Presence Of Perineural Invasion Research Articles

Perineural invasion in cervical cancer.

Perineural invasion in cervical cancer.

Correlation between radiological, macroscopic and microscopic depth of invasion in oral squamous cell carcinoma: A prospective study using contrast-enhanced computed tomography.

Correlation between radiological, macroscopic and microscopic depth of invasion in oral squamous cell carcinoma: A prospective study using contrast-enhanced computed tomography.

The impact of surgical margins in managing regional metastases in cutaneous squamous cell carcinoma of the head and neck.

Regional metastasis occurs in 5% of cutaneous squamous cell carcinoma (cSCC). The aim of this study is to assess the impact of margin status of regional metastases on survival. A retrospective review of 401 patients with nodal metastases from cSCC. Margin status of nodal metastases was classified as clear (>1 mm), close (<1 mm), or involved. Cox regression and Kaplan-Meier methods were used to assess associations with overall and disease-specific survival (OS and DSS). Of the 401 patients with nodal metastases (median age 75, 85.3% male), 43.6% had involved margins, 27.4% had close margins, and 28.9% had clear margins. Involved margins were significantly associated with reduced OS and DSS on univariable analysis. Multivariable analysis confirmed that involved margins independently predicted worse DSS (HR 1.92, 95% CI 1.15-3.19, p = 0.01). Other independent prognostic factors included size of deposit (HR 1.02, 95% CI 1.01-1.04, p < 0.001), number of deposits (HR 1.05, 95% CI 1.02-1.08, p < 0.001), and the presence of perineural invasion (HR 1.84, 95% CI 1.14-2.98, p = 0.01). Clear surgical margins during the removal of regional metastases of cSCC improves survival outcomes. This study highlights the importance of careful preoperative evaluation to achieve a complete (R0) surgical resection. Level 3 Laryngoscope, 2025.

A Prospective Study to Evaluate the Association of Sensory Dysregulation and Adverse Pathologic Features in Oral Tongue Cancers

Abstract Objectives To correlate sensory dysfunction with adverse pathologic factors for tongue cancers and determine the survival prognosticators. Methods We prospectively collected data on the pain sensation (Brief Pain Inventory), gustation (NIH Taste Intensity Test), proprioception (Two-point and light touch discrimination) from patients with squamous carcinoma of oral tongue, surgically treated between July 2021 and September 2022, and stratified them based on pT stage. The pathologist was blinded to the clinical data and correlation with the sensory dysregulations was obtained using a multivariate analysis. Factors predicting overall survival (OS) and disease specific survival (DSS) were calculated using Kaplan–Meier method. Results 100 patients were followed up with a median of 13 months. Radiating pain predicted advanced disease, extranodal extension (ENE) and perineural invasion (PNI). Loss of sweet and salty taste were associated with advanced disease, Depapillation and PNI. Among early tumors, 26% had taste alterations, with loss of sweet taste significantly associated with Depapillation and PNI. Loss of light touch was significantly associated with presence of PNI, while loss of two-point discrimination was associated with larger tumors, PNI and poor grade. The OS was significantly reduced when pain scores were moderate to severe at their least within 24 h from interview and loss of light touch. Conclusion Radiating pain, sweet and salty taste dysregulation and loss of sensory discrimination have a strong correlation with PNI and impact survival.

The Role of Adjuvant Therapies in Improving Outcomes for pT1-3N0 Oral Squamous Cell Carcinoma With Tumour-Free Margins and Perineural Invasion.

Introduction The role of concomitant chemoradiation therapy (CTRT) or radiation therapy (RT) is not well defined in operated cases of oral squamous cell carcinoma (OSCC) with positive perineural spread. The purpose of the study was to determine whether the use of concurrent CTRT or RT would enhance the five-year disease-free survival of patients with positive perineural invasion (PNI). Materials and methods Data were analysed retrospectively from January 2014 to December 2023. Patients were placed into three groups: surgery only, surgery with RT, and surgery with concomitant CTRT. In all, 180 cases of pT1-3N0 and pT1-3N+ OSCC patients had tumour-free margins, of which 24 cases (13.4%) had perineural invasion. Based on treatment modalities, 45.8% of the cases underwent surgery with CTRT (group III), 33.3% opted for surgery with RT (group II), and 20.9% underwent surgery only (group I). Five-year recurrence-free survival was analysed amongthe three groups using the Kaplan-Meier model. Results There was no significant difference among the three groups in terms of recurrence (p = 0.817) or five-year survival rate (p = 0.0935). Conclusion Altogether, the data seem to indicate that radical surgical resection alone should be considered sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion. Thus, it can be concluded that the addition of concomitant CTRT or RT does not significantly increase the five-year disease-free survival of patients with OSCC with positive PNI.

