The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy

Context.— Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. Objective.— To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. Design.— We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. Results.— PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1–3), pT (GG1–2/GG1–3/GG2/GG3), surgical margin status (GG1–3/GG3/GG5), or tumor volume (GG1–2/GG1–3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1–2 versus 3–6/1–3 versus 4–6/1–4 versus 5–6), RP GG (1–3 versus 4–6/1–4 versus 5–6), pT (1–2 versus 3–6/1–3 versus 4–6), pN (1–3 versus 4–6), or tumor volume (1–2 versus 3–6/1–4 versus 5–6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1–2/GG1–3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Conclusions.— Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1–3 cancer.

Difference in Clinical Presentation and Their Significance in Oral Squamous Cell Carcinoma – a Retrospective Analysis

Oral squamous cell carcinoma(OSCC) involving tongue and buccoalveolar complex(BAC) behaves differently. Clinical features of the two subsites and their influence on pathological factors remain least analysed. Patients are divided into two groups i.e, tongue cancer and BAC cancer group, and various clinical parameters were compared. Among 474 patients 232 had tongue cancer and 242 had BAC cancer. 30% of patients with OSCC were asymptomatic at presentation except for the ulcer. Compared to tongue cancers, lesions confined to BAC presents at an advanced stage(p=0.006). Multivariate analysis showed that dysphagia in tongue cancer(p=0.020) and external swelling or lesion in BAC cancers(p=0.002) were significant predictors of an advanced stage of disease. On histopathology perineural invasion was significantly associated tongue(p=0.008) and BAC cancers(P=0.015). Among tongue cancers, those with pain and referred otalgia had a statistically significantly high depth of invasion(DOI), compared to those without pain (DOI – no pain 6.9mm, pain 9.9mm and referred otalgia 11.4mm). There is a delay in clinical presentation of OSCC. Among tongue cancers, clinical history of pain was significantly associated with depth of invasion and perineural invasion, the significance of which needs to be prospectively analysed. Clinical history in OSCC can be used as predicting factors for various pathological characters, which is subsite specific.

Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing

We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r = − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.

Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center

The aims of this study were to assess the prevalence of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) and its prognostic role in locoregional recurrence (LRR) and cancer-specific survival (CSS). We performed a retrospective analysis of 223 consecutive stage IB–IIIC surgically treated VSCCs at S. Anna Hospital, University of Turin, from 2000 to 2019. We identified 133/223 (59.6%) patients with PNI-positive VSCCs. PNI was associated with aggressive biological features (i.e., advanced FIGO stage, larger tumor diameter, greater depth of invasion, a higher number of metastatic lymph nodes, and lymphovascular invasion) and shorter 5-year CSS (78% vs. 90%, log-rank p = 0.02) compared with PNI-negative VSCCs. Multivariate analysis showed that PNI (HR 2.99 CI 95% 1.17–7.63; p = 0.02) and the presence of tumor cells on pathological surgical margins (HR 3.13 CI 95% 1.37–7.13; p = 0.007) are independent prognostic factors for CSS. PNI does not appear to be related to LRR, but is an independent prognostic factor for worse survival outcomes. Future studies are necessary to explore the possible value of PNI in tailoring the choice of adjuvant treatment.

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram

BackgroundPerineural invasion (PNI) is associated with a poor prognosis for cervical cancer and influences surgical strategies. However, a preoperative evaluation that can determine PNI in cervical cancer patients is lacking.MethodsAfter 1:1 propensity score matching, 162 cervical cancer patients with PNI and 162 cervical cancer patients without PNI were included in the training set. Forty-nine eligible patients were enrolled in the validation set. The PNI-positive and PNI-negative groups were compared. Multivariate logistic regression was performed to build the PNI prediction nomogram.ResultsAge [odds ratio (OR), 1.028; 95% confidence interval (CI), 0.999–1.058], adenocarcinoma (OR, 1.169; 95% CI, 0.675–2.028), tumor size (OR, 1.216; 95% CI, 0.927–1.607), neoadjuvant chemotherapy (OR, 0.544; 95% CI, 0.269–1.083), lymph node enlargement (OR, 1.953; 95% CI, 1.086–3.550), deep stromal invasion (OR, 1.639; 95% CI, 0.977–2.742), and full-layer invasion (OR, 5.119; 95% CI, 2.788–9.799) were integrated in the PNI prediction nomogram based on multivariate logistic regression. The PNI prediction nomogram exhibited satisfactory performance, with areas under the curve of 0.763 (95% CI, 0.712–0.815) for the training set and 0.860 (95% CI, 0.758–0.961) for the validation set. Moreover, after reviewing the pathological slides of patients in the validation set, four patients initially diagnosed as PNI-negative were recognized as PNI-positive. All these four patients with false-negative PNI were correctly predicted to be PNI-positive (predicted p > 0.5) by the nomogram, which improved the PNI detection rate.ConclusionThe nomogram has potential to assist clinicians when evaluating the PNI status, reduce misdiagnosis, and optimize surgical strategies for patients with cervical cancer.

Perineural Invasion is an Indication of Adjuvant Chemotherapy in Node Negative Colorectal cancer

Review question / Objective: Perineural invasion (PNI) is a possible route for metastatic spread in various cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis. For patients with lymph node positive colorectal cancer, a number of large-scale RCT studies have confirmed that they can benefit from chemotherapy, but there are still many controversies about whether colorectal patients with negative lymph nodes need adjuvant chemotherapy. At present, there is a general consensus that patients with stage II colorectal cancer who have risk factors such as PNI+ need chemotherapy. However, there are many recent literatures that show that patients with stage II colorectal cancer with nerve invasion risk factors can not prolong the OS and DFS of patients. At the same time, chemotherapy increases the toxicity, economic and mental burden of patients. Therefore, we hope to write this review to summarize the current research findings and provide some clinical guidance on whether patients with lymph node negative colon cancer who have perineural invasion should receive chemotherapy. Condition being studied: Patients with high-risk such as PNI+ stage II colon cancer (CC) are recommended to undergo adjuvant chemotherapy (ACT). However, whether such patients can benefit from ACT remains unclear. And recently studies shown that, ACT had no significant benefit among patients with PNI.

Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio and its variation pre and post-operatively (delta NLR) in overall survival after pancreatectomy for pancreatic ductal adenocarcinoma at a single centre and to identify factors associated with overall survival.Methods: A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between evaluated factors and overall survival were analyzed using a log-rank test and Cox proportional hazard regression model.Results: Overall, 242 patients underwent complete pancreatic resection for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% CI: 19.5-29) and survival rates at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. NLR and delta NLR were not significantly associated with survival (HR=1.14, 95%CI: 0.77-1.68, p=0.5). Lymph node ratio was significantly associated (HR=1.66, 95%CI: 1.21-2.26, p=0.001) in the bivariate analysis. In multivariable analysis the only factors that were significantly associated with survival were perineural invasion (HR=1.94, 95%CI: 1.21-3.14, p=0.006), surgical margin (HR=1.83, 95%CI: 1.10-3.02, p=0.019), tumor size (HR=1.01, 95%CI: 1.003-1.027, p=0.16), postoperative CA 19-9 level (HR=1.001, p<0.001), and completion of adjuvant treatment (HR=0.53, 95%CI: 0.35-0.8, p=0.002).Conclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.