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Cancer Management and Research 2020To investigate the clinicopathological and prognostic factors related to early gastric cancer recurrence after curative resection.
PURPOSE
To investigate the clinicopathological and prognostic factors related to early gastric cancer recurrence after curative resection.
PATIENTS AND METHODS
Between October 2006 and August 2018, a total of 149 patients with recurrence of gastric cancer/adenocarcinoma of the esophagogastric junction after curative resection were enrolled from our treatment group. A retrospective clinical analysis was performed on these patients with gastric cancer recurrence after curative resection.
RESULTS
Among the 149 patients, 99 (66.4%) had only one recurrence pattern, and 50 (33.6%) had multiple recurrence patterns. The median recurrence-free survival (RFS) was 18.2 months (95% CI 15.0-21.4). Ninety-four patients (63.1%) experienced early recurrence (recurrence within 24 months after curative resection), and 55 patients (36.9%) experienced late recurrence (recurrence beyond 24 months after curative resection). The univariate analysis showed that perineural invasion (P=0.002), depth of invasion (P=0.026), postoperative chemotherapy (P=0.036) and postoperative complications (P=0.004) were significant factors associated with early recurrence after curative resection for gastric cancer. Perineural invasion (P=0.003), postoperative chemotherapy (P=0.036) and postoperative complications (P=0.042) were independent factors associated with early recurrence after curative resection in the multivariate analysis. The survival analysis showed that perineural invasion (P=0.011) and postoperative complications (P=0.007) were independent prognostic factors. The median survival time of early recurrence patients was significantly shorter than that of late recurrence patients (25.4 vs 62.9 months, P<0.001).
CONCLUSION
Perineural invasion, postoperative chemotherapy and postoperative complications were independent factors associated with early recurrence after curative resection. Patients with early recurrence after curative resection had poorer survival.
PubMed: 32904660
DOI: 10.2147/CMAR.S264582 -
Cancers Aug 2022We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or...
Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.
We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.
PubMed: 36077649
DOI: 10.3390/cancers14174112 -
The Journal of Clinical and Aesthetic... Jan 2022Mohs micrographic surgery (MMS) is the gold standard treatment for non-melanoma skin cancer (NMSC). However, NMSC recurrence may occur in a small proportion of patients.... (Review)
Review
OBJECTIVE
Mohs micrographic surgery (MMS) is the gold standard treatment for non-melanoma skin cancer (NMSC). However, NMSC recurrence may occur in a small proportion of patients. The aim of this study was to identify histopathologic features seen on the final stage of previous MMS, which may increase the risk of NMSC recurrence.
METHODS
This was a single-institution retrospective study of 39 recurrent basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), which were treated with MMS. Slides from the final stage of previous MMS were reviewed by two board-certified dermatopathologists for the following histopathologic features: perineural inflammation, dense inflammation, mucin, ruptured follicle, actinic keratosis, and missing tissue.
RESULTS
Twenty recurrent BCCs and 19 recurrent SCCs were included. Histopathologic features identified on the final stage of previous MMS included missing tissue from the epidermis, dermis, and/or subcutis (69%), actinic keratosis (51%), perineural inflammation (10%), and dense inflammation (8%). Ruptured follicle was present in one BCC case, and mucin was not identified in any cases.
LIMITATIONS
Limitations include retrospective study design, small number of recurrent cases, single institution, and lack of a control group consisting of NMSC cases which did not recur after MMS.
CONCLUSION
Mohs surgeons should carefully evaluate NMSC frozen sections for the presence of missing tissue, actinic keratosis, perineural inflammation, and dense inflammation as these histopathologic features may be associated with tumor recurrence. It is of paramount importance to acquire high quality frozen sections for thorough margin evaluation.
PubMed: 35309269
DOI: No ID Found -
Journal of Clinical Medicine May 2021(1) Background: Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy. Besides tumor, nodal, and metastatic status, the UICC TNM classification describes further...
