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Przeglad Gastroenterologiczny 2024Pancreaticoduodenectomy is a major procedure. Delayed gastric emptying (DGE) is a frequent postoperative complication that is attributed to several factors.
Association between perineural infiltrations and delayed gastric emptying after Whipple procedure for periampullary tumours, and the relationship with other clinicopathological factors and overall survival.
INTRODUCTION
Pancreaticoduodenectomy is a major procedure. Delayed gastric emptying (DGE) is a frequent postoperative complication that is attributed to several factors.
AIM
To investigate the probable association between perineural infiltrations and DGE, and the effects on overall survival.
MATERIAL AND METHODS
A total of 123 patients who underwent pancreaticoduodenectomy were enrolled in the study. Factors like the presence of perineural infiltrations and post-operative DGE along with age, gender, presence of postoperative fistula, and grade of fistula and postoperative haemorrhage were analysed, and survival analyses were conducted.
RESULTS
The presence of perineural infiltrations is statistically associated with DGE occurrence ( = 0.01). Moreover, the occurrence of DGE is statistically associated with male gender ( = 0.001), worse grade of postoperative fistula ( < 0.01), and the presence of postoperative haemorrhage ( = 0.03). There was no statistical association between the presence of perineural infiltrations and the other factors. Cox regression and Kaplan-Meier survival analyses showed that increased overall survival is associated with low age ( = 0.018 and = 0.028, respectively), absence of perineural infiltrations ( = 0.005 and = 0.003, respectively), better grade of postoperative fistula ( < 0.001), and absence of postoperative haemorrhage ( < 0.001). Multivariate analysis showed that independent prognostic factors for survival prognosis are perineural infiltrations, age, the presence of postoperative pancreatic fistula, and the presence of postoperative haemorrhage.
CONCLUSIONS
This is the first study that proves a statistically significant association between the presence of perineural infiltrations and the occurrence of DGE. Moreover, perineural infiltrations are an important independent prognostic factor for overall survival, along with other clinical factors.
PubMed: 38571537
DOI: 10.5114/pg.2023.129464 -
Frontiers in Genetics 2023High nerve density in tumors and metastasis via nerves (perineural invasion-PNI) have been reported extensively in solid tumors throughout the body including...
High nerve density in tumors and metastasis via nerves (perineural invasion-PNI) have been reported extensively in solid tumors throughout the body including pancreatic, head and neck, gastric, prostate, breast, and colorectal cancers. Ablation of tumor nerves results in improved disease outcomes, suggesting that blocking nerve-tumor communication could be a novel treatment strategy. However, the molecular mechanisms underlying this remain poorly understood. Thus, the aim here was to identify molecular pathways underlying nerve-tumor crosstalk and to determine common molecular features between PNI-associated cancers. Analysis of head and neck (HNSCC), pancreatic, and gastric (STAD) cancer Gene Expression Omnibus datasets was used to identify differentially expressed genes (DEGs). This revealed extracellular matrix components as highly dysregulated. To enrich for pathways associated with PNI, genes previously correlated with PNI in STAD and in 2 HNSCC studies where tumor samples were segregated by PNI status were analyzed. Neurodevelopmental genes were found to be enriched with PNI. In datasets where tumor samples were not segregated by PNI, neurodevelopmental pathways accounted for 12%-16% of the DEGs. Further dysregulation of axon guidance genes was common to all cancers analyzed. By examining paralog genes, a clear pattern emerged where at least one family member from several axon guidance pathways was affected in all cancers examined. Overall 17 different axon guidance gene families were disrupted, including the ephrin-Eph, semaphorin-neuropilin/plexin, and slit-robo pathways. These findings were validated using The Cancer Genome Atlas and cross-referenced to other cancers with a high incidence of PNI including colon, cholangiocarcinoma, prostate, and breast cancers. Survival analysis revealed that the expression levels of neurodevelopmental gene families impacted disease survival. These data highlight the importance of the tumor as a source of signals for neural tropism and neural plasticity as a common feature of cancer. The analysis supports the hypothesis that dysregulation of neurodevelopmental programs is a common feature associated with PNI. Furthermore, the data suggested that different cancers may have evolved to employ alternative genetic strategies to disrupt the same pathways Overall, these findings provide potential druggable targets for novel therapies of cancer management and provide multi-cancer molecular biomarkers.
PubMed: 37719704
DOI: 10.3389/fgene.2023.1181775 -
Cancer Medicine Dec 2012Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in...
Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in patients with resected pancreatic cancer. We conducted a retrospective study in 544 cases of resected pancreatic adenocarcinoma seen at the University of Texas MD Anderson Cancer Center during 1996-2011. Information on tumor characteristics, diabetes history, and survival time was collected by personal interview and medical record review. Patients with diabetes before or at the time of the pancreatic cancer diagnosis were considered diabetes only. Pearson χ(2) test was used to compare categorical variables in diabetic and nondiabetic groups. Kaplan-Meier plot, log-rank test, and Cox proportional regression models were applied in survival analysis. The prevalence of diabetes and perineural invasion was 26.5% and 86.9%, respectively, in this study population. Patients with diabetes had a significantly higher prevalence of perineural invasion (92.4%) than those without diabetes (85%) (P = 0.025, χ(2) test). Diabetes was not associated with other pathological characteristics of the tumor, such as tumor size, lymphovascular invasion, tumor grade, lymph node metastasis, and resection margin status. Diabetic patients had a significantly lower frequency of abdominal pain (P = 0.01), but a slightly higher frequency of weight loss (P = 0.078) as early symptoms of their cancer. Both diabetes and perineural invasion were related to worse survival and increased risk of death after adjusting for tumor grade and margin and node status (P = 0.036 and 0.019, respectively). The observed associations of diabetes and perineural invasion as well as reduced frequency of pain as early symptom of pancreatic cancer support the hypothesis that diabetes may contribute to pancreatic progression via the mechanism of nerve damage.
Topics: Adenocarcinoma; Adult; Aged; Diabetes Complications; Diabetes Mellitus; Female; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Pancreas; Pancreatic Neoplasms; Prognosis; Proportional Hazards Models; Retrospective Studies
PubMed: 23342285
DOI: 10.1002/cam4.43 -
Journal of the Chinese Medical... Jun 2017Perineural invasion is a pathological feature that may affect cancer cell progression and thus can result in prognostic impacts, especially in oral squamous cell...
BACKGROUND
Perineural invasion is a pathological feature that may affect cancer cell progression and thus can result in prognostic impacts, especially in oral squamous cell carcinoma (OSCC). However, factors regulating perineural invasion during OSCC remain obscure.
METHODS
Expression of miR-21 and phosphatase and tensin homolog was checked in surgical specimens from cases of OSCC. The results were analyzed for histopathologic factors, including perineural invasion and clinical prognosis.
RESULTS
One-hundred cases of OSCC patients were enrolled in this study. High expression of miR-21 was related to perineural invasion and worse prognosis in OSCC patients.
CONCLUSION
miR-21 was an independent factor of disease survival of OSCC. miR-21/phosphatase and tensin homolog disregulation was related to perineural invasion.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Male; MicroRNAs; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; PTEN Phosphohydrolase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Squamous Cell Carcinoma of Head and Neck
PubMed: 28254348
DOI: 10.1016/j.jcma.2017.01.003 -
Cancers Dec 2021Adenoid cystic carcinoma of the head and neck is an uncommon malignancy that can arise in the major or minor salivary glands. Perineural invasion (PNI) is an extremely... (Review)
Review
Adenoid cystic carcinoma of the head and neck is an uncommon malignancy that can arise in the major or minor salivary glands. Perineural invasion (PNI) is an extremely frequent finding in cases of adenoid cystic carcinoma (ACC) that can be associated with significant patient morbidity and poor prognosis. By contrast, ACC rarely demonstrates lymphovascular space invasion thereby making PNI the major avenue for metastasis and a driver of treatment rationale and design. Radiotherapy is often utilized post-operatively to improve locoregional control or as a primary therapy in unresectable disease. Here we aim to review the role of radiotherapy in the management of this malignancy with a focus on target delineation and treatment regimens in the definitive, recurrent, and metastatic settings.
PubMed: 34944955
DOI: 10.3390/cancers13246335 -
World Journal of Gastroenterology Mar 2014To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological...
AIM
To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological features, perineural invasion, and prognosis.
METHODS
Pancreatic cancer tissues (including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor) were taken from 42 patients who were undergoing a partial duodenopancreatectomy. MK and syndecan-3 proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method, and analyzed for their correlation with clinicopathological features, perineural invasion, and prognosis. Associations of neural invasion with aggressive characteristics of pancreatic cancer and the presence of perineural invasion were assessed by two independent observers blinded to the patient status.
RESULTS
MK and syndecan-3 were found in 26 (61.9%) and 24 (57.1%) specimens, respectively. MK and syndecan-3 expression was associated with perineural invasion (P = 0.018 and 0.031, respectively). High MK expression was closely associated with advanced tumor, node and metastasis stage (P = 0.008), lymph node metastasis (P = 0.042), and decreased postoperative survival at 3 years (51.0% vs 21.8%, P = 0.001). Syndecan-3 levels were correlated with tumor size (P = 0.028). Patients who were syndecan-3 negative had a higher cumulative survival rate than those who were positive, but the difference was not significant (44.0% vs 23.0%, P > 0.05).
