosis to initial treatment, AJCC (2017) TNM clinical stage distribution, and pathological variables suggestive of tumor aggression between the pre-pandemic and pandemic periods, as well as within COVID-19 positive (C19+) and negative (C19-) patients. Results: The study included 17,429 liver cancer (LC), 37,185 pancreatic cancer (PC), 1,684 gallbladder cancer (GC), and 3,651 intrahepatic biliary cancer (IBC) patient’s pre-pandemic, and 14,420 LC and 35,456 PC, 1,457 GC, and 3,792 IBC patients during the pandemic. The time to initial treatment did not significantly differ in the before and during the pandemic groups for all types of cancer. However, for GC, there was a significant increase in days to definitive surgery during the pandemic 54 ±73 days compared to pre-pandemic 28±53 days (p &lt; 0.01). There was also a notable increase in the time to initial treatment and definitive surgery for pancreatic cancer in C19+ patients (46±51, 118±104 days) compared to C19- patients (35±37, 97±89 respectively) (p &lt; 0.01). For LC and GC, there was a significant increase in late-stage diagnoses during the pandemic period. LC (stage III: 23.67% and stage IV: 21.10%) compared to pre-pandemic (stage III: 22.71% and stage IV: 19.02%, p &lt; 0.01). GC (stage IV: 77.0%) compared to pre-pandemic (stage IV: 71.85%, p &lt; 0.01). Lympho-vascular invasion rates and node positivity ratios in HC, GC, and IBC patients remained unchanged. For PC there was no change in late stage distribution and IBC there were no significant differences in overall stage distribution or lympho-vascular invasion rates. However, a significant increase in node positive/node harvested ratio was observed in stage III C19+ PC patients (0.308±0.322) compared to C19- (0.134±0.181, p &lt; 0.01). Conclusions: Cancer screening delays during the pandemic led to an increase in late-stage diagnoses for LC and GC but stage distributions for PC and IBC were largely unchanged. However, the pandemic's impact was subtly observed in the form of increased node positivity in stage III C19+ pancreatic cancer patients possibly due to their delay in initial treatment and surgery. There was also an increase in time to definitive surgery in gallbladder cancer. These findings underscore the importance of maintaining robust cancer care pathways, particularly for high-risk groups, to prevent adverse stage migration and ensure timely management, even in the face of global health emergencies.

Outcomes of Radical Hysterectomy for Early-Stage Cervical Carcinoma, with or without Prior Cervical Excision Procedure.

To investigate the impact of a prior cervical excisional procedure on the oncologic outcomes of patients with apparent early-stage cervical carcinoma undergoing radical hysterectomy. The National Cancer Database (2004-2015) was accessed, and patients with FIGO 2009 stage IB1 cervical cancer who had a radical hysterectomy with at least 10 lymph nodes (LNs) removed and a known surgical approach were identified. Patients who did and did not undergo a prior cervical excisional procedure (within 3 months of hysterectomy) were selected for further analysis. Overall survival (OS) was evaluated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control a priori-selected confounders. A total of 3159 patients were identified; 37.1% (n = 1171) had a prior excisional procedure. These patients had lower rates of lymphovascular invasion (29.2% vs. 34.9%, p = 0.014), positive LNs (6.7% vs. 12.7%, p < 0.001), and a tumor size >2 cm (25.7% vs. 56%, p < 0.001). Following stratification by tumor size, the performance of an excisional procedure prior to radical hysterectomy was associated with better OS even after controlling for confounders (aHR: 0.45, 95% CI: 0.30, 0.66). The rate of minimally invasive surgery was higher among patients who had a prior excisional procedure (61.5% vs. 53.2%, p < 0.001). For these patients, performance of minimally invasive radical hysterectomy was not associated with worse OS (aHR: 1.37, 95% CI: 0.66, 2.82). For patients undergoing radical hysterectomy, preoperative cervical excision may be associated with a survival benefit. For patients who had a prior excisional procedure, minimally invasive radical hysterectomy was not associated with worse overall survival.