(1) Background: Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy. Besides tumor, nodal, and metastatic status, the UICC TNM classification describes further parameters such as lymphangio- (L0/L1), vascular (V0/V1/V2), and perineural invasion (Pn0/Pn1). The aim of this study was to analyze the influence of these parameters on recurrence and survival. (2) Methods: All surgical explorations for patients with ICC between January 2008 and June 2018 were collected and further analyzed in our institutional database. Statistical analyses focused on perineural, lymphangio-, and vascular invasion examined histologically and their influence on tumor recurrence and survival. (3) Results: Of 210 patients who underwent surgical exploration, 150 underwent curative-intended resection. Perineural invasion was present in 41, lymphangioinvasion in 21, and vascular invasion in 37 patients (V1 = 34, V2 = 3). Presence of P1, V+ and L1 was significantly associated with positivity of each other of these factors ( < 0.001, each). None of the three parameters showed direct influence on tumor recurrence in general, but perineural invasion influenced extrahepatic recurrence significantly ( = 0.019). Whereas lymphangio and vascular invasion was neither associated with overall nor recurrence-free survival, perineural invasion was significantly associated with a poor 1-, 3- and 5-year overall survival (OS) of 80%, 35%, and 23% for Pn0 versus 75%, 23%, and 0% for Pn1 ( = 0.027). Concerning recurrence-free survival (RFS), Pn0 showed a 1-, 3- and 5-year RFS of 42%, 18%, and 16% versus 28%, 11%, and 0% for Pn1, but no significance was reached ( = 0.091). (4) Conclusions: Whereas lymphangio- and vascular invasion showed no significant influence in several analyses, the presence of perineural invasion was associated with a significantly higher risk of extrahepatic tumor recurrence and worse overall survival.
PubMed: 34070745
DOI: 10.3390/jcm10112426 -
Journal of Surgical Oncology Mar 2021We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative...
BACKGROUND AND OBJECTIVES
We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative therapy.
METHODS
Patients with gastric cancer treated with preoperative therapy and potentially curative resection were stratified according to the presence of LVI, PNI, or both. Kaplan-Meier and Cox regression analyses were used to evaluate the impact on overall survival (OS) and disease-free survival (DFS).
RESULTS
The study included 281 patients, of whom 93 (33%) had LVI, 69 (25%) had PNI, 51 (18%) had both LVI and PNI, and 170 (61%) had neither. LVI and PNI were each associated with higher ypT and ypN categories and more positive lymph nodes (all p < .001), associations that were emphasized with both factors present. On multivariable analyses, ypN (p < .001) and concurrent LVI/PNI (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.55-4.45; p = .001) were predictive of OS and DFS (ypN: p < .001; both LVI/PNI: HR: 2.27; 95% CI: 1.34-3.82; p = .002).
CONCLUSIONS
Gastric cancer patients with concurrent LVI and PNI after preoperative therapy have more advanced disease and worse survival outcomes than patients with neither or only one of these factors.
Topics: Adenocarcinoma; Chemoradiotherapy; Female; Follow-Up Studies; Humans; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Perineum; Preoperative Care; Prognosis; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Survival Rate
PubMed: 33400838
DOI: 10.1002/jso.26367 -
Pain Reports 2021Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in...
Analgesic effect of perineural local anesthetics, steroids, and conventional medical management for trauma and compression-related peripheral neuropathic pain: a retrospective cohort study.
INTRODUCTION
Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear.
OBJECTIVES
The objectives of this retrospective study were to determine the analgesic benefits of adding a combination of perineural local anesthetic and steroids (LA-S) to CMM compared with CMM alone in patients who had moderate-to-severe refractory NP after trauma to the ankle and the foot.
METHODS
Health care records of 60 patients in exposed (3 injections of perineural LA-S at weekly intervals with CMM) and 60 in unexposed (CMM) cohorts were reviewed. Data on patient characteristics, pain, and mental and physical function were extracted at baseline and at the postintervention follow-up. Data were analyzed to evaluate analgesic benefit from the study interventions and the impact of baseline characteristics.
RESULTS
Perineural LA-S with CMM cohort had lower pain numerical rating scale scores at 1 to 3 months after the intervention as compared to the CMM alone cohort (5.50 [interquartile range 4.00-7.00] and 7.00 [interquartile range 5.00-8.00], respectively; < 0.01). However, multivariable analysis did not show an independent beneficial analgesic effect with the addition of perineural LA-S to CMM compared with CMM alone. A greater severity of preintervention catastrophizing (each unit increase in pain catastrophizing score increased pain score at follow-up by 0.04, 95% confidence interval: 0.01-0.07) was associated with reduction in the analgesic benefit.
CONCLUSION
Perineural local anesthetic and steroid injections do not confer an analgesic benefit for trauma- or compression-related peripheral NP.
