Re-Irradiation With Proton Beam Therapy for Localized Perineural Spread Following Presacral Recurrence in Sigmoid Colon Cancer: A Case Report.

This report describes the effective management of localized perineural spread (PNS) to the sacral peripheral nerves following a presacral recurrence of colon cancer using proton beam therapy (PBT). The patient, a male in his 60s with a history of sigmoid colon cancer treated with laparoscopic Hartmann's procedure, presented with presacral recurrence two years post-surgery. Radical resection was deemed infeasible, leading to a combined treatment of PBT (75 Gy relative biological effectiveness (RBE) in 25 fractions) and capecitabine. However, three years post-PBT, magnetic resonance imaging revealed swelling of the left S2 nerve with abnormal fluorodeoxyglucose uptake, indicating localized PNS. Re-irradiation with PBT (75 Gy RBE in 25 fractions) was conducted, carefully considering the overlap with the previous PBT field and aiming to minimize dosage to adjacent organs. At 1.5 years post-reirradiation, the patient remained free of recurrence. This case underscores the potential efficacy of PBT and emphasizes the need for further research to assess its broader applicability in comparable situations.

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 (p = 0.01). Moreover, the occurrence of DGE is statistically associated with male gender (p = 0.001), worse grade of postoperative fistula (p < 0.01), and the presence of postoperative haemorrhage (p = 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 (p = 0.018 and p = 0.028, respectively), absence of perineural infiltrations (p = 0.005 and p = 0.003, respectively), better grade of postoperative fistula (p < 0.001), and absence of postoperative haemorrhage (p < 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.

Periampullary cancer and neurological interactions: current understanding and future research directions.

Periampullary cancer is a malignant tumor occurring around the ampullary region of the liver and pancreas, encompassing a variety of tissue types and sharing numerous biological characteristics, including interactions with the nervous system. The nervous system plays a crucial role in regulating organ development, maintaining physiological equilibrium, and ensuring life process plasticity, a role that is equally pivotal in oncology. Investigations into nerve-tumor interactions have unveiled their key part in controlling cancer progression, inhibiting anti-tumor immune responses, facilitating invasion and metastasis, and triggering neuropathic pain. Despite many mechanisms by which nerve fibers contribute to cancer advancement still being incompletely understood, the growing emphasis on the significance of nerves within the tumor microenvironment in recent years has set the stage for the development of groundbreaking therapies. This includes combining current neuroactive medications with established therapeutic protocols. This review centers on the mechanisms of Periampullary cancer's interactions with nerves, the influence of various types of nerve innervation on cancer evolution, and outlines the horizons for ongoing and forthcoming research.

Intravenous injection of dexamethasone is non-inferior to perineural administration for popliteal sciatic nerve and saphenous nerve blocks: A randomized, controlled, triple-blind study.

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18-75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0-48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, -1.7; 95% CI, -3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P < 0.001). Conditions for establishing non-inferiority were met. Conclusions: Our findings indicate that a single 10-mg intravenous dose of dexamethasone was noninferior to the combined dose of ropivacaine plus deaxmethasone in terms of duration of analgesia for foot and ankle surgery.

Perineural invasion in cervical cancer: A multicenter retrospective study.

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Perineural 5% dextrose versus corticosteroid injection in non-surgical carpal tunnel syndrom treatment.

Background and purpose:

We aimed to investigate the difference of clinical and electrophysiological improvement between perineural corticosteroid injection therapy (PCIT) and perineural 5% dextrose injection therapy (5%PDIT) in carpal tunnel syndrome (CTS).

Total of 92 wrists that were diagnosed as mild-to-moderate idiopathic CTS and completed their follow-up were included in our study. The severity of pain, symptom severity and functional status were asses­sed by visual analog scale (VAS) and the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores for treatment effectiveness. Randomized wrists were administered PCIT or 5%PDIT accompanied by ultrasound guidance. VAS, BCTQ scores and the electro­physiological study repeated before and after treatment at the 1st and 6th months after perineural injection therapies (PITs) were recorded.

Compared with baseline data, within groups there was significant improvement in VAS, BCTQ severity and function scores at 1st and 6th months follow-up (all p < 0.001). Considerable advance were detected in the median sensory nerve conduction velocity (SNCV) when pretreatment values were compared with posttreatment first month in both groups (p = 0.01; p < 0.001, respectively). No significant change occurred in median distal motor latency (DML) values between the 1st and 6th months in the groups (p = 0.095; p = 0.113, respectively). No significant difference was observed bet­ween 5%PDIT and PCIT groups.