Lymph Node Evolution in Eyelid and Orbit Squamous Cell Carcinomas.

To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node involvement among tumor characteristics. All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses. Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution. Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement. 4 Laryngoscope, 134:4956-4963, 2024.

Diagnostic value of the flare sign in predicting extracapsular extension in metastatic axillary lymph nodes and nodal status on breast magnetic resonance imaging.

This study aimed to evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in predicting extracapsular extension (ECE) and axillary nodal status in the axillary metastatic lymph nodes of patients with breast cancer. The preoperative MRI scans of 92 patients with breast cancer and axillary metastases who did not receive neoadjuvant treatment between January 2018 and January 2024 were retrospectively examined. The presence of an increased signal in the axillary fatty tissue surrounding the lymph node (flare sign) on T2-weighted images, irregular nodal contour (shaggy margin), axillary asymmetry (difference in the number and size of lymph nodes compared with the unaffected axilla), loss of the fatty hilum in the most suspicious lymph node, and morphological features on T1-weighted images were assessed. Each dissected axillary lymph node was examined for ECE, and the histopathological results were recorded. Axillary flare sign was significantly associated with the presence of ECE (P < 0.001), number of lymph nodes with ECE (P < 0.001), the presence of ≥4 axillary metastatic lymph nodes (P < 0.001), size of the primary tumor (P = 0.033), lymphovascular invasion in the primary tumor (P < 0.001), and presence of perineural invasion (P = 0.001). The flare sign exhibited 65.7% sensitivity, 96% specificity, 97.8% positive predictive value, 51.1% negative predictive value, and 73.9% accuracy in predicting ECE. Additionally, the receiver operating characteristic curve analysis revealed an area under the curve of 0.808 (95% confidence interval: 0.719-0.898). The flare sign has high performance in predicting ECE and axillary nodal status and is associated with primary tumor aggressiveness, indicating its potential utility in preoperative evaluation. The flare sign on breast MRI may play a crucial role in preoperative planning, surgical decision-making, and axillary status assessment by accurately predicting ECE.

The relationship between the Prognostic Nutritional Index and lymphovascular and perineural invasion of the tumor in patients diagnosed with gastric cancer, and its effect on overall survival.

A low Prognostic Nutritional Index (PNI) value, lymphovascular invasion (LVI), and perineural invasion (PeNI) have been identified as indicators of poor prognosis for many malignancies. We aimed to evaluate the relationship between PNI and LVI/PeNI, their prognostic significance, and their effect on overall survival in gastric cancer patients who underwent curative gastrectomy. A cutoff value of 39.8 was taken for the PNI, and PNI < 39.8 was defined as moderate to severe malnutrition. Patients were grouped as PNI-low (PNI < 39.8) and PNI-high (PNI ≥ 39.8). Paraffin-embedded tissue sections of surgical specimens were used to evaluate PeNI as defined by previously reported criteria. The study included 270 patients with ages ranging from 23 to 90 years. The mean PNI was calculated as 39.8 ± 6.35. PeNI was detected in 232 patients (85.93%), and LVI was identified in 248 patients (91.85%). It was observed that the PNI value of patients with an expired status in the PNI < 39.8 group was lower compared to those who survived, and in patients with PNI > 39.8, those without PeNI had better survival. The presence of PeNI in patients with PNI > 39.8 increased the mortality risk by 2.088 units, while in patients with PNI > 39.8, it was found that those without LVI had better survival, and the presence of LVI increased the mortality risk by 3.171 units. Mortality developed in 166 patients (61.48%) during the five-year follow-up period. The five-year overall survival was found to be 31.02 ± 21.73 months. In patients with gastric cancer, the PNI, LVI, and PeNI are independent prognostic factors for overall survival in postoperative patients. A low PNI score is an inherently poor prognostic factor. In patients with a high PNI score, the presence of positive LVI and PeNI negatively impacts survival. We found that in patients with a low PNI, the rates of PeNI and LVI are higher compared to those with a high PNI, and this significantly affects mortality.