Association between the expression of epithelial–mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer

BackgroundEpithelial–mesenchymal transition (EMT) is a key step in the development of colorectal cancer (CRC) that confers metastatic capabilities to cancer cells. The present study aimed to assess the immunohistochemical (IHC) expression and impact of EMT markers, including E-cadherin, Vimentin, β-catenin, and SMAD4, on the oncologic outcomes of CRC.MethodsThis was a retrospective review of 118 CRC patients. Tissue slides were retrieved from the slide archive and five tissue microarray construction blocks were constructed. IHC for E-cadherin, Vimentin, β-catenin, and SMAD4 was done. The main outcome was the association between abnormal marker expression and overall survival (OS), and disease-free survival (DFS).ResultsAdenocarcinomas accounted for 71.2% of tumors, whereas 25.4% and 3.4% were mucinous and signet ring cell carcinomas. The rates of lymphovascular invasion and perineural invasion were 72.9% and 20.3%, respectively. There was a positive, significant correlation, and association between the four markers. Abnormal expression of E-cadherin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.06). Abnormal Vimentin expression was associated with a significantly higher rate of distant metastasis (p = 0.005) and significantly lower OS and DFS (p < 0.0001). Abnormal expression of β-catenin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.15). Abnormal expression of SMAD4 was associated with significantly lower OS and DFS (p < 0.0001). Abnormal expression of all four markers was associated with a higher disease recurrence, lower OS, and lower DFS.ConclusionAbnormal expression of each marker was associated with lower OS, whereas abnormal expression of Vimentin and SMAD4 only was associated with lower DFS.

Effect of low uterine segment involvement on prognosis of early stage endometrial cancer.

Our aim is to investigate the effect of uterine lower segment involvement on prognosis of early-stage endometrial cancer cases diagnosed and treated in our clinic. The file records of 316 cases reviewed retrospectively.Only stage I (a and b, n=209) cases were investigated, because they were more homogeneous group. The lymphovascular invasion rate was found to be higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Adjuvant treatment requirement was higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Among stage Ia cases, the recurrence rate between 1 and 3 years was found to be higher in cases with uterine lower segment involvement (p = 0.001). Among the stage Ib cases, lymphovascular invasion was found to be higher in cases with uterine lower segment involvement (p < 0.001). The recurrence rate between 1 and 3 years was found to be higher in stage Ib compared to Ia (p = 0.01). Uterine lower segment involvement was found to be associated with high lymphovascular invasion rate in all stage I cases (p < 0.001). It was determined that the need for adjuvant treatment was higher in cases with uterine lower segment involvement (p < 0.001). It was determined that the probability of recurrence between 1 and 3 years was higher in cases with uterine lower segment involvement (p = 0.007). Uterine lower segment involvement is associated with increased lymphovascular invasion even in the early stages. It is an important risk factor for systemic spread such as lymphovascular invasion, myometrial invasion, and lymph node involvement.

Clinical Impact of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker for Predicting the Curability of Endoscopic Resection in Ulcerative Early Gastric Cancer

Introduction: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. Methods: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. Results: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). Conclusion: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.

Study on the diagnostic value of MDCT extramural vascular invasion in preoperative N staging of gastric cancer patients

