Presence Of Lymphovascular Invasion Research Articles

Preoperative brachytherapy of early-stage cervical cancer: A multicenter study by the SFRO brachytherapy group

ObjectiveTo report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC). MethodsA retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4–8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors. ResultsA total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84–91), 98% [95% CI (96–99), and 92% [95% CI (87–95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS. ConclusionPBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.

“Find Your Y”: histological differences in early stage (pT) and post-treatment (ypT) oesophageal adenocarcinoma with implications for salvage endoscopic resection

AimsCurrent guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited....

Metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma without neoadjuvant therapy

PurposeThis research aimed to clarify the metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma and to investigate appropriate strategies for lymph node dissection.MethodsPatients with thoracic esophageal squamous cell carcinoma receiving esophagectomy from December 2020 to April 2024 were retrospectively analyzed. Risk factors for subcarinal, right and left recurrent laryngeal nerve lymph nodes metastasis were determined by chi-square test and multivariate logistic regression analysis. We visualized the metastasis rates of these specific lymph nodes based on the different clinicopathological characteristics. Correlation between subcarinal, right and left recurrent laryngeal lymph nodes metastasis and postoperative complications were also analyzed.ResultsA total of 503 thoracic esophageal squamous carcinoma patients who underwent esophagectomy were enrolled. The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes were 10.3%, 10.3%, and 10.9%, respectively. The lymphovascular invasion status and tumor location were the significant predictors for subcarinal and right recurrent laryngeal nerve lymph nodes metastasis, respectively (P < 0.001 and P = 0.013). For left recurrent laryngeal nerve lymph node metastasis, younger age (P = 0.020) and presence of lymphovascular invasion (P = 0.009) were significant risk factors. Additionally, pulmonary infection is the most frequent postoperative complication in patients with dissection of subcarinal, right and left recurrent laryngeal lymph nodes. There was no significant difference in the incidence of anastomotic leakage (P = 0.872), pulmonary infection (P = 0.139), chylothorax (P = 0.702), and hoarseness (P = 0.179) between the subcarinal lymph node dissection cohort and the reservation cohort. The incidence of hoarseness significantly increased in both right (P = 0.042) and left (P = 0.010) recurrent laryngeal nerve lymph nodes dissection cohorts compared by the reservation cohorts, with incidence rates of 5.9% and 6.7%, respectively.ConclusionsThe metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma were all over 10%. The dissection of subcarinal lymph nodes does not increase postoperative complications risk, while recurrent laryngeal nerve lymph nodes dissection significantly increases the incidence of hoarseness. Thus, lymph node dissection of subcarinal lymph nodes should be conducted routinely, while recurrent laryngeal nerve lymph nodes dissection may be selectively performed in specific patients.

Radiographic predictors of muscle-invasive upper tract urothelial cancer

Introduction: Accurate diagnostic staging of upper tract urothelial cancer (UTUC) is challenging. Endoscopic staging is limited by its ability to provide adequate sampling of deeper layers of the ureter and renal pelvis. Further ability to accurately predict invasive disease would aid in better selecting the appropriate treatment for patients. We aimed to analyze the ability of preoperative cross-sectional radiologic findings to predict pathologic outcomes, including tumor grade, muscle-invasive disease, and presence of lymphovascular invasion (LVI). Methods: All patients diagnosed with localized UTUC (cN0M0) who underwent nephroureterectomy between February 2012 and December 2018 in Manitoba, Canada, were identified. Preoperative radiologic characteristics, including the presence and severity of hydronephrosis, as well as tumor location were recorded. Patients’ and pathologic characteristics were also recorded. Logistic regression analysis was used to assess the association between radiologic variables and pathologic outcomes at radical surgery. Results: A total of 112 pathology reports of patients with UTUC were obtained. The median age was 70 years (range 50–87), and 58.8% of patients were men. On univariate analysis, ureteric location on computed tomography (odds ratio [OR] 2.240, 95% confidence interval [CU] 1.049–4.783, p=0.037) and presence of hydronephrosis (OR 2.455, 95% CI 1.094–5.506, p=0.0029) were each independently associated with locally invasive disease (&gt;pT2). No radiologic variables were found to be a predictor of adverse pathology on multivariable analysis. Only the presence of hydronephrosis was associated with high-grade disease on univariate analysis (OR 2.533, 95% CI 1.083–5.931, p=0.032). Conclusions: Our findings suggest a limited role for cross-sectional imaging in predicting the presence of high-grade disease, LVI, or locally advanced disease in UTUC.