Predictors of extra nodal extension in oral squamous cell carcinoma: A retrospective analysis

ABSTRACT Background: Extranodal extension (ENE) has emerged as the strongest predictor of recurrence in oral squamous cell carcinoma (OSCC) and the only operator-independent predictor of treatment intensification in the form of adjuvant chemoradiation. Objectives: The primary objective was to identify various clinical and pathological predictors of pathological ENE (pENE) in surgically resected OSCC, and the secondary objective was to determine accuracy of clinical ENE (cENE) in predicting pathological ENE (pENE). Materials and Methods: In this retrospective analysis, we included all biopsy proven patients with OSCC who underwent surgery with appropriate neck dissection from April 2018 - December 2022 at the Department of Otolaryngology-Head-and-Neck Surgery, All India Institute of Medical Sciences Rishikesh, India. Tumors were staged according to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition tumor, node and metastasis (TNM) classification. Clinical and pathological variables were subjected to univariate and multivariate analyses. Results: We enrolled 299 patients in this study. Pathological bone invasion (BI), presence of perineural invasion (PNI), total number of positive lymph nodes, and lymph node ratio (LNR) were found to be independent predictors of pENE in both univariate and multivariate analyses. Post hoc analysis showed that ≥ 5 positive lymph nodes and LNR of ≥ 0.1 were significantly associated with pENE. Clinical ENE (cENE) exhibited a high specificity (92.9%) and negative predictive value (89.4%) for pENE. Conclusion: Clinical tumor characteristics are poor predictors of pENE. BI, PNI, and pathological nodal parameters, namely, total number of positive nodes and lymph node ratio, are the major predictors of pENE.

The surgical outcome of standard lobectomy versus sleeve lobectomy in patients with non-small cell lung cancer: propensity score matching.

The goal of this study was to compare the patients who underwent standard or sleeve lobectomy for non-small cell lung cancer in terms of postoperative outcomes, prognostic factors and overall survival. Between January 2002 and January 2020, the patients with squamous cell carcinoma or adenocarcinoma who underwent standard lobectomy or sleeve lobectomy by thoracotomy in our clinic were analysed retrospectively. Standard and sleeve groups were compared after propensity score matching in terms of age, comorbidity, T status, N status and pathological stage. Primary outcomes were morbidity and mortality; the secondary outcome was overall survival. The study included 476 patients, and sleeve lobectomy was performed in 196 (41.1%) patients. Multivariable analysis revealed that age over 61 years (P = 0.003 and P = 0.005, respectively), forced expiratory volume in 1 s (FEV1) below 84% (P = 0.013 and P = 0.205, respectively) and the presence of perineural invasion (P = 0.052 and P = 0.001, respectively) were poor prognostic factors in the standard lobectomy and the sleeve groups. The propensity matching analysis included 276 patients (138 sleeve lobectomy and 138 standard lobectomy). Complications occurred in 96 (69.6%) and 92 (66.7%) patients in the standard and sleeve groups, respectively (P = 0.605). Three (2.2%) patients in the standard group and 5 (3.6%) patients in the sleeve group died within 90 days postoperatively (P = 0.723). Bronchial sleeve lobectomy is a safe procedure that can be applied in oncologically suitable cases without causing higher mortality than a standard lobectomy.

Promotion of perineural invasion of cholangiocarcinoma by Schwann cells via nerve growth factor.

Cholangiocarcinoma (CCA), a highly lethal tumor of the hepatobiliary system originating from bile duct epithelium, can be divided into the intrahepatic, hilar, and extrahepatic types. Due to its insidious onset and atypical early clinical symptoms, the overall prognosis is poor. One of the important factors contributing to the poor prognosis of CCA is the occurrence of perineural invasion (PNI), but the specific mechanisms regarding how it contributes to the occurrence of PNI are still unclear. The main purpose of this study is to explore the molecular mechanism leading to the occurrence of PNI and provide new ideas for clinical treatment. CCA cell lines and Schwann cells (SCs) were stimulated to observe the changes in cell behavior. SCs cocultured with tumor supernatant and SCs cultured in normal medium were subjected to transcriptome sequencing to screen the significantly upregulated genes. Following this, the two types of tumor cells were cultured with SC supernatant, and the changes in behavior of the tumor cells were observed. Nonobese diabetic-severe combined immunodeficiency disease (NOD-SCID) mice were injected with cell suspension supplemented with nerve growth factor (NGF) via the sciatic nerve. Four weeks later, the mice were euthanized and the tumor sections were removed and stained. Nerve invasion by tumor cells was common in CCA tissues. SCs were observed in tumor tissues, and the number of SCs in tumor tissues and the degree of PNI were much higher than were those in normal tissues or tissues without PNI. The overall survival time was shorter in patients with CCA with PNI than in patients without PNI. SCs were enriched in CCA tissues, indicating the presence of PNI and associated with poor prognosis in CCA patients. CCA was found to promote NGF secretion from SCs in vitro. After the addition of exogenous NGF in CCA cell culture medium, the proliferation activity and migration ability of CCA cells were significantly increased, suggesting that SCs can promote the proliferation and migration of CCA through the secretion of NGF. NGF, in turn, was observed to promote epithelial-mesenchymal transition in CCA through tropomyosin receptor kinase A (TrkA), thus promoting its progression. Tumor growth in mice shows that NGF can promote PNI in CCA. In CCA, tumor cells can promote the secretion of NGF by SCs, which promotes the progression of CCA and PNI by binding to its high-affinity receptor TrkA, leading to poor prognosis.

