[Association of peripheral nerve invasion with clinicopathological factors and prognosis of colorectal cancer].

OBJECTIVE: To investigate the association of peripheral nerve invasion (PNI) with clinicopathological factors and prognosis of colorectal cancer. METHODS: Clinicopathological data and Surgical specimens of 372 colorectal cancer patients who underwent radical resection from January 2011 to June 2012 in The Second Affiliated Hospital of Harbin Medical University were collected. Histopathological evaluation of tissue samples was conducted with hematoxylin and eosin-stained sections. PNI was considered positive when cancer cells were observed inside the nerve sheath, or when at least 33% of the nerve periphery was surrounded by cancer cells. The relationship between PNI and clinicopathological factors of colorectal cancer was analyzed by χ2 test or Fisher's exact test. Three-year overall survivals of PNI positive and negative patients were determined using the Kaplan-Meier method. Detection results were compared using log-rank test. RESULTS: Of 372 colorectal cancer patients, 133 (35.8%) were PNI positive. Among the PNI positive patients, 63 cases were male and 70 cases female; 76 cases were more than 60 years old and 57 cases less than 60 years old; tumors of 6 cases located in the ileocecal colon, of 33 cases in the ascending colon, of 7 cases in the transverse colon, of 8 cases in the descending colon, of 22 cases in the sigmoid colon, and of 57 cases in the rectum; tumor diameter was greater than 4 cm in 83 cases, and less than 4 cm in 50 cases; tumors of 48 cases were moderately or highly differentiated, and of 85 cases poorly-differentiation; tumor invasion depth in 2 cases, T2 in 7 cases, T3 in 93 cases, T4 in 31 cases; lymphatic metastasis was N0 phase in 56 cases, N1 in 41 cases, and N2 in 36 cases; tumors were stage I( in 2 cases, stage II( in 40 cases, of stage III( in 75 cases and stage IIII( in 16 cases. The positive rate of PNI was significantly associated with tumor location (χ2=11.20, P=0.048), tumor size (χ2=21.80, P=0.000), differentiation (χ2=60.90, P=0.000), depth of invasion (χ2=19.00, P=0.000), lymph node metastasis (χ2=19.70, P=0.000) and TNM staging (χ2=70.80, P=0.000), but not with sex, age or vascular invasion(P>0.05). The median follow-up time was 48 (8 to 62) months. Kaplan-Meier survival curve showed that the 3-year survival rate of PNI positive patients was 52.6%, significantly lower than that of PNI negative patients(78.3%, P=0.000). Further analysis of patients with stage II( and III( colorectal cancer showed that the 3-year survival rates of PNI positive patients were 62.3% and 43.5%, respectively, which were significantly lower than those of PNI negative patients with stage II( and III((91.7% and 79.4%), and the differences were statistically significant(P=0.000). CONCLUSIONS: PNI is a poor prognostic factor of colorectal cancer. It may be a complement of the classic TNM staging classification in stratifying colorectal cancer patients, especially in stages II( and III(.

Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs. MATERIALS AND METHODS: The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared. RESULTS: Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS. CONCLUSION: NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.

Preoperative Multidetector CT Diagnosis of Extrapancreatic Perineural or Duodenal Invasion Is Associated with Reduced Postoperative Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma: Preliminary Experience and Implications for Patient Care.

Purpose To test the hypothesis that patients with pancreatic adenocarcinoma who otherwise are viewed to have resectable disease but have preoperative findings of extrapancreatic perineural invasion (EPNI) and/or duodenal invasion at multidetector computed tomography (CT) have reduced postoperative survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). Materials and Methods This study was approved by the institutional review board and complied with HIPAA. The authors retrospectively evaluated 76 consecutive patients with PDAC who underwent preoperative multidetector CT and subsequent pancreaticoduodenectomy. Two radiologists blinded to surgical pathology results and clinical outcome evaluated multidetector CT images for evidence of EPNI and duodenal invasion; discrepancies were resolved by consensus. Also determined for each patient were resected lymph node status, tumor size, surgical margin status, time to progression, and time to death. Data were assessed with the Goodman-Kruskal gamma for correlations among indicators and the log-rank test, Kaplan-Meier estimates, and multivariate Cox proportional hazards regression for survival analysis. Results In univariate analysis, duodenal invasion and/or EPNI on preoperativemultidetector CT images was associated with significantly decreased progression-free survival (P < .0001) and overall survival (P = .0013), and the clinical indicators (lymph node status, tumor size, and surgical margin status) as well as duodenal invasion and/or EPNI showed correlation with each other. In multivariate regression that included multidetector CT findings as well as the three traditional clinical indicators, only duodenal invasion and/or EPNI showed significant independent association with reduction in both modes of survival (P < .0001 and P = .014, respectively). Interobserver agreement was substantial with respect to EPNI and duodenal invasion (κ = 0.691 and 0.682, respectively). Conclusion Patients with evidence of EPNI and/or duodenal invasion on preoperative multidetector CT images have significantly reduced survival after pancreaticoduodenectomy for PDAC. © RSNA, 2016.