Clinical and electrophysiologic improvement in CTS began from 1st month after PCIT and 5%PDIT. At the 6th month follow-up of the patients, 5%PDIT and PCIT had similar therapeutic effects. As a result, we can consider the replacement of PCIT with 5%PDIT in mild-to-moderate CTS patients especially in those who are hesitant because of the corticosteroid’s adverse effects.

The value of machine learning based on CT radiomics in the preoperative identification of peripheral nerve invasion in colorectal cancer: a two-center study.

BACKGROUND: We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). METHODS: A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. RESULTS: The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the "one standard error" rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the "one standard error" rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. CONCLUSIONS: Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. CRITICAL RELEVANCE STATEMENT: The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. KEY POINTS: • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients.

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Surgical Intervention is Associated with Improvement in Health-Related Quality of Life Outcomes in Patients with Symptomatic Sacral Tarlov Cysts: Results from a Prospective Longitudinal Cohort Study.

OBJECTIVE: The treatment of symptomatic Tarlov cysts remains a controversial topic within neurosurgery. We describe our experience with patients who underwent surgical intervention for sacral Tarlov cysts at a single institution. General and disease-specific outcome measures were used to assess health-related quality of life. METHODS: Patients who underwent surgical treatment for one or more sacral Tarlov cysts between 2018 and 2021 were included. The Tarlov Cyst Quality of Life (TCQoL), a validated disease-specific measure, was the primary outcome of the study. Secondary outcomes included general outcome measures: 36-Item Short Form Survey, the Oswestry Disability Index, and Visual Analog Scale. Patients were followed at 3, 6, and 12 months postoperative. Repeated measures analyses were used to assess change from preoperative to 12 months postoperative. RESULTS: Data were obtained from 144 patients who underwent surgery for sacral Tarlov cysts, average age 52.3 ± 11.3 years, 90.3% female. Patients reported significant mean improvement on the TCQoL over time (preoperative 3.2±0.1; 3-months postoperative 2.1±0.1; 6-months 1.9±0.1; 12-months 1.9±0.1; P< 0.001). Patient age and duration of symptoms were not associated with outcome. 82.3% of patients reported improvement on TCQoL. There was not a significant difference in the proportion of patients reporting improvement on TCQoL by cyst size (small 90.9% vs. large 77.9%; P = 0.066). CONCLUSION: Our longitudinal series demonstrated patient-reported improvement following surgery for symptomatic sacral Tarlov cysts using a validated disease-specific health-related quality of life scale through 12 months following surgery. Patient age and preoperative duration of symptoms were not correlated with outcome.

Molecular pathway of pancreatic cancer-associated neuropathic pain.

The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer-associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene-related peptide which is also involved in pain. Matrix metalloproteases are the zinc-associated proteases enzymes which activates proinflammatory interleukin-1ß into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below.

A prediction nomogram for perineural invasion in colorectal cancer patients: a retrospective study.

BACKGROUND: Perineural invasion (PNI), as the fifth recognized pathway for the spread and metastasis of colorectal cancer (CRC), has increasingly garnered widespread attention. The preoperative identification of whether colorectal cancer (CRC) patients exhibit PNI can assist clinical practitioners in enhancing preoperative decision-making, including determining the necessity of neoadjuvant therapy and the appropriateness of surgical resection. The primary objective of this study is to construct and validate a preoperative predictive model for assessing the risk of perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 335 patients diagnosed with colorectal cancer (CRC) at a single medical center were subject to random allocation, with 221 individuals assigned to a training dataset and 114 to a validation dataset, maintaining a ratio of 2:1. Comprehensive preoperative clinical and pathological data were meticulously gathered for analysis. Initial exploration involved conducting univariate logistic regression analysis, with subsequent inclusion of variables demonstrating a significance level of p < 0.05 into the multivariate logistic regression analysis, aiming to ascertain independent predictive factors, all while maintaining a p-value threshold of less than 0.05. From the culmination of these factors, a nomogram was meticulously devised. Rigorous evaluation of this nomogram's precision and reliability encompassed Receiver Operating Characteristic (ROC) curve analysis, calibration curve assessment, and Decision Curve Analysis (DCA). The robustness and accuracy were further fortified through application of the bootstrap method, which entailed 1000 independent dataset samplings to perform discrimination and calibration procedures. RESULTS: The results of multivariate logistic regression analysis unveiled independent risk factors for perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC). These factors included tumor histological differentiation (grade) (OR = 0.15, 95% CI = 0.03-0.74, p = 0.02), primary tumor location (OR = 2.49, 95% CI = 1.21-5.12, p = 0.013), gross tumor type (OR = 0.42, 95% CI = 0.22-0.81, p = 0.01), N staging in CT (OR = 3.44, 95% CI = 1.74-6.80, p < 0.001), carcinoembryonic antigen (CEA) level (OR = 3.13, 95% CI = 1.60-6.13, p = 0.001), and platelet-to-lymphocyte ratio (PLR) (OR = 2.07, 95% CI = 1.08-3.96, p = 0.028).These findings formed the basis for constructing a predictive nomogram, which exhibited an impressive area under the receiver operating characteristic (ROC) curve (AUC) of 0.772 (95% CI, 0.712-0.833). The Hosmer-Lemeshow test confirmed the model's excellent fit (p = 0.47), and the calibration curve demonstrated consistent performance. Furthermore, decision curve analysis (DCA) underscored a substantial net benefit across the risk range of 13% to 85%, reaffirming the nomogram's reliability through rigorous internal validation. CONCLUSION: We have formulated a highly reliable nomogram that provides valuable assistance to clinical practitioners in preoperatively assessing the likelihood of perineural invasion (PNI) among colorectal cancer (CRC) patients. This tool holds significant potential in offering guidance for treatment strategy formulation.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