Association of CDX2 expression with clinical, pathologic, and molecular features in MSI-H colorectal cancer.

e15583 Background: Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and are seen in 15% of early stage and 5% of metastatic disease. CRC with the MMR-D/MSI-H phenotype carries unique characteristics that are associated with increase mutational burden. Specifically, loss of CDX2 expression is associated with aggressive carcinomas and correlates with worse disease-free survival in the general population. However, the impact of loss of CDX2 expression in MMR-D/MSI-H phenotype is not well known. In this study, we investigated the association of loss of CDX2 expression with clinical and pathological outcomes. Methods: We retrospectively reviewed 543 patients who were diagnosed with colorectal cancer with pathological findings for the presence of MMR-D/MSI-H phenotype, and who had been seen at UPMC Hillman Cancer Center from 2013-2020. CDX2 expression was evaluated across all patients for the association with various molecular, pathological features and survival. In our investigations of association with loss of CDX2, coded as a binary variable in an H score, we used Mann-Whitney or two-sample (Welch’s) t-test for continuous variables, and Chi-square or Fisher’s exact tests for categorical variables. For RFS and OS, we compared H score groups with log-rank tests at two-sided alpha = 0.05 and plotted respective Kaplan-Meier curves. Results: A total of 99 patients were identified with adequate tissue sample to assess for CDX2 expression and with consistent clinical follow-up from date of diagnosis to present. When examining loss of CDX2 expression and association with pathological factors, we observed a significant association with a higher T4 stage (43% vs 14%; p = 0.008), and high grade tumor (86% vs 22%; p = 1.086 x 10-8 ) as well as presence of PNI (peri-neural invasion) (36% vs 17%; p = 0.030). There was no association observed between CDX2 expression and N stage or location of tumor. When examining loss of CDX2 expression and association with molecular factors, we observed that patients with Lynch syndrome were more likely to preserve CDX2 expression (0% vs 27%; p = 0.001) while patients with BRAF mutation were more likely to present with loss of CDX2 expression. Finally, patients with loss of CDX2 expression had numerically lower median survival (8.2 years vs. 9.3 years) though this did not reach statistical significance (p = 0.120). Conclusions: Overall, loss of CDX2 expression correlates with worse pathological features as it was significantly seen in patients with a diagnosis of CRC at a higher T stage, grade, presence of PNI and presence of BRAF mutation. Although no significant association was observed in terms of survival outcomes due to likely insufficient power, a notable separation of survival curves was noted, which indicates overall lower survival.

Exploring the neutrophil-to-lymphocyte ratio as a prognostic biomarker in triple-negative breast cancer

Triple-negative breast cancer is a subtype characterized by the absence of estrogen receptor, progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 receptors, limiting treatment options primarily to chemotherapy due to lack of targeted therapies typically used for other breast cancer types, hence necessitating research for improved therapeutic strategies and outcomes. The neutrophil and lymphocyte percentages, absolute counts, and the ratio of neutrophils to lymphocytes were evaluated in peripheral blood of 81 patients with triple-negative breast cancer (TNBC) and 25 healthy controls. This study observed trend of high neutrophil percentage was observed in patients with positive lymph node status as compared to negative lymph node status. Significant high absolute neutrophil count was observed in patients with positive LN status, High BR score and presence of metastasis. A trend of high neutrophil to lymphocyte ratio was observed in patients with presence of perineural invasion, presence of necrosis, and patients with presence of metastasis.