Chemically Induced Oncogenesis in the Peripheral Nervous System Is Suppressed in Congenic BDIX.BDIV-Mss1 and -Mss7 Rats.

Human malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas with a poor prognosis that arise either in the context of neurofibromatosis 1 or sporadically. Inbred BDIX and BDIV rat strains highly susceptible and resistant, respectively, to the development of ethylnitrosourea-induced MPNST enable us to identify, by using methods not applicable in humans, variant alleles involved in the pathways underlying individual MPNST risk. On the basis of a genome-wide association analysis using reciprocal intercrosses of BDIX and BDIV, BDIV alleles of two loci on chromosome 10, Mss1 and Mss7, were predicted to lower the risk of MPNST, the latter locus with a female bias. In this study we confirm the two nonoverlapping loci by exposing two congenic strains, BDIX.BDIV-Mss1 (Mss1) and BDIX.BDIV-Mss7 (Mss7), each carrying a BDIV genomic segment spanning the respective locus, to ethylnitrosourea. Compared with BDIX rats, the rate of MPNST is reduced 6.2-fold and 2.0-fold for Mss1 and Mss7 rats of both sexes, respectively. Although a moderate gain of survival time (30-50 days) is seen in Mss1 rats of both sexes and Mss7 males, Mss7 females survive 134 days longer than BDIX females. BDIV alleles at Mss7 obviously cause a markedly increased intrastrain sex difference regarding survival time in Mss7 compared with BDIX rats. Fine mapping will lead to the identification of allelic variants modulating rat MPNST risk and subsequently to their human counterparts. This is of particular relevance, because so far neither gene nor anonymous sequence variants have been identified that influence the risk of human sporadic Schwann cell malignancy.

Prognostic significance of MDM2 gene expression in childhood neuroblastoma.

AIM: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma. MATERIALS AND METHODS: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with -Q-PCR analysis in fresh tumor samples and FISH in FFPE samples. RESULTS: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan - Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization. CONCLUSION: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.

Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery.

BACKGROUND: The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: A total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied. RESULTS: At a median follow-up of 79.0 months (range 3-250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7% for grade 1, 63.8% for grade 2, 75.0% for grade 3, 90.4% for grade 3+, and 96.0%,for grade 4. The 10-year DFS was 31.8% for grade 1, 58.6% for grade 2, 70.4% for grade 3, 88.4% for grade 3+, and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS. CONCLUSIONS: The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.

BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.

Age-dependent prognostic effect by Mitosis-Karyorrhexis Index in neuroblastoma: a report from the Children's Oncology Group.