Effectiveness of perineural administration of dexamethasone with lidocaine on onset time of sensory block and early postoperative analgesia in axillary brachial plexus block: a prospective cohort study, Ethiopia.

Introduction: The axillary brachial plexus block is a popular nerve block for forearm, wrist, and hand surgery. The aim of this study was to assess the effectiveness of perineural administration of dexamethasone as an adjunct to lidocaine with adrenaline on the onset of sensory block and early postoperative analgesia in trans-arterial axillary brachial plexus block. Methodology: This single-centered prospective cohort study recruited 68 adult patients, 34 in each groups. The frequently used 8 mg dexamethasone combined with 1% lidocaine and adrenaline was investigated. The normality of the data was checked using the Shapiro-Wilk test. An independent t-test was used to compare the mean values of symmetric numeric data. Categorical variables between the two groups were analyzed using χ2. The Mann-Whitney U test and Kaplan-Meier method using the log-rank test were used to compare asymmetric numeric data, and a P-value of <0.05 was considered as significant. Results: The median onset time of sensory block was comparable between the nonexposed (24(6) min) and exposed group (24(6) min) (P=0.068). However, the duration of sensory block was significantly longer in the exposed group (235.5±37.51 min) than the nonexposed group (172.76±28.19 min) (P<0.001). The time to the first analgesic request was significantly longer in the exposed than the nonexposed group (P<0.01). Postoperative pain scores were significantly lower at 4 and 8 h in the exposed group (P<0.05). Conclusion and recommendations: The addition of 8 mg dexamethasone to 1% lidocaine with adrenaline solution in trans-arterial axillary brachial plexus block for ambulatory elective hand, wrist, and forearm surgeries prolonged the duration of sensory blockade and the first analgesic request time but did not reduce the onset time of sensory block. The authors recommend the addition of 8 mg dexamethasone to 1% lidocaine with adrenaline solution to prolong the duration of sensory block and the first analgesic request time.

Clinical significance of location of perineural cancer invasion detected on prostate needle core biopsy.

The clinical impact of site-specific perineural invasion (PNI) in prostate cancer remains poorly understood. We compared radical prostatectomy findings and oncologic outcomes in 434 patients with single-site PNI on systematic sextant biopsy. PNI was present in the right apex (n = 62; 14%), right mid (n = 70; 16%), right base (n = 89; 21%), left apex (n = 64; 15%), left mid (n = 58; 13%), and left base (n = 91; 21%). There were no significant differences in biopsy or prostatectomy findings, when comparing apex vs. mid vs. base PNI. Univariate analysis revealed that apex-localized PNI was associated with a significantly higher risk of progression, compared with base (P = 0.037) or mid/base (P = 0.024) PNI. Multivariable analysis showed that apex-localized PNI was an independent risk factor for progression (hazard ratio 2.049, P = 0.002). Among biopsies demonstrating PNI at one sextant site, apex-localized PNI is independently associated with poorer prognosis, though not worse histopathologic features on prostatectomy, compared with mid or base PNI.

Mapping functional to morphological variation reveals the basis of regional extracellular matrix subversion and nerve invasion in pancreatic cancer.