Clinical and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.

Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp. A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately. Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases. In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.

Shedding light on the shadows: oxidative stress and its pivotal role in prostate cancer progression.

Data on oxidative protein damage, total antioxidant capacity (TAC) and lipid peroxidation in progression of prostate cancer remain elusive. So far, the influence of the presence of perineural invasion on the level of oxidative stress has not been described. Additionally, there is limited data on the level of oxidative stress in patients' urine. We compared the levels of oxidative stress markers in serum and urine in 50 patients with prostate cancer depending on the tumor stage and histological grade, the Gleason score, and the presence of perineural invasion. We found a significantly de-creased level of serum thiol groups and TAC in participants with prostate cancer. Similarly, serum Amadori products and malondialdehyde (MDA) were higher in patients than in healthy men. There was a significantly decrease in TAC and a significantly increased MDA in the urine of prostate cancer patients. As the stage of cancer increased, a decrease in the thiol group concentration and TAC as well as an increase in the concentration of lipid peroxidation products in the serum was observed. The serum level of advanced oxidation protein products (AOPP) increased in the group with Gleason scores greater than 7. Furthermore, serum thiol groups and TAC were reduced in the group with Gleason >7 as compared to Gleason <7. The presence of perineural invasion significantly reduced serum and urinary TAC and increased urinary AOPP concentration. These results indicate a significant role for oxidative damage in prostate carcinogenesis and its progression. Characterizing oxidative and nitrosative damage to proteins may be useful in designing targeted therapies for prostate cancer patients.

CLINICO-PATHOLOGICAL ANALYSIS OF GASTRIC CANCER – A SINGLE INSTITUTION EXPERIENCE

Introduction: Gastric cancer (GC) is one of the leading causes of cancer related morbidity and mortality. Morphologically, GC is a heterogeneous neoplasm consisting of several histological types. Majority of the patients are diagnosed in an advance stage of the disease. Conventional surgical and systemic treatment has demonstrated limited achievement. Evolution in personalized therapy is a main factor to improve the outcome, but for a successful application, a careful stratification of patients is required. Aim: The purpose of the present paper was to analyze the mandatory clinical and pathological characteristics of patients with GC. Material and methods: A total 74 patients who have undergone total or partial gastric resection, endoscopic and laparoscopic biopsy due to GC were included. Results: The average age of the patients was 69,6 years, with a male predominance in all age groups. Most frequent histological type was intestinal type, according to Lauren and tubular type, according to WHO classifications. 82,3% (p&lt;0,05) of GC located in cardia were diagnosed in males. 37/42 tubular, papillary and mucinous types by WHO classification were classified as intestinal type by Lauren. All signet ring cell and poorly cohesive adenocarcinomas by WHO classification were accordingly assigned as diffuse type by Lauren. 52,2% of the tubular/intestinal type of tumors were graded as G1 or G2, and 93,1% of signet ring and poorly cohesive/diffuse type GC were graded as G3. Significant correlations were observed between perineural invasion and histological type by Lauren (p&lt;0,043), degree of differentiation (p&lt;0,04) and lymphovascular invasion (p&lt;0,000); between а degree of inflammatory reaction and М status (p&lt;0,022). Conclusion: Precise histological typification of GC is a key to better stratification of the patients. Certain histological types are associated with aggressive tumor behavior, as we found diffuse type to correlate with poor differentiation and presence of perineural invasion. Degree of inflammatory reaction may be an independent indicator of the presence of distant metastases.

Oncologic Outcomes of Salvage Surgery in Recurrent Oral Tongue Squamous Cell Carcinoma.