Prognostic effects of Mitosis-Karyorrhexis Index (MKI) used in the International Neuroblastoma Pathology Classification (INPC) are age-dependent. A total of 4,282 neuroblastomas reviewed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory (8/1/2001-3/31/2012) included 2,365 low-MKI (L-MKI), 1,068 intermediate-MKI (I-MKI), and 849 high-MKI (H-MKI) tumors. Cox proportional hazards models were fit to determine age cut-offs at which the relative risk of event/death was maximized in each MKI class. Backward-selected Cox models were fit to determine the prognostic strength of the age cut-offs for survival in the presence of other prognostic factors. The age cut-offs used in the INPC for L-MKI tumors (<60 months, n  =  2,710, 84.0% ± 1.0% event-free survival [EFS], 93.8 ± 0.7% overall survival [OS] vs ≥60 months, n  =  195, 49.8% ± 4.6% EFS, 71.7% ± 4.1% OS; P < 0.0001) and I-MKI tumors (<18 months, n  =  568, 83.8% ± 2% EFS, 93.7% ± 1.3% OS vs ≥18 months, n  =  500, 51.4% ± 2.9% EFS, 66.7% ± 2.7% OS; P < 0.0001) were within the effective range for distinguishing prognostic groups. As for H-MKI tumors (no cut-off age in the INPC, 51.0% ± 2.2% EFS, 64.4% ± 2.1% OS), a new cut-off of 3-4 months was suggested (<4 months, n  =  38, 82.3% ± 8.4% EFS, 81.8% ± 8.5% OS vs ≥4 months, n  =  811, 49.6% ± 2.2% EFS, 63.7% ± 2.1% OS, P  =  0.0034 and 0.0437, respectively). Multivariate analyses revealed that cut-offs of 60 and 18 months for L-MKI and I-MKI tumors, respectively, were independently prognostic. However, the cut-off of 4 months for H-MKI tumors did not reach statistical significance in the presence of other factors. The age cut-offs for MKI classes (60 months for L-MKI, 18 months for I-MKI, no cut-off for H-MKI) in the current INPC are reasonable and effective for distinguishing prognostic groups with increased risk of event/death for older patients.

Diagnostic approach, treatment, and outcomes of cervical sympathetic chain schwannomas: a global narrative review.

OBJECTIVE: This review examined the diagnostic approach, surgical treatment, and outcomes of cervical sympathetic chain schwannomas (CSCS) to guide clinical decision making. DATA SOURCES: Medline, EMBASE, and Cochrane databases. REVIEW METHODS: A literature review from 1998 to 2013 identified 156 articles of which 51 representing 89 CSCS cases were evaluated in detail. Demographic, clinical, and outcomes data were extracted by 2 independent reviewers with high interrater reliability (κ = .79). Cases were mostly international (82%), predominantly from Asia (50%) and Europe (27%). CONCLUSIONS: On average, patients were 42.6 years old (SD = 13.3) and had a neck mass ranging between 2 to 4 cm (52.7%) or >4 cm (43.2%). Nearly 70% of cases were asymptomatic at presentation. Presurgical diagnosis relied on CT (63.4%), MRI (59.8%), or both (19.5%), supplemented by cytology (33.7%), which was nearly always inconclusive (96.7%). US-treated cases were significantly more likely to receive presurgical MRI than internationally treated cases but less likely to have cytology (P < .05). Presurgical diagnosis was challenging, with only 11% confirmatory accuracy postsurgically. Irrespective of mass size, extracapsular resection (ie, complete resection with nerve sacrifice) was the most frequently (87.6%) performed surgical procedure. Common postsurgical adverse events included Horner's syndrome (91.1%), first bite syndrome (21.1%), or both (15.7%), with higher prevalence when mass size was >4 cm. Adverse events persisted in 82.3% of cases at an average 30.0 months (SD = 30.1) follow-up time. IMPLICATIONS FOR PRACTICE: Given the typical CSCS patient is young and asymptomatic and the likelihood of persistent morbidity is high with standard surgical approaches, less invasive treatment options warrant consideration.

Disease-specific outcomes of radical prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time.