BackgroundTo explore the diagnostic value of multidetector computed tomography (MDCT) extramural vascular invasion (EMVI) in preoperative N Staging of gastric cancer patients.MethodsAccording to the MR-defined EMVI scoring standard of rectal cancer, we developed a 5-point scale scoring system to evaluate the status of CT-detected extramural vascular invasion(ctEMVI), 0–2 points were ctEMVI-negative status, and 3–4 points were positive status for ctEMVI. Patients were divided into ctEMVI positive group and ctEMVI negative group. The correlation between ctEMVI and clinical features was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of ctEMVI for pathological metastatic lymph nodes and N staging, The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of pathological N staging using ctEMVI and short-axis diameter were generated and compared.ResultsThe occurrence rate of lymphovascular invasion (LVI) and proportion of tumors with a greatest diameter > 6 cm in the ctEMVI positive group was higher than that in the ctEMVI negative group (P < 0.05). Spearman correlation analysis showed a positive correlation between ctEMVI and LVI, N stage, and tumor size (P < 0.05). For ctEMVI scores ≥ 3,The AUC of ctEMVI for diagnosing lymph node metastasis, N stage ≥ N2, and N3 stage were 0.857, 0.802, and 0.758, respectively. The sensitivity, NPV and accuracy of ctEMVI for diagnosing N stage ≥ N2 were superior to those of short-axis diameter (P < 0.05), while sensitivity, specificity, PPV, NPV, and accuracy of ctEMVI for diagnosing N3 stage were superior to those of short-axis diameter (P < 0.05).ConclusionctEMVI has important value in diagnosing metastatic lymph nodes and advanced N staging. As an important imaging marker, ctEMVI can be included in the preoperative imaging evaluation of patients, providing important assistance for clinical guidance and treatment.

Orbital Exenteration for Craniofacial Lesions: A Systematic Review and Meta-Analysis of Patient Characteristics and Survival Outcomes.

The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings. Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.

COMPARISON OF CLINICAL PARAMETERS AND PATHOLOGICAL FEATURES OF INTESTINAL AND PANCREATOBILIARY HISTOLOGIC PHENOTYPES OF PERIAMPULLARY CARCINOMA

Background: Identification of the exact origin in large sized tumors of periampullary region is very difficult grossly and microscopically. The purpose of the study was to compare the two histological phenotypes of periampullary carcinoma in terms of their preoperative clinical parameters and pathological features. Methods: This was a prospective observational study done in patients diagnosed as periampullary carcinoma in specimen after pancreatoduodenectomy, between May 2018 and July 2019 at a Tertiary Teaching Hospital of Nepal. Relevant patient clinical characteristics, biochemical parameters including CEA and CA 19.9, immuno-histochemical markers (CK-20 and MUC-1) expression and histopathological details were recorded. Student t-test, ANOVA, median test, Kruskal Wallis test, binary logistic regression tests were used for analysis in SPSS version 20. P-value &lt; 0.05 was considered significant. Results: Thirty-nine patients with periampullary adenocarcinoma in Pancreatoduodenectomy specimen were included in the study with mean age of 58.6 years. Ampullary tumors (53.8%) were common in this study. Pancreatobiliary phenotype (61.5% versus 38.5%), was more common in head of pancreas and distal CBD tumors and was associated with significantly higher lymph node ratio (0.174 ± 0.173 versus 0.069±0.096), higher rates of lymphovascular invasion (66.7% versus 33.3%) and perineural invasion (75% versus 26.7%) on univariate analysis. On multivariate analysis, Perineural invasion was associated with Pancreatobiliary phenotype (Odds ratio of 10.46). Conclusions: Pancreatobiliary phenotype of periampullary tumors was associated with poor prognostic pathologic features like high lymph node ratio, lymphovascular invasion and perineural invasion. Perineural invasion had the strongest association of all.

Comparative Analyses of the Clinicopathologic Features of Short-Term and Long-Term Survivors of Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreatoduodenectomy.

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator

To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n=131); luminal B, 19.1% (n=40); HER2 enriched 13.4% (n=28); and triple negative, 4.8% (n=10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.

Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized. Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis. In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months). PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.

Clinical significance of squamous differentiation in upper tract urothelial carcinoma treated with radical nephroureterectomy.