Programmed death ligand I (PDL-1) Expression in renal cell carcinoma: A retrospective cohort study

Background and objectives: Inhibition of programed death -1and programed death ligand-1 pathway enhances antitumor activity of T lymphocytes, therefore, provides a new strategy for tumor treatment utilizing immunotherapy. The aim of this study to assess the frequency of programed death ligand-1 expression in renal cell carcinoma by using the immunohistochemistry and to correlate the results the clinicopathologic parameters. Methods: This is a cross sectional retrospective study performed in Duhok City from 2017-2022 on fifty-four formalin fixed paraffin embedded blocks of nephrectomy specimens diagnosed as renal cell carcinoma and collected from central lab of Duhok and some private labs. Two sections were prepared from each block, one section was stained with hematoxylin and eosin for histological analysis and the other one was used for immunohistochemical assessment of programed death ligand-1then the results were correlated with various clinicopathological parameters. Results: Programed death ligand -1; membranous expression was positive in 19 cases (35.2%) of renal cell carcinoma out of 54 cases. There was no significant correlation between programed death ligand -1 expression and age (p= 0.991), gender (p= 0.272), multifocality (p= 0.607), tumor size (p= 0.796), histological subtype (p= 0.107), tumor stage (p= 0.546), nuclear grade (p= 0.781), surgical margins involvement (p= 0.119) and lymphovascular invasion (p= 0.4), but there was statistically significant correlation with nodal metastases (p= 0.039). Conclusion: Programmed death ligand -1/ Combined positive score was ?1 in about one third (35.2%) of renal cell carcinoma cases and this result can be utilized for the provision of immune checkpoint inhibitor (ICIs), regardless the age, gender, histological type, stage, nuclear grade, and the presence of lymphovascular invasion (LVI).

Association between lymphovascular invasion (LVI) and prognostic factors in breast cancer.

Association between lymphovascular invasion (LVI) and prognostic factors in breast cancer.

Risk factors for lymph node metastasis in T2 colorectal cancer: a systematic review and meta-analysis.

Lymph node metastasis (LNM) occurs in 20-25% of patients with T2 colorectal cancer (CRC). Identification of risk factors for LNM in T2 CRC may help identify patients who are at low risk and thereby potential candidates for endoscopic full-thickness resection. We examined risk factors for LNM in T2 CRC with the goal of establishing further criteria of the indications for endoscopic resection. MEDLINE, CENTRAL, and EMBASE were systematically searched from inception to November 2023. Studies that investigated the association between the presence of LNM and the clinical and pathological factors of T2 CRC were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Certainty of evidence (CoE) was assessed using the GRADE approach. Fourteen studies (8349 patients) were included. Overall, the proportion of LNM was 22%. The meta-analysis revealed that the presence of lymphovascular invasion (OR, 5.5; 95% CI 3.7-8.3; high CoE), high-grade tumor budding (OR, 2.4; 95% CI 1.5-3.7; moderate CoE), poor differentiation (OR, 2.2; 95% CI 1.8-2.7; moderate CoE), and female sex (OR, 1.3; 95% CI 1.1-1.7; high CoE) were associated with LNM in T2 CRC. Lymphatic invasion (OR, 5.0; 95% CI 3.3-7.6) was a stronger predictor of LNM than vascular invasion (OR, 2.4; 95% CI 2.1-2.8). Lymphovascular invasion, high-grade tumor budding, poor differentiation, and female sex were risk factors for LNM in T2 CRC. Endoscopic resection of T2 CRC in patients with very low risk for LNM may become an alternative to conventional surgical resection. PROSPERO, CRD42022316545.