BACKGROUND: Prostate cancer is the most common male malignancy and a mayor cause of mortality in the western world. The impact of clinicopathological variables on disease related outcomes have mainly been reported from a few large US series, most of them not reporting on perineural infiltration. We therefore wanted to investigate relevant cancer outcomes in patients undergoing radical prostatectomy in two Norwegian health regions with an emphasis on the impact of perineural infiltration (PNI) and prostate specific antigen- doubling time (PSA-DT). METHODS: We conducted a retrospective analysis of 535 prostatectomy patients at three hospitals between 1995 and 2005 estimating biochemical failure- (BFFS), clinical failure- (CFFS) and prostate cancer death-free survival (PCDFS) with the Kaplan-Meier method. We investigated clinicopathological factors influencing risk of events using cox proportional hazard regression. RESULTS: After a median follow-up of 89 months, 170 patients (32%) experienced biochemical failure (BF), 36 (7%) experienced clinical failure and 15 (3%) had died of prostate cancer. pT-Stage (p = 0.001), preoperative PSA (p = 0.047), Gleason Score (p = 0.032), non-apical positive surgical margins (PSM) (p = 0.003) and apical PSM (p = 0.031) were all independently associated to BFFS. Gleason score (p = 0.019), PNI (p = 0.012) and non-apical PSM (p = 0.002) were all independently associated to CFFS while only PNI (P = 0.047) and subgroups of Gleason score were independently associated to PCDFS. After BF, patients with a shorter PSA-DT had independent and significant worse event-free survivals than patients with PSA-DT > 15 months (PSA-DT = 3-9 months, CFFS HR = 6.44, p < 0.001, PCDFS HR = 13.7, p = 0.020; PSA-DT < 3 months, CFFS HR = 11.2, p < 0.001, PCDFS HR = 27.5, p = 0.006). CONCLUSIONS: After prostatectomy, CFFS and PCDFS are variable, but both are strongly associated to Gleason score and PNI. In patients with BF, PSA-DT was most strongly associated to CF and PCD. Our study adds weight to the importance of PSA-DT and re-launches PNI as a strong prognosticator for clinically relevant endpoints.

Malignant peripheral nerve sheath tumors of the spine: a SEER database analysis.

Peripheral nerve sheath tumors are uncommon neoplasms that can affect any area of the body. Spinal lesions, especially those that are malignant, pose difficult management challenges, and data regarding these lesions are limited by the disease rarity. This study provides a population-based analysis using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patient characteristics and treatments. Surgery is associated with improved survival, whereas radiation therapy is associated with decreased survival in this cohort with malignant peripheral nerve sheath tumor in the spine.

Surgery for primary filum terminale ependymomas: outcome and prognostic factors.

INTRODUCTION: Primary filum terminale ependymoma (PFTE) is a unique type of ependymomas and locates on extramedullary site. However, the clinical features and prognostic factors of PFTE are still unknown due to its rarity. AIM: This study aimed to evaluate the clinical features, outcomes, and prognostic factors of PFTE in the largest series of cases. RESULT: Thirty-eight patients were included in this study. Gross total removal (GTR) of the tumors was achieved in 33(87%) patients. Five (13%) patients had subtotal resection (STR). For the residual tumors, postoperative radiotherapy increased the interval between the first surgery and tumor regrowth (P = 0.063). Six patients had local recurrence/progression. Univariate analysis identified STR(P = 0.001), unencapsulated tumor (P = 0.018), tumor involving more than two vertebral columns (P = 0.005), and tumor invading sacral canal(P < 0.001) as predictors of tumor recurrence. In addition, 36 (95%) patients had stable or improved neurological status directly after surgery. Klekamp-Samii score was better correlated with the symptoms than McCormick scale. CONCLUSION: Extent of surgical removal, tumor size, tumor location, and the integrity of tumor capsule are the prognostic factors of PFTEs, and the intrasacral PFTEs always have a poor prognosis.

GLUT1 protein expression correlates with unfavourable histologic category and high risk in patients with neuroblastic tumours.

GLUT1 is a hypoxia-induced gene that has many biologically important functions, and the overexpression of the GLUT1 protein correlates with poor prognosis in several adult cancers. The clinical significance of the GLUT1 protein in peripheral neuroblastic tumours (NTs) has not been comprehensively documented. In the present retrospective study, immunohistochemical analyses revealed the presence of GLUT1 in 44/96 (46 %) NTs. Membranous GLUT1 was present in neuroblasts of 44/87 neuroblastomas (NBs) and nodular ganglioneuroblastomas (nGNBs) but was absent in ganglion cells. The presence of GLUT1 was significantly increased in NBs and nGNBs compared with maturing ganglioneuromas and intermixed ganglioneuroblastomas (P < 0.001). The proportion of NBs and nGNBs expressing GLUT1 was significantly increased in the high-risk and low/intermediate-risk groups compared with the very-low-risk group (P = 0.022) and the unfavourable compared with the favourable pathology prognostic group (P = 0.027). In the Cox regression analyses, GLUT1 expression indicated a worse overall survival (OS; hazard rate ratio (HR) 2.29, P = 0.053) and event-free survival (EFS; HR 1.68, P = 0.181) which was not attenuated by adjustment for the mitosis-karyorrhexis index and MYCN amplification (OS: adjusted HR 2.44, P = 0.053 and EFS: adjusted HR 1.63, P = 0.244). This indicated that GLUT1 protein expression was independent of mitosis-karyorrhexis index and MYCN amplification as a prognostic factor. Our data may have clinical significance because GLUT1 was also present in a higher proportion of high-risk NTs.