This study aimed to determine the oncologic outcomes and identify prognostic factors in patients undergoing salvage glossectomy for recurrent oral tongue squamous cell carcinoma (OTSCC). A retrospective chart review was conducted encompassing all patients who underwent salvage oral glossectomy out of 259 individuals undergoing oral glossectomy at a tertiary academic center. Inclusion criteria comprised patients who met the following conditions: 1) biopsy-proven oral tongue recurrence, 2) salvage glossectomy performed with curative intent, 3) availability of imaging records, and 4) comprehensive documentation. Cases involving base of tongue tumors and second primaries were excluded from the analysis. Categorical data were expressed as proportions, and continuous data as medians/quartiles. Univariate analysis used Fisher's exact test for categorical variables and Student's t-test for continuous ones. Survival analysis employed Kaplan-Meier estimates and the log-rank test. High-risk histopathological risk factors were significantly more common with recurrence compared to initial presentation. The mean locoregional disease-free interval was 35 months.Kaplan-Meier estimates for one- and three-year disease-free survival (DFS) were 62.7% and 33.4%, while disease-specific survival (DSS) rates were 73% and 38.9%, respectively.Recurrent T-stage was a predictor for DFS, while margin status was a strong predictor for both LR control (p = 0.024) and DSS (p = 0.030), as was perineural invasion (p = 0.001 and p = 0.030). Alcohol use was associated with worse overall survival (p = 0.024).In contrast to other reports, nodal status was not a predictor in this series. Upon recurrence, histopathological analysis unveils detrimental changes in tumor biology, which significantly influence disease control. Notably, consistent with findings from other studies, factors, such as recurrent T-stage, presence of perineural invasion, and, most importantly, margin status, play pivotal roles in determining oncologic outcomes. Consequently, the imperative for aggressive salvage surgery becomes evident in achieving sufficient disease control. This underscores the necessity for proactive management strategies aimed at addressing these factors to enhance patient outcomes.

Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study.

The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.

Clinicopathological factors predict residual lymph node metastasis in locally advanced rectal cancer with ypT0-2 after neoadjuvant chemoradiotherapy

PurposeResidual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT).MethodsWe retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50–50.6 Gy for the planning gross tumor volume and 41.8–45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC).ResultsAfter surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610–0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness.ConclusionThe nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.

Abstract 5525: Tissue-resident cytotoxic T cell infiltration predicts metachronous colorectal cancer metastasis

Abstract Background: Identifying patients at high risk for metachronous colorectal cancer metastasis is essential for improving prognosis. The balance between host immune regulation and tumor immune evasion ultimately permits or prevents cancer progression. Lymphocytic infiltration in colorectal cancer can predict long-term clinical outcomes. However, these lymphocytes' origin, subtype and function have yet to be adequately explored. We investigated the association between the development of metastasis and CD8+T cells expressing the integrin protein CD103, a marker of tissue-resident memory T cells. Methods: In this retrospective, case-control matched study, we conducted multiplex immunofluorescence staining of tumor samples from 124 patients with colorectal cancer. Tissue microarrays containing representative cores of the central tumor, invasive margin, and adjacent normal tissue were immunostained for CD3, CD8, CD103, pSMAD3, and cytokeratin, using tyramide signal amplification. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kruskal-Wallis one-way analysis of variance with subsequent Dunn’s test for pair-wise comparisons was performed using the Bonferroni method of multiple-comparison correction. Results: Central tumor and invasive margin CD3+ densities were associated with synchronous metastasis. Compared to non-metastatic patients, those who went on to develop metachronous metastasis (n=42) had a low proportion of intra-epithelial CD8+CD103+ T cells at the central tumor (non-metastatic: 32.8%, IQR 15.0-42.7%; metachronous metastasis: 12.9%, IQR 2.08-28.4%; P = 0.013). Similarly, patients with metachronous metastasis had a low proportion of stromal CD8+CD103+ T cells at the invasive margin (non-metastatic: 3.51%, IQR 1.83-6.55%; metachronous metastasis: 1.75%, IQR 0.62-3.72%; P = 0.019). On multivariate Cox regression of histological features, amongst patients with metastasis, significant overall survival prognostic markers included a low proportional CD8+CD103+ T cell infiltration (HR 2.41, 95%CI 1.16-5.01, P = 0.019), mucinous features (HR 4.28, 95%CI 1.98-9.24, P &amp;lt; 0.001), and the presence of perineural invasion (HR 2.75, 95%CI 1.28-5.89, P &amp;lt; 0.001). Conclusion: CD8+CD103+ lymphocytes may protect from the development of colorectal metastasis. Proportional CD8+CD103+ T cell infiltration is a promising prognostic marker in colorectal adenocarcinoma for the development of metachronous metastasis, and, amongst patients with metastasis, it is a prognostic marker of overall survival. Citation Format: Ryan Cohen, Tracey Lee-Pullen, Timothy Miller, Shadi Pirasteh, Cameron Platell, Katie Meehan, Kathy Fuller, Melanie McCoy. Tissue-resident cytotoxic T cell infiltration predicts metachronous colorectal cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5525.