Abstract PO2-23-01: Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery

Abstract Background: Breast conserving surgery (BCS), which became the mainstay of breast cancer surgery, both cosmesis and margin negativity are significant issues. Firstly, it is well known that negative resection margin is crucial for reducing local recurrence after BCS. Therefore, there has been numerous attempts to secure negative margin, such as specimen mammography, frozen section margin analysis, and cavity margin shaving. Regarding cosmesis, wider excision to secure negative margin could disrupt cosmesis especially in Asian patients with relatively smaller breast, and minimizing excision volume is necessary for optimal cosmetic outcome. Our center adopted the concept of selective cavity margin shaving (SCMS) to achieve negative margin while optimizing cosmetic result. Method: 606 female patients with non-metastatic, unilateral breast cancer were prospectively collected and underwent BCS with SCMS from October, 2012 to December, 2020. The medical record was retrospectively reviewed, and we assessed positive margin rate and local recurrence. During BCS, the surgeon excised gross margin of 1~2cm around the cancer, and assessed the proximity of the margin through gross examination. If sufficient margin was not obtained, cavity shaving was performed in the close margin, while shaving from retrieved specimen was conducted on the sufficient margin side. Additionally, circumferential margin frozen analysis was carried out, and further excision was performed until a negative margin was achieved or when only focal DCIS involvement remained. Result: The mean ± SD age of the patients was 52.47 ± 9.92 years and mean follow-up period was 59.98 ± 26.59 months. 56 patients (9.24%) received neoadjuvant chemotherapy. 123 patients (20.29%) got positive margin for invasive cancer or DCIS in frozen section margin analysis and 97 patients (16.01%) underwent intraoperative re-excision. There was discordance between frozen and permanent section margin analysis in 48 patients (7.92%), and 7 patients (1.16%) underwent post-operative re-excision operation. Local recurrence occurred in 11 patients (1.82%), which is significantly lower compared to previously reported outcomes after BCS. Presence of lympho-vascular invasion, neoadjuvant chemotherapy, and margin involvement of invasive cancer in permanent section analysis were strongly related with local recurrence. Conclusion: In conclusion, SCMS and frozen section margin analysis demonstrated low positive margin rate and reduced re-excision rate. The local recurrence was also lower compared to conventionally reported rate after BCS. Selective cavity margin shaving is an oncologically safer and effective surgical method with minimized cosmetic deformity. Table 1. Baseline patient characteristics Table2. Univariate and multivariate analysis of factors associated with local recurrence Table2. Univariate and multivariate analysis of factors associated with local recurrence by Cox proportional hazard model. Citation Format: Dabin Kim, Zisun Kim, Sung Mo Hur, Cheol wan Lim. Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-01.

Abstract PO5-26-12: Optimizing Treatment Decisions in Microinvasive Ductal Carcinoma in Situ: Evaluating the Need for Surgical Axillary Staging

Abstract Background: Surgical axillary staging is often debated in patients with microinvasive ductal carcinoma in situ (T1mi) due to the low occurrence of nodal metastasis. Axillary surgery (ASx) is associated with risks like seroma, wound complications, lymphedema, and sensory deficits. This study aims to assess the utility of surgical axillary staging in clinically node-negative (cN0) T1mi breast cancer patients and provide insights for optimizing high value surgical treatment and subsequent decision-making. Methods: This retrospective cohort study analyzed data from the National Cancer Database (NCDB) to investigate axillary status of patients with cT1mi breast cancer between 2012 and 2019. Patient demographics, clinical characteristics, treatment methods and pathologic findings were collected. Comparisons were made between those who did and did not undergo ASx, and of those who did, between patients who were pathologically node-positive (pN+) vs. node-negative (pN-). Results: Of 10,843 patients analyzed, 9,220 (85.0%) underwent ASx while 1,623 (15.0%) did not. Mean age of patients undergoing ASx and those who did not was 59.2±11.2 and 66.3±12.8 years, respectively (p&amp;lt; 0.001). On univariate analysis, other factors associated with undergoing ASx were having private insurance, fewer medical comorbidities, having a HER2+ or triple negative phenotype, higher grade, presence of lymphovascular invasion and undergoing mastectomy (all p&amp;lt; 0.05). Sentinel lymphadenectomy was performed in 83% of patients while axillary lymph node dissection (ALND) was performed in 17% of patients. Final pathology demonstrated an upgrade to a true invasive cancer (T1 or greater) in 29.3% of cases. Of 9,069 patients who underwent ASx with known pathologic nodal status, 8,512 (93.9%) were pN- and 557 (6.1%) were pN+. Factors independently associated with increased odds of having positive nodes were younger age (OR 1.02, 95% CI 1.01-1.03, p&amp;lt; 0.001), Black race (OR 1.51, 95% CI 1.12-2.10, p=0.007), lymphovascular invasion (OR 13.72, 95% CI 10.25-18.36, p&amp;lt; 0.001), and undergoing mastectomy (OR 1.98, 95% CI 1.57-2.51, p&amp;lt; 0.001). Among the pN+ patients, only 64 (0.7%) had ≥3 total positive nodes and would require ALND. On subset analysis of the 4,190 patients undergoing mastectomy, 244 (5.8%) did not undergo ASx, while 3,946 (94.2%) did, of whom 373 (9%) were pN+. Regarding adjuvant treatments in this group, more patients who underwent ASx received chemotherapy (12% v. 8%, p&amp;lt; 0.001), and among those who did undergo surgery those who were pN+ were much more likely to receive chemotherapy (58% v. 12%, p&amp;lt; 0.001). However, similar proportions of patients who did and did not undergo ASx received adjuvant radiation (5% v. 4%, p=0.65), while, as expected, among those undergoing ASx, a higher proportion who were pN+ underwent radiation (32% v. 5%, p&amp;lt; 0.001). Conclusion: Surgical axillary staging for T1mi breast cancer is common, but many patients are node-negative. More patients are undergoing ALND than necessary based on pathology. Nodal status influences adjuvant therapy decisions. Identifying factors linked to upgrade and higher pN+ probabilities can enable personalized surgical treatments, reducing morbidity for most patients. Citation Format: Christian Lava, Karen Li, Lauren Berger, Daisy Spoer, Lindy Rosal, Austin Williams, Monika Masanam, Ian Greenwalt, Jennifer Son, Lucy De La Cruz. Optimizing Treatment Decisions in Microinvasive Ductal Carcinoma in Situ: Evaluating the Need for Surgical Axillary Staging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-12.

