Perineural Invasion Is a Prognostic but not a Predictive Factor in Nonmetastatic Colon Cancer.

Published on Oct 1, 2019in Diseases of The Colon & Rectum3.991
· DOI :10.1097/DCR.0000000000001450
Lieve G. J. Leijssen6
Estimated H-index: 6
(Harvard University),
Anne M. Dinaux8
Estimated H-index: 8
(Harvard University)
+ 4 AuthorsDavid H. Berger75
Estimated H-index: 75
(Harvard University)
Sources
Abstract
BACKGROUND: Perineural invasion is associated with adverse oncological outcomes in colorectal cancer. However, data regarding the prognostic and predictive impact in colon cancer are scarce. OBJECTIVE: This study aims to clarify the role of perineural invasion in patients with nonmetastatic colon cancer. DESIGN: This study is a retrospective review of a prospectively maintained database. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with stage I to III colon cancer who underwent elective surgery at our tertiary center between 2004 and 2015 (n = 1145) were included. MEAN OUTCOME MEASURES: The primary long-term outcomes include disease-free survival, disease-specific survival, and overall survival. Differences were determined by multivariate Cox regression models adjusted for stage and potential confounders. RESULTS: Perineural invasion was identified in 215 patients (18.8%) and associated with emergency procedures, male sex, and advanced disease. Histopathological features including lymphatic and extramural vascular invasion, poor differentiation, and infiltrating tumor borders were correlated with perineural invasion. Compared with patients with perineural invasion-negative tumors, patients who had perineural invasion-positive tumors had worse disease-free, overall, and disease-specific survival (all p < 0.001). Moreover, patients with perineural invasion-positive node-negative disease had worse overall survival than patients with perineural invasion-negative node-positive disease (p < 0.001). After adjustment, perineural invasion remained significantly associated with worse disease-free survival (HR, 1.45; 95% CI, 1.03-2.03; p = 0.033), worse overall survival (HR, 1.75; 95% CI, 1.33-2.31; p < 0.001), and worse disease-specific survival (HR, 1.52; 95% CI, 1.00-2.30; p = 0.048). However, we did not find a significant predictive response with adjuvant chemotherapy in perineural invasion-positive node-negative tumors (HR, 2.10; 95% CI, 0.80-5.51; p = 0.122). The predictive value was only demonstrated in stage III disease with a significant impaired overall survival in patients with perineural invasion-positive tumors who did not receive adjuvant therapy (HR, 0.23; 95% CI, 0.13-0.40; p < 0.001). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Our study confirms the prognostic value of perineural invasion in stage I to II and III colon cancer. However, patients with node-negative disease and perineural invasion did not significantly benefit from adjuvant therapy. More information regarding postoperative treatment in node-negative perineural invasion-positive colon cancer is required. See Video Abstract at http://links.lww.com/DCR/A988. LA INVASION PERINEURAL COMO FACTOR PRONOSTICO NO PREDICTIVO EN EL CANCER DE COLON NO METASTASICO: La invasion perineural se encuentra asociada a resultados oncologicos adversos en casos de cancer colorrectal. Sin embargo, los datos sobre el impacto pronostico y predictivo en caso de cancer de colon son pocos. OBJETIVO: Definir el papel de la invasion perineural en pacientes con cancer de colon no metastasico. DISENO:: Revision retrospectiva de una base de datos alimentada prospectivamente. AJUSTES: Centro hospitalario de atencion terciaria. PACIENTES: Todos aquellos portadores de un cancer de colon estadio I-III que se sometieron a cirugia electiva en nuestro centro entre 2004-2015 (n = 1145). PRINCIPALES RESULTADOS: Los resultados a largo plazo incluyeron la supervivencia sin enfermedad, la supervivencia especifica de la enfermedad y la supervivencia general. Las diferencias se determinaron mediante modelos de regresion multivariantes de Cox, ajustados para el control de factores de confusion durante el analisis por estratificacion. RESULTADOS: La invasion perineural fue identificada en 215 pacientes (18.8%) y se la asocio con procedimientos de emergencia, al genero masculino y a la enfermedad avanzada. Las caracteristicas histopatologicas que incluyeron la invasion vascular linfatica y extramural, la diferenciacion deficiente y los bordes tumorales infiltrantes se correlacionaron con la invasion perineural. Comparativamente con los tumores sin invasion perineural, los pacientes positivos a la invasion perineural tuvieron una peor supervivencia general, libre y especifica de la enfermedad (todos p < 0.001). Asimismo, aquellos pacientes con invasion-perineural con ganglios negativos tuvieron una supervivencia global mucho peor que aquellos pacientes con ganglios positivos e invasion perineural negativa (p < 0.001). Despues del ajuste, la invasion perineural