Intratumor morphological heterogeneity of pancreatic ductal adenocarcinoma (PDAC) predicts clinical outcomes but is only partially understood at the molecular level. To elucidate the gene expression programs underpinning intratumor morphological variation in PDAC, we investigated and deconvoluted at single cell level the molecular profiles of histologically distinct clusters of PDAC cells. We identified three major morphological and functional variants that co-exist in varying proportions in all PDACs, display limited genetic diversity, and are associated with a distinct organization of the extracellular matrix: a glandular variant with classical ductal features; a transitional variant displaying abortive ductal structures and mixed endodermal and myofibroblast-like gene expression; and a poorly differentiated variant lacking ductal features and basement membrane, and showing neuronal lineage priming. Ex vivo and in vitro evidence supports the occurrence of dynamic transitions among these variants in part influenced by extracellular matrix composition and stiffness and associated with local, specifically neural, invasion.

Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer.

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K-AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

Treating Lateral Epicondylopathy With Dry Needling and Exercise: A Case Series.

CONTEXT: Lateral epicondylopathy (LE) is a common overuse injury affecting elbow, wrist, and hand function. It is characterized by weakness and pain in the muscles and tendons of the forearm responsible for the extension of your wrist and fingers. Trigger point dry needling is a technique reported to be beneficial in managing pain and dysfunction after LE diagnosis. LE is also commonly treated with conservative treatment, such as joint and soft tissue mobilization, self-care home programs, and anti-inflammatory use. We explored a different dry needling approach consisting of in situ dry needling with electric stimulation combined with targeted therapeutic exercise to treat LE in 3 cases. CASE PRESENTATION: Three patients were referred for dry needling once a week for 6 weeks and home-based exercise therapy for LE. They were clinically evaluated using grip strength, a visual analog scale to assess pain, and Patient-Rated Tennis Elbow Evaluation Test scores. These were measured at 4 time points (weeks 0, 2, 4, and 6). MANAGEMENT AND OUTCOMES: The dry needling intervention incorporated 8 locations in the upper-extremity with 2 electric stimulation channels. The patients had reduced pain as measured by a visual analog scale, increased function as measured by the Patient-Rated Tennis Elbow Evaluation Test, and increased grip strength over 6 weeks. CONCLUSIONS: This case series illustrates the use of dry needling and a home exercise program to provide a favorable outcome in a patient with LE. Patients had an 80% to 100% reduction in pain and similar improvements in function that were significantly beyond the minimum clinically important difference. This dry needling approach is a safe and effective treatment of LE in the short term.

Perineural invasion score system and clinical outcomes in resected pancreatic cancer patients.

BACKGROUND/OBJECTIVES: Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients. METHODS: Five histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Forty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months vs. not reached (NR) (p = 0.258), while the OS was 19 months vs. NR (p = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS vs. <6 PNI + patients (29 vs. 11 months, p < 0.001) and <6 PNI+ and PNI- patients (43 vs. 11 months, p < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS vs. <6 PNI+ and PNI- patients (13 vs. 6 months, p = 0.022). CONCLUSIONS: We report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.

Assessment of perineural spread in advanced cutaneous squamous cell carcinomas treated with immunotherapy.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system. METHODS: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). RESULTS: Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT. CONCLUSIONS: PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.

Peeping Beyond TNM Stage: Prognostic Factors Affecting Oncological Outcomes in Surgically Treated Early Oral Cancer.

Surgery is the primary modality for the treatment of early oral cancer. The present study aims to evaluate the oncological outcomes, patterns of failure, and prognostic predictors of recurrence in patients of early oral cancer (Stage I and II) treated by surgery alone. It is a single institutional, observational retrospective cohort study conducted from 2012 to 2017.The study was approved by institutional ethics committee. All consecutive patients who underwent upfront curative surgery alone (wide excision of tumour + neck dissection) for pathologically proven early oral cavity SCC(Squamous Cell Carcinoma) pT1-2N0 were included in the study. 113 patients were included in the study after a median follow-up of 58.2 months. The median age was 58.5 years. 25 patients were stage I, and 88 patients were stage II. The most common subsite was buccal mucosa. There were 31 recurrences and 24 deaths. Using Kaplan Meier method, 3 and 5 year overall survival was 92% and 71.8%, respectively, while 3 year and 5 year recurrence-free survival was 77.9% and 69.4%, respectively. Perineural invasion and poor differentiation affected recurrence-free survival significantly (p value < 0.05). More than one-fourth of surgically treated early oral SCC patients developed recurrence. Presence of poorly differentiated histology and the perineural invasion were the high risk factors which hampered the recurrence free survival. High consumption of betel quid consumption in this part of the world leads to differences in the involved subsite from the Western literature. Adding adjuvant treatment in the presence of these adverse histopathological features may improve prognosis. Randomised studies are warranted to answer this dilemma. Level of Evidence IV.