Abstract PO1-22-10: Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases

Abstract Background: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of and factors associated with local recurrence (LR) after IBR. Methods: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. Results: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p &amp;lt; 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p=0.002). Conclusions: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR. Citation Format: Akiko Ogiya, Naomi Nagura, Ayaka Shimo, Hiroko Nogi, Kazutaka Narui, Hirohito Seki, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Kohei Akazawa, Tadahiko Shien. Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-10.

Endoscopic submucosal dissection for rectal neuroendocrine tumours: A multicentric retrospective study

IntroductionEndoscopic Submucosal Dissection (ESD) has been reported as a feasible and effective treatment for Rectal Neuroendocrine Tumours (R-NETs). However, most of the experience on the topic comes from retrospective tertiary centre from Eastern Asia. Data on ESD for R-NETs in Western centres are lacking. Materials and MethodsThis is a retrospective study, including patients who underwent endoscopic resection of R-NETS by ESD between 2015 and 2020 in Western Centres. Important clinical variables such as demographic, size of R-NETs, histological type, presence of lymphovascular invasion or distant metastasis, completeness of the endoscopic resection, recurrence, and procedure related complications were recorded. Results40 ESD procedure on R-NETs from 39 patients from 8 centres were included. Mean R-NETs size was 10.3 mm (SD 4.01). Endoscopic en-bloc resection was achieved in 39/40 ESD (97.5 %), R0 margin resection was obtained in 87.5 % (35/40) of the procedures, one patient was referred to surgery for lymphovascular invasion, two procedures (5 %) reported significant episodes of bleeding, whereas a perforation occurred in one case (1/40, 2.5 %) managed endoscopically. Recurrence occurred in 1 patient (2.5 %). ConclusionESD is an effective and safe treatment for R-NETs in western centres.

Emergency resection for stage II colon cancer: patterns of recurrence and prognostic factors

Background: The prognosis in colon cancer patients who undergo emergency curative resection remains uncertain. This study aimed to analyze the oncological outcomes in stage II colon cancer patients who underwent emergency or elective colon resection and identify the prognostic factors for recurrence following emergency resection. Methods: Patients in this study underwent curative resection for stage II colon cancer between March 2008 and December 2020. Based on surgical condition, patients were divided into two groups: emergency and elective. The two groups were compared regarding clinicopathological features and postoperative recurrence. Prognostic factors for recurrence were analyzed in the emergency resection group. Results: Among 161 patients, 60 and 101 patients were emergency group and elective group, respectively. The emergency group had significantly lower adequately harvested lymph nodes than the elective group (p=0.02). The emergency group had significantly poorer disease-free survival compared to the elective group (p=0.019). The most common recurrence site was local recurrence. No statistically significant difference was observed between the two groups in recurrence site. The presence of lymphovascular invasion and clinical perforation were prognostic factors for recurrence in the emergency resection group. Conclusion: Emergency resection for stage II colon cancer is associated with poor disease-free survival compared to elective resection. The prognosis may improve by performing appropriate radical surgery including extensive lymph node dissection. Adjuvant chemotherapy should be performed following emergency surgery for stage II colon cancer, especially when lymphovascular invasion or colonic perforation is identified.