se asocio significativamente con una peor supervivencia sin la enfermedad (HR, 1.45; IC 95%, 1.03-2.03; p = 0.033), supervivencia general (HR, 1.75; IC 95%, 1.33-2.31; p <0.001), asi como con una peor supervivencia especifica de la enfermedad (HR, 1.52; IC 95%, 1.00-2.30; p = 0.048). Sin embargo, no encontramos una respuesta predictiva significativa con quimioterapia adyuvante en los tumores acompanados de invasion-perineural con ganglios negativos (HR, 2.10; IC del 95%, 0.80-5.51; p = 0.122). El valor predictivo solo fue demostrado en aquellos casos de estadio III con un deterioro significativo de la supervivencia global en pacientes con tumores perineurales positivos a la invasion y que no recibieron tratamiento adyuvante (HR, 0.23; IC 95%, 0.13-0.40; p < 0.001). LIMITACIONES: Diseno retrospectivo. CONCLUSION:: Nuestros resultados confirman el valor pronostico de la invasion perineural en el cancer de colon estadios I-II y III. Sin embargo, los pacientes con enfermedad ganglionar negativa e invasion perineural no se beneficiaron significativamente de la terapia adyuvante. Se requiere mas informacion sobre el tratamiento postoperatorio en el cancer de colon positivo para la invasion perineural con ganglios negativos. Vea el Resumen del video en http://links.lww.com/DCR/A988.
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Background Perineural invasion (PNI) in colon cancer (CC) has been associated with poorer prognosis even in stage II disease (T3–4 N0 M0). The aim of this study is to analyze prognostic histopathologic factors in stage II colon cancer in patients treated with curative surgery as established in National Comprehensive Cancer Network guidelines.
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#1Abdulrahman Muaod Alotaibi (UOU: University of Ulsan)H-Index: 2
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Background The presence of perineural invasion (PNI) in colorectal cancer (CRC) indicates a more aggressive phenotype, resulting in a poor prognosis. The aims of this study were to evaluate the oncologic outcome of PNI+ tumors and to investigate whether PNI status affects patient survival.
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Perineural invasion (PNI) is a possible route for metastatic spread in various cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis, but systematic analyses are lacking. This study systematically reviews the frequency and impact of PNI in CRC. A literature search was performed using PubMed database from inception to January 1, 2014. Data were analyzed using Review Manager 5.3. A quality assessment was performed on the basis of modified REMARK criteria. Endpoints were ...
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Background The role of adjuvant chemotherapy in patients with stage II colon cancer is unclear. Current guidelines recommend adjuvant chemotherapy for high-risk patients, although the benefit demonstrated to date is small. Our study examined if adjuvant chemotherapy is associated with improved cancer-specific survival in high-risk patients with stage II colon cancer. Methods A retrospective review was performed on patients with stage II (T3-4N0M0) colon cancer in a multi-institutional database f...
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Objective The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM).
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Perineural invasion (PN) in colorectal cancer (CRC) is a site-specific prognostic marker, as mentioned by the AJCC Cancer Staging Manual, but it remains to be clearly defined. We aimed to identify an optimal characterization of PN as a component of cancer staging. On the basis of the anatomic featur
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Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to gen...
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BACKGROUND: The authors' purpose was to explore the incidence and prognostic significance of perineural invasion (PNI) in pT3N0 rectal cancer. METHODS: Pathologic materials from resected specimens of 173 patients with pT3N0 rectal cancer were retrospectively collected. PNI-positivity was categorized into 2 groups: surrounding the nerve sheath (SS-PNI) and invading through the nerve sheath (TS-PNI). The rate of PNI-positivity was compared with PNI as initially recorded in the original reports. Pa...
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Introduction Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and through intra and extrapancreatic nerves, even during the early stages of the disease, a phenomenon called perineural invasion (PNI). Thus, we sought to determine the effects of the simultaneous expression of soluble forms of GAS1 and PTEN (tGAS1 and PTEN-L) inhibiting tumor growth and invasiveness. Materials and Methods We employed a lentiviral system to simultaneously express tGAS1 and PTEN-L; in order to...
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