451 Background: Upper tract urothelial carcinoma (UTUC) involving the renal pelvis/ureter is histologically similar to bladder cancer in morphological diversity. Although squamous differentiation (SD) is the most common variant in UTUC, the clinical significance of SD in UC has yet to be comprehensively elucidated given the rarity of the disease compared to bladder cancer. To assess the impact of SD on the prognosis of patients with UTUC undergoing radical nephroureterectomy (RNU). Methods: Among the 244 consecutive patients who underwent RNU at our single institution from May 2005 to October 2019, only patients who had histologically confirmed pure UC or UC with SD (UCSD) were included. SD required the presence of intercellular bridges or keratinization for diagnosis. Metastasis-free survival (MFS) and overall survival (OS) rates were retrospectively evaluated using Kaplan–Meier analysis and Cox regression analysis. Results: We identified 197 (87.9%) and 27 (12.1%) patients with pure UC and UCSD, respectively. No significant differences in age, sex, concomitant carcinoma in situ and tumour grade were observed between the groups. UCSD was significantly associated with an advanced tumour stage and a higher rate of lymphovascular invasion. With a median follow-up time of 58 months, the pure UC and UCSD groups had a 5-year MFS rate of 65.2% and 40.9% ( p=0.005) and a 5-year OS rate of 74.4% and 49.0% ( p=0.002), respectively. Multivariate analyses revealed that the presence of SD was significantly associated with MFS [hazard ratio (HR), 1.88; p=0.027] and OS (HR, 1.70; p=0.048). Conclusions: The patients with UCSD are at high risk for disease metastasis and short-term survival. SD in UC could be an independent predictor of poor prognosis after RNU for UTUC.

MUC1 Expressions and Its Prognostic Values in US Gastric Cancer Patients.

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and distant metastasis (32.0% vs. 5.0%; p = 0.017) compared with those with negative MUC1 expression. However, the differences in the pathologic features were not observed according to MUC2, MUC5AC, and MUC6 expression status. In early gastric cancer (EGC), patients with a high level of MUC1 expression showed a higher rate of lymphovascular invasion (71.4% vs. 21.4%; p = 0.026) and EGC meeting non-curative resection (85.7% vs. 42.9%; p = 0.061) than those with negative MUC1. In US GC patients, MUC1 expression is associated with aggressive pathological features, and might be a useful prognostic marker.

Expression of oncolong noncoding RNA taurine-upregulated gene-1 in colon cancer: A clinical study supported by in silico analysis.

Recent studies confirmed that dysregulation of long noncoding RNAs (lncRNAs) is a potential contributor to the development and progression of colon cancer. However, the prognostic value of these RNA molecules remains controversial. This study aimed to investigate the expression of taurine-upregulated gene-1 (TUG1) lncRNA in colon cancer and its clinical implications. A retrospective study on 47 formalin-fixed, paraffin-embedded samples of surgically resected primary colon cancer specimens was done. Total RNA purified from the colon cancer samples and noncancer adjacent tissue sections was quantified by real-time reverse transcription-polymerase chain reaction (qRT-PCR) to assess TUG1 relative expression levels normalized to GAPDH endogenous control. Also, in silico data analysis was applied. The relative expression levels were calculated using the LIVAK method. The survival rates were assessed using the Kaplan-Meier curves and the Cox proportional model. P < 0.05 was considered statistically significant. TUG1expression in the colon cancer specimens was significantly overexpressed (median = 21.50, interquartile range [IQR]: 7.0-209.2; P = 0.001) relative to the noncancerous tissues. In silico analysis confirmed TUG1 upregulation in colon carcinoma (median = 13.92, IQR: 13.5-1432). There were no significant associations between TUG1 expression and clinicopathological characteristics, such as the site, grade, stage, histopathological type, or the rates of lymphovascular invasion and relapse. Similarly, Kaplan-Meir and Cox multivariate regression analyses showed that TUG1 expression could not predict the overall survival and progression-free survival in colon cancer patients of our population. This study confirms the overexpression of TUG1 lncRNA in colon cancer tissues. Larger sample size is warranted to further elucidate the specific role of TUG1 in colon cancer.