PubMed: 34278164
DOI: 10.1097/PR9.0000000000000945 -
International Journal of General... 2023Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to...
BACKGROUND
Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood.
METHODS
In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes.
RESULTS
Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways.
CONCLUSION
Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.
PubMed: 37822345
DOI: 10.2147/IJGM.S428590 -
Advanced Biology Sep 2022Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural...
Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural invasion (PNI). OSCC has higher rates of PNI than other cancer subtypes, with PNI present in 80% of tumors. Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co-opt different components of the neurotrophin pathway in metastasis, PNI, and pain.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplastic Processes; Nerve Growth Factors; Nerve Tissue Proteins; Pain; Receptor Protein-Tyrosine Kinases; Receptor, Nerve Growth Factor; Receptor, trkA; Receptors, Nerve Growth Factor; Squamous Cell Carcinoma of Head and Neck
PubMed: 35925599
DOI: 10.1002/adbi.202200190 -
Frontiers in Cell and Developmental... 2020The overarching view of current tumor therapies simplifies cancer to a cell-biology problem in which neoplasms are caused solely by malignant cells and the exploration... (Review)
Review
The overarching view of current tumor therapies simplifies cancer to a cell-biology problem in which neoplasms are caused solely by malignant cells and the exploration of carcinogenesis and tumor progression largely focuses on somatic mutations and other genetic abnormalities of cancer cells. The limited therapeutic response indicates that cancer is driven not only by endogenous oncogenic factors and reciprocal interactions within the tumor microenvironment, but also by complex systemic processes. Homeostasis is the fundamental premise of health, and is maintained by systemic regulation of neuro-endocrine-immune axis. Cancer is also a systemic disease that manifested by dysfunction of the nervous, endocrine, and immune systems. Multiple axes of regulation exist in cancer, including central-, organ-, and microenvironment-level manipulation. At each specific regulatory level, the tridirectional communication among the nervous, endocrine, and immune factors transmit flexible signaling to induce proliferation, invasion, reprogrammed metabolism, therapeutic resistance, and other malignant phenotypes of cancer cells, resulting in the extremely poor prognosis of this lethal disease. Understanding this coordinated signaling network will enable the development of new approaches for cancer treatment via behavioral and pharmacological interventions.
PubMed: 33117814
DOI: 10.3389/fcell.2020.586757 -
British Journal of Anaesthesia Aug 2020Liposomal bupivacaine (Exparel®) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve...
BACKGROUND
Liposomal bupivacaine (Exparel®) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve toxicity and clinical effectiveness of perineural Exparel® alone or with added dexamethasone in a mouse model.
METHODS
We assigned 98 mice receiving a perineural sciatic nerve injection into seven groups: sham (n=14, perineural saline), B (n=14, perineural bupivacaine), BDIP (n=14, perineural bupivacaine + intraperitoneal dexamethasone), BDPN (n=14, perineural bupivacaine + perineural dexamethasone), E (n=14, perineural Exparel®), EDIP (n=14, perineural Exparel® + intraperitoneal dexamethasone), and EDPN (n=14, perineural Exparel® + perineural dexamethasone). The duration of thermoalgesic and motor block was evaluated in 49 mice (seven mice randomly selected by group) every 30 min until recovery. Mice were killed for sciatic nerve histological assessment at 14 or 28 days.
RESULTS
The median duration of motor block was 90, 120, 120, 120, 180, and 180 min and the duration of thermoalgesic block was 240, 300, 360, 360, 360, and 420 min for groups B, BDIP, BDPN, E, EDIP, and EDPN, respectively. The B group mice showed mild neural inflammation at 14 days and the E group mice showed mild neural inflammation at 28 days. Addition (intraperitoneal or perineural) of dexamethasone reduced neural inflammation induced by bupivacaine, whereas only perineural dexamethasone reduced neural inflammation induced by Exparel®.
CONCLUSIONS
Perineural or systemic dexamethasone had a protective effect against the neural inflammation induced by bupivacaine, and perineural dexamethasone attenuated delayed inflammation induced by perineural Exparel®.
Topics: Anesthetics, Local; Animals; Anti-Inflammatory Agents; Bupivacaine; Dexamethasone; Disease Models, Animal; Drug Interactions; Inflammation; Male; Mice; Mice, Inbred C57BL; Time
PubMed: 32593455
DOI: 10.1016/j.bja.2020.04.091