Differentiated Thyroid Cancer in Children and Adolescents: 12-year Experience in a Single Center.

Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of our study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence. We conducted a retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at our center. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, 17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) were submitted to RAI. The mean follow-up time was 5.7 ± 3.1 years. Overall, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs 0.0% (0/6), p=0.031]. An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.

Lympho-vascular invasion in oral cavity cancers – A bridge between tumour biology and clinical outcomes

ObjectiveVarious histo-pathological prognostic factors have been identified in oral cavity squamous cell carcinomas (OCSCC). One such factor is the status of lympho-vascular invasion (LVI). We carried out this analysis to evaluate the association of LVI with other prognostic factors and the clinical outcomes. MethodsData of patients with OCSCC who underwent curative intent surgery from January-2017 to December-2019 at our institute were retrospectively evaluated. The association of LVI with various tumour-node related prognostic factors and its effect on overall and disease-free survival (OS, DFS) were analyzed. Resultsof the total 234 patients, 71 % (166) had Bucco-alveolar-complex primary. 62.8 % (147) had locoregionally advanced disease. 91.5 % (214) required adjuvant treatment.The LVI positivity was 77.4 %, 63.3 % in tumour size >3cm/<3 cm, 85 %, 59.7 % in depth of infiltration >1cm/<1 cm, 82.4 %, 57.6 % in T3-T4/T1-2, 91.9 %, 59.9 % in grade 3/others and 96.8 %, 13.8 % in perineural invasion present/absent, respectively (p < 0.05). In the presence of LVI, lymph node positivity was 60.6 %, N2–N3 were 41.9 % and extra-capsular extension was 26.9 % as compared to LVI negative – 5.4 %, 5.4 % and 4.1 % respectively (p < 0.05).With median follow up of 37.3 months, 2year OS and DFS were 76.6 % and 75.5 % respectively. The 2year OS and DFS for the LVI-positive group were 70.4 % and 69.3 % compared to 90.6 % and 89.3 % for LVI-negative (p = 0.00). Loco-regional and distal (any) recurrence was seen in 20.9 % (49) and 7.3 % (17), the same for LVI-positive was 25.6 % (41) and 10 % (16) compared to 10.8 % (8) and 1.4 % (1) for LVI-negative (p < 0.05). ConclusionIn oral cavity cancers, there is positive association of LVI with various tumour-node related prognostic factors and clinical outcomes.

Immunohistochemical evaluation of tumor hypoxia and angiogenesis: Pathological significance and prognostic role in head and neck squamous cell carcinomas

Objectives: Tumor hypoxia and angiogenesis have been implicated in therapeutic resistance of head and neck squamous cell carcinomas (HNSCCs). Immunohistochemical evaluation of hypoxia-inducible factor-1 alpha (HIF-1 α), a hypoxia transcription factor, and vascular endothelial growth factor (VEGF), a hypoxia-responsive pro-angiogenic factor, can be exploited for prognostication and guiding treatment intensification or de-escalation decisions in HNSCC patients. The purpose of the study is to evaluate the immunohistochemical expression patterns of HIF-1 α and VEGF and the microvessel density (MVD) for angiogenesis in HNSCC and assess their pathological significance and prognostic role. Materials and Methods: In this cross-sectional study, immunohistochemical expression of HIF-1 α, VEGF, and MVD through Cluster of Differentiation (CD31) was evaluated in paraffin-embedded tumor resection tissue of 44 patients with HNSCC. Associations among HIF-1 α, VEGF, and MVD with clinicopathological variables were assessed. Statistical Analysis: For assessment of association between HIF-1α, VEGF and MVD by CD 31 immunohistochemical markers and other clinicopathological variables Pearson’s chi-square test and Fisher’s exact tests were used. Analysis of survival was done using Kaplan-Meier statistics. Also, the univariate and multivariate analysis were performed using the Cox proportional hazard regression model for the calculation of hazard ratios. Results: Nuclear expression of HIF-1 α showed significant association with MVD (P = 0.007) and cytoplasmic expression of HIF-1 α with histologic grade (P = 0.03). Overexpression of HIF-1 α was more frequent in T3/T4 stage. In addition to cytoplasmic staining, VEGF showed a unique nuclear expression pattern in four cases of advanced disease with nodal metastasis. Logistic regression analysis showed tumors with nuclear overexpression of HIF-1 α to have increased MVD (P = 0.05), and tumors with higher MVD to have a presence of lymphovascular invasion (P = 0.014). Multivariate analysis showed HIF-1 α nuclear overexpression to be significantly associated with decreased survival of patients (P = 0.05). Conclusions: Immunohistochemical overexpression of HIF-1 α and MVD quantification can serve as cost-effective tools for prognostication and treatment modification of HNSCC patients in resourcelimited settings.

Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation.

The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion.

Immunochemistry-based quantification of tumor-infiltrating lymphocytes and immunoscore as prognostic biomarkers in bladder cancer

BackgroundTumor-infiltrating lymphocytes (TILs) and the derived immunoscore (IS) have gained considerable attention over the last decade as prognostic markers in many solid cancers. However, in bladder cancer (BC), their prognostic value is not clearly established.MethodsThe present study aimed to quantify the TILs rates in BC, assess the derived immunoscore, and investigate their prognostic value. An immunochemistry-based quantification of the different subtypes of TILS was performed on paraffin-embedded blocks from patients with invasive urothelial carcinoma of the bladder. We have assessed the rates of TILs, respectively, on peri-tumoral (PT) and intra-tumoral (IT) areas and calculated for each case the corresponding IS which is the index: CD8+/CD3+ TILs. The IS was then classified as low (I0, I1) or high (I2, I3, I4). We included 30 cases in the analysis.ResultsThe median age of patients was 65 years with a sex ratio of 9. TILs densities and distribution were significantly variable between IT and PT areas CD3+ (p = 0.03) and CD8+ (p = 0.004) with the highest rates on the PT areas. In univariate analysis, a low density of CD8+ TILs was significantly associated with an advanced age (p = 0.05), with the presence of lympho-vascular invasion (p = 0.02) and with the absence of specific histological subtype (p = 0.05). A low immunoscore was significantly associated with the presence of lympho-vascular invasion (p = 0.004). No significant association was found between TILs subpopulations, the IS, and the other clinicopathological and survival data. The overall survival (OS) and disease-free survival (DFS) medians were slightly superior in highly T (CD3+/CD8+)-cell infiltrated tumors as well as tumors with a high IS densities. However, the univariate analysis showed that TILs and immunoscore did not impact overall survival (OS) and disease-free survival (DFS).ConclusionTILs and immunoscore might be effective prognostic tools in BC. However, standardized quantification methods and further investigation on larger samples are highly recommended to definitively attest the prognostic value of TILs and IS in BC.

P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer.

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Cellular senescence in testicular cancer. Is there a correlation with the preoperative markers and the extent of the tumor? An experimental study.

The aim of this experimental study is to investigate the correlation between the presence of senescent cells and the tumor size, the lymphovascular invasion (LVI), the invasion of rete testis (RTI), the preoperative tumor markers or pathological stage in patients who underwent orchiectomy for malignant purposes. This experimental study included patients with a history of radical orchiectomy performed from January 2011 to January 2019. The testicular tissue specimens underwent an immunohistopathological process for the detection of the presence of cellular senescence. Besides, the tumor size, the histopathological type, the pathological stage of the tumor and the presence of Lymphovascular (LVI) or rete testis (RTI) invasions were also recorded. Additionally, the preoperative serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were recorded. After the completion of immunohistochemical analysis, the rate of senescent cells in each specimen was also recorded. The mean senescent cell rate was estimated to be 14.11 ± 11.32% and 15.46 ± 10.58% in patients with presence of LVI or absence of LVI, respectively (p = 0.46). The mean senescent cell rate was calculated at 18.13±12.26% and 12.56 ± 9.38% (p = 0.096) in patients with presence of RTI or absence of RTI, respectively. The mean senescent cell rate in the pT1 group was calculated at 14.58 ± 9.82%, while in T2 and T3 groups the mean senescent cell rate was estimated to be 15.22 ± 12.03% and 15.35 ± 14.21%, respectively (p = 0.98). A statistically significant correlation was detected between the senescence rate and the tumor size (Pearson score 0.40, p = 0.027) and between the rate of senescent cells and the preoperative level of lactate dehydrogenase (LDH) (Pearson score -0.53, p = 0.002). The presence of cellular senescence was correlated with the extent of the testicular tumor in terms of tumor size as well as the preoperative level of the LDH serum marker.