VEGF-C, VEGF-D and VEGFR-3 expression in peripheral neuroblastic tumours.

AIMS: More than 50% of neuroblastomas (NBs) present with haematogenous and/or lymphatic metastasis; however, little is known about the clinicopathological significance in NBs of the key lymphangiogenesis growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D and the receptor VEGFR-3. METHODS AND RESULTS: Ninety-three NBs and nine ganglioneuromas (GNs) were immunostained for VEGF-C, VEGF-D and VEGFR-3. VEGF-C and VEGF-D were present in 76% and 82% of the NBs, respectively. There was no significant difference in VEGF-C expression between NBs and GNs. VEGF-D expression was significantly higher in NBs compared with GNs and in MYCN-amplified NBs. VEGFR-3 tumoral cell expression (VEGFR-3c), present in 48% of the NBs, was significantly higher in NBs from children ≥ 18 months at presentation and those belonging to a high-risk group. VEGFR-3 lymphovascular density was increased significantly in NBs compared with GNs and in NBs associated with adverse clinicopathological and biological factors. Lymphovascular invasion, assessed in VEGFR-3-stained vessels, was present in ∼50% of NBs. Cox regression analyses demonstrated that VEGFR-3c expression was associated with a significantly shorter event-free survival and that its effect was independent of the important pathological variable, mitosis-karyorrhexis index. CONCLUSIONS: VEGF-D and VEGFR-3 up-regulation support tumour progression in NB and VEGFR-3c may provide a useful prognostic marker in NBs.

A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: histologic subcategories and patient outcomes.

OBJECTIVE: The aims of this study were to define a novel classification system of tumor perineural invasion (PNI) with respect to tumor/nerve involvement such as intratumoral (IT), peripheral, or extratumoral (ET) and to determine the prognostic significance of each of these histologic subcategories in patients with noncutaneous head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: This study is a retrospective chart review and histologic analysis of patients with HNSCC in the setting of a tertiary care medical center. METHODS: A clinical chart review of 142 patients with HNSCC who underwent primary surgical treatment from January 2004 through December 2007 was performed. Clinical information collected included patient age, sex, alcohol and tobacco use, tumor location, TNM stage, postoperative adjuvant chemotherapy and/or radiation treatment, and patient outcome. For each case, PNI density, the distance of each PNI focus to the tumor edge, and size of the largest nerve involved were measured. Furthermore, PNI was subcategorized as IT, peripheral, or ET. A Cox regression analysis was performed to determine if PNI was related to regional disease recurrence. Kaplan-Meier survival analysis was also performed. RESULTS: Among the 142 patients, 37 (26%) had disease progression. The maximum extent of PNI was significantly correlated with disease-free survival on multivariate analysis (P = .019) and was also significantly related to disease-free survival when T stage (P = .017), N stage (P = .021), and T and N stages (P = .02) were added to the Cox regression model. Kaplan-Meier analysis demonstrated a trend toward increased disease-free survival of PNI negative and IT/peripheral PNI compared with ET PNI. CONCLUSION: Perineural invasion is correlated with nodal status and T stage and is related to disease-free survival. It can be subcategorized as IT, peripheral, or ET. This novel classification system has important implications with regard to clinical outcome and may help define a cohort of patients that may require more aggressive management.

Surgical treatment of rare cauda equina tumours.