CONCLUSION
MK and syndecan-3 are frequently expressed in pancreatic cancer and associated with perineural invasion. High expression of MK and syndecan-3 may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Pancreatic Ductal; Case-Control Studies; China; Female; Humans; Male; Middle Aged; Midkine; Neoplasm Invasiveness; Nerve Growth Factors; Pancreas; Pancreatic Neoplasms; Syndecan-3
PubMed: 24659893
DOI: 10.3748/wjg.v20.i11.3018 -
Journal of Neurological Surgery. Part... Apr 2016The surgical management of perineural spread of head and neck cancers has become an integral part in the contemporary treatment of this pathology. We now understand that...
The surgical management of perineural spread of head and neck cancers has become an integral part in the contemporary treatment of this pathology. We now understand that tumour spreads within the epineurium and in a continuous fashion. We also can rely on the accuracy of magnetic resonance neurography in detecting and defining the extent of disease. With modern skull base techniques and a greater understanding of the anatomy in this region, specific operations can be designed to help eradicate disease. We review the current approaches and techniques used that enable us to better obtain tumour free margins and hence improve survival.
PubMed: 27123390
DOI: 10.1055/s-0036-1579751 -
Biomedicines Sep 2023Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display...
Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.
PubMed: 37892990
DOI: 10.3390/biomedicines11102616 -
Journal of Pain Research 2023Glucocorticoids are commonly used as regional anesthesia adjuvants to improve blockade quality and duration. There are limited data in the literature regarding the...
PURPOSE
Glucocorticoids are commonly used as regional anesthesia adjuvants to improve blockade quality and duration. There are limited data in the literature regarding the potential systemic effects and safety of perineural glucocorticoids. This study examines the effects of perineural glucocorticoids on serum glucose, potassium, and white blood cell count (WBC) in the immediate postoperative period after primary total hip arthroplasty (THA).
PATIENTS AND METHODS
A retrospective cohort study was carried out at a tertiary academic medical center utilizing electronic health records of 210 patients who underwent THA, for which patients received either a periarticular local anesthetic injection alone (PAI, N=132) or additional peripheral nerve blocks (PNB, N=78) containing 10 mg dexamethasone and 80 mg methylprednisolone acetate (PAI+PNB). The primary outcome was change in serum glucose from a preoperative baseline on postoperative days (POD) 1, 2, and 3. Secondary outcomes included changes in WBC and serum potassium.
RESULTS
The change in serum glucose from baseline was found to be significantly higher in the PAI+PNB group compared to the PAI group on POD 1 (mean difference 19.87 mg/dL, 95% CI [12.42, 27.32]; <0.001) and POD 2 (mean difference 17.5 mg/dL, 95% CI [9.66, 25.44], <0.001). No significant difference was found on POD 3 (mean difference -8.18 mg/dL, 95% CI [-19.07, 2.70], =0.14). Statistically significant but clinically insignificant differences were detected in serum potassium in the PAI+PNB group compared to the PAI group on POD1 (mean difference 0.16 mEq/L, 95% CI [0.02, 0.30], =0.03) and WBC on POD 2 (mean difference 3.18 × 1000/mm, 95% CI [2.14, 4.22], <0.001).
CONCLUSION
Patients who underwent THA and received PAI+PNB with glucocorticoid adjuvants demonstrated higher elevations in serum glucose for the first two PODs compared to patients who received PAI alone. These differences resolved by a third POD and are likely to be of no clinical significance.
PubMed: 36846205
DOI: 10.2147/JPR.S395336 -
International Journal of Particle... 2021To report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion.
PURPOSE
To report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion.
MATERIALS AND METHODS
We reviewed the medical records of patients who received definitive or postoperative proton therapy for nonmelanoma skin cancer with clinical perineural invasion at our institution and updated patient follow-up when possible. All patients were treated with curative intent with or without the delivery of concurrent systemic therapy. We report disease control rates and the rates of late toxicity among this cohort.
RESULTS
Twenty-six patients treated between 2008 and 2017 were included in the analysis. Following proton therapy, the 3-year overall, cause-specific, and disease-free survival rates were 59%, 73%, and 60%, respectively. The 3-year local control, local regional control, and distant metastasis-free survival rates were 80%, 65%, and 96%, respectively. On univariate analysis, surgical resection before radiation therapy significantly improved local regional control rates at 3 years (55% versus 86%; = .04). Grade 3+ late toxicities occurred in 13 patients (50%) and the most common toxicities included grade 3+ keratitis of the ipsilateral eye, which occurred in 4 patients (15%) and grade 3+ brain necrosis in 4 patients (15%).
CONCLUSION
Proton therapy is effective in the management of nonmelanoma skin cancer with clinical perineural invasion. Although disease control and complication rates compare favorably to those previously published for photon-based radiation therapy, the risk for late toxicity is significant and patients should be appropriately counseled.
PubMed: 34285954
DOI: 10.14338/IJPT-20-00062.1