Clinical Outcomes of 160 Patients with Clinically Node-Negative Merkel Cell Carcinoma after Wide Excision and Sentinel Lymph Node Biopsy

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with high nodal metastasis rates. Studies regarding the prognostic significance of sentinel lymph node (SLN) status differ. We evaluated the outcomes of MCC patients after wide excision + sentinel lymph node biopsy (WE+SLNB). METHODS: A retrospective review of 160 MCC patients who underwent WE+SLNB at our institution (April 2005 through July 2021) was performed. Clinicopathologic variables and outcomes were assessed. RESULTS: Sixty-four patients (40%) were SLNB(+), 92 (58%) were SLNB(–); 4 did not map. SLNB(+) patients were more likely to be female (42% vs 27%, p = 0.05), have larger primary tumors (13.0 vs 7.4 mm, p < 0.001), higher rates of lymphovascular invasion (61% vs 36%, p = 0.006), and infiltrative growth patterns (72% vs 62%, p = 0.048). Most SLNB(+) patients received further nodal therapy: completion lymph node dissection (CLND, n = 9), CLND with radiotherapy (n = 6), or radiotherapy (n = 26). Patients who underwent CLND (n = 15, 23%) were more likely to have SLNs with extracapsular extension (40% vs 14%, p = 0.02) and receive systemic therapy (80% vs 51%, p = 0.07), and less likely to receive nodal basin radiotherapy (40% vs 71%, p = 0.04) than those who did not undergo CLND. At a median follow-up of 32 months, 40% of SLNB(–) patients recurred vs 48% of SLNB(+) patients (with CLND, 67%; without CLND, 43%; Table). Recurrence-free survival for SLNB(–), SLNB(+) without CLND, and SLNB(+) with CLND patients was 61.6, 35.6, and 26.8 months, respectively. Table. - Outcomes of MCC Patients Who Underwent WE+SLNB Outcomes Total cohort (n = 160) (+) SLNB (n = 64) (–) SLNB (n = 92) With CLND (n=15) Without CLND (n=49) Overall survival, mo, median (range) 89 (1–199) 35 (0–40) 69 (0–69) 105 (0–199) Recurrence-free survival, mo, median (range) 39 (25–69) 27 (13–39) 36 (20–69) 62 (19–X) Any recurrence, N (%) 69 (43) 10 (67) 21 (43) 37 (40) Status at last follow-up, N (%) Alive, no evidence of disease 94 (58.9) 5 (33.3) 28 (57.1) 56 (63.0) Alive with disease 16 (10.0) 3 (20.0) 5 (10.2) 8 (8.7) Deceased 50 (31.3) 7 (46.7) 16 (32.7) 26 (28.3) CONCLUSION: SLNB(–) patients had better outcomes than SLNB(+) patients. Among the SLNB(+) patients, CLND was associated with worse outcomes. Work to evaluate trends in the multimodal treatment of SLNB(+) MCC patients and the impact on outcomes is underway.

The complementary role of lymphovascular invasion and perineural invasion in the TNM staging process of rectal cancer.

The aim of this study is to clarify the association between lymphovascular invasion (LVI) and/or perineural invasion (PNI) and the clinical characteristics and prognostic importance of rectal cancer, to provide a basis for early adjuvant treatment of rectal cancer. We retrospectively analyzed patients diagnosed with rectal cancer. This study involved rectal cancer tissue samples were obtained by surgical methods. Data on histological form, tumor classification, tumor size, gross growth pattern, blood and lymphatic vessel invasion, and PNI of the slice by HE staining were obtained from pathological examination. Immunohistochemical analysis of tissue samples was performed to determine p53 and EGFR expressions. There were 330 rectal cancer patients included in the study. LVI and/or PNI can be used as a high-risk factor for the prognosis of rectal cancer, predict prognostic survival, and guide adjuvant therapy. The detection rates of LVI and PNI were 32.1% and 16.1%. Differentiation grade, Union for International Cancer Control staging, tumor-lymph node-metastasis staging are significantly related to LVI or PNI. Multivariate logistic regression analysis shows that poor differentiation and N ≥ 1 can be used as independent risk factors and predictive factors for LVI. At the same time, poor differentiation and T > 3 is an independent risk factor for PNI. Only poor differentiation is the risk factor for poor prognosis in Cox risk regression analysis. In addition, the simultaneous occurrence of LVI and PNI is an independent prognostic factor.