BACKGROUND: Cauda equina tumours (CET) are rare and usually benign. Treatment of schwannomas and benign ependymomas, which are the most frequent histopathological types of CET, is now well established. However, management of other presumed histopathological types of CET is still a matter of debate. The aim of this study was to assess the incidence and the surgical treatment of rare CET. METHOD: A retrospective study was carried out on 176 adult patients surgically treated for CET in our two departments from 1994 to 2010. We reviewed pre- and postoperative symptoms, magnetic resonance imaging aspects, surgical findings, outcome including operative neurological morbidity, local recurrence rate and operative mortality, and incidence of rare CET. FINDINGS: Seventeen percent (30 patients) of CETs operated on were neither schwannomas nor benign ependymomas. Half of these cases were benign tumours, with paragangliomas being the most common. Two patients were in poorer clinical condition after surgery, one patient experienced a local recurrence, and one died following surgery, from the progress of his disease (Von Hippel-Lindau disease). The other half were malignant tumours, with metastases being the most common. One third of the patients were worsened by surgery, and the mortality rate was 1/3 at 8 months (1-27 months). CONCLUSIONS: Roughly one in six CET were neither schwannomas nor benign ependymomas. This study demonstrated the efficiency of surgery for rare benign CET with a low local recurrence rate. Surgical treatment of rare malignant CET led to a high rate of increased postoperative neurological deficit in patients with a reduced life expectancy.

Perineural invasion after preoperative chemotherapy predicts poor survival in patients with locally advanced gastric cancer: gene expression analysis with pathologic validation.

BACKGROUND: We examined gene expression profiles and clinicopathologic features (tumor location, stage, graded pathologic response, perineural invasion (PNI), Lauren's classification, and survival) of patients with gastric cancer who received preoperative chemotherapy to identify prognostic markers. METHODS: Thirty-eight patients with locally advanced gastric cancer received preoperative chemotherapy on a phase II trial. Twelve fresh-frozen tumor samples were available for RNA expression analysis. Differential gene expression between tumors with and without PNI was identified and correlated with clinicopathologic features. RESULTS: Preliminary hierarchical clustering suggested a separation between long- and short-term survivors. The close association between PNI and overall survival was identified and validated immunohistochemically in 31 completely resected gastric tumors. Five-year survival for patients with PNI and without PNI was 5% and 65%, respectively (P < 0.01). PNI added significant prognostic value to posttreatment pathologic stage, (P < 0.01). Differential gene expression profile for PNI and non-PNI tumors identified 111 potentially relevant genes. CONCLUSIONS: Our results demonstrate that the presence of PNI after preoperative chemotherapy is associated with poor survival. These results need to be validated in prospective studies, to help establish whether patients with evidence of PNI would be candidates for more aggressive therapy or enrollment into clinical trials. The presence of PNI provides additional prognostic importance to posttreatment pathologic stage and may indicate treatment resistance. Understanding the molecular events associated with PNI, may provide insight into new therapeutic agents for this subset of patients with resistant tumors.

The effect of perineural invasion on overall survival in patients with gastric carcinoma.

AIMS: The availability of different treatment options for gastric carcinoma has reopened the question of correct definition of high-risk categories, which may help in identifying patients with high risk for poor prognosis who would benefit more from adjuvant therapy after operation. Perineural invasion (PNI) seems to provide useful information for management. Therefore, we examined the effect of PNI on overall survival (OS) in patients with gastric carcinoma and the association between PNI and other clinical and pathological factors. PATIENTS AND METHODS: A total of 1,632 patients with gastric carcinoma from 2000 to 2005 were analyzed retrospectively. Paraffin sections of surgical specimens from all patients who underwent gastric resection were stained with laminin. If carcinoma cells infiltrated into the perineurium or neural fascicles, PNI was assessed as positive. Survival analysis was done in 1,372 patients with T1-T4 tumors who underwent curative resection. RESULT: PNI was positive in 518 of the 1,632 patients (31.7%). The size of tumors, T stage, differentiation of tumor, and clinical stage were significantly related to PNI positivity. The proportion of large tumors was significantly higher in PNI-positive patients than in PNI-negative patients (P < 0.01). As the depth of gastric mural invasion or clinical stage increased, the positive rate of PNI also increased. The OS of the PNI-positive patients was significantly shorter than that of the PNI-negative patients in the univariate analysis (P < 0.01). At multivariate Cox proportional hazards model of OS analysis, the positivity of PNI appeared to be an independent prognostic factor for OS (hazards ratio [HR] = 3.23, 95%CI = 2.6-8.11, P < 0.01), which was also influenced by tumor differentiation, T stage, and clinical stage (P < 0.01). CONCLUSION: Our results suggested that the incidence of PNI was high in gastric carcinoma and that it corresponded to the progression of disease. It could provide additional information for identifying patients who are at high risk for poor prognosis. PNI can be a candidate for a new kind of prognostic parameters.