Solid Pseudopapillary Neoplasms of the Pancreas Across Races Demonstrate Disparities with Comparably Good Prognosis.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare with low-grade malignancy and unclarified clinicopathological features. This study aimed to examine their characteristics and re-evaluate current treatments. Databases from three sources were screened for patients with SPNs. We compared the perioperative variables, clinical data, overall survival (OS), and prognostic factors for recurrence among the three corresponding cohorts. We identified 286 patients diagnosed with SPNs between 1988 and 2020. Patients were mostly women (81%; median age: 38years), and peak incidence was observed in women of 20-29years of age. SPNs had a peak incidence in Asian men at 50-59years of age (p = 0.002) and a delayed peak incidence in Asian women at 30-39years of age (p < 0.001). Treatment strategies differed significantly across the institutions and included variations in the number of harvested lymph nodes and rates of vascular resection. Lymph node positivity was the only predictor of postoperative recurrence (odds ratio, 2.2; 95% confidence interval, 1.38-2.99; p = 0.007). Higher rates of lymphovascular invasion (p = 0.02), perineural invasion (p < 0.001), and R1 margin involvement (p < 0.001), as seen in one institution, did not result in poorer long-term survival in terms of the overall (p = 0.43), SPN-specific (p = 0.69), and recurrence-free survivals (p = 0.067). In contrast to previous findings that SPNs are prevalent in young women, a racial predilection for middle-aged Asian men and a delayed female peak incidence were noted. Parenchyma-preserving pancreatectomy may be an acceptable treatment. Non-radical surgery may be appropriate in patients with multiple comorbidities.

Increased Expression of LEF1 and β-Catenin in Invasive Micropapillary Carcinoma of the Breast is Associated With Lymphovascular Invasion and Lymph Node Metastasis.

Invasive micropapillary breast carcinoma (IMPC) is a rare breast cancer subtype characterized by small tumor cell clusters with loss of stromal attachment, an inside-out growth appearance, and lymphotropism. IMPC is associated with high incidence of lymphovascular invasion (LVI) and lymph node metastasis. Activated Wnt signaling has been implicated in the metastasis of other aggressive breast tumors, including triple-negative and basal-like carcinomas. In this study, we tested whether activated Wnt signaling could be detected in IMPC. Upon ligand binding, the central mediator of the Wnt pathway, β-catenin, accumulates in the cytosol and translocates to the nucleus where it forms a complex with lymphoid enhancer-binding factor 1 (LEF1) to regulate transcription. We performed immunostaining for β-catenin and LEF1 on a well-annotated cohort of 40 breast tumors and nodal metastases displaying micropapillary histopathology. Strong nuclear accumulation of β-catenin was not observed, however a dim cytosolic and/or nuclear accumulation of β-catenin was sometimes seen in IMPC and this expression pattern was significantly associated with nodal metastasis. β-catenin expression correlated with the upregulation of LEF1 in IMPC. LEF1 expression was detected in 26 of 40 (65%) cases and was specifically enriched at the invasive front of the tumor and in tumor clusters undergoing LVI. Detection of LEF1 expression in the primary tumor was associated with an increased rate of LVI, lymph node metastasis, and disease relapse. LEF1 and β-catenin expression levels were significantly higher in metastases compared with primary tumors. In summary, this study demonstrates an association between the upregulation of β-catenin/LEF1 and the metastasis of IMPC.