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.

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.

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.

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.

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.

Morphometric evaluation of NB84, synaptophysin and AgNOR is useful for the histological diagnosis and prognosis in peripheral neuroblastic tumors (pNTs).

OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) and synaptophysin (p=0.01) reached statistical significance as prognostic indicators. CONCLUSIONS: Determination of NB84 and synaptophysin are useful tools for the diagnosis of peripheral neuroblastic tumors The association of the evaluation of AgNOR expression by the tumor cells may provide an important contribution to the prognostic evaluation and management approach of the patients.

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.

[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(.

Prognostic value of the International Neuroblastoma Pathology Classification in Neuroblastoma (Schwannian stroma-poor) and comparison with other prognostic factors: a study of 182 cases from the Spanish Neuroblastoma Registry.

In addition to clinical and biological factors, further valuable prognostic information in neuroblastoma (Schwannian stroma-poor) (NB) patients is provided by the histopathologic analysis and the application of the International Neuroblastoma Pathology Classification (INPC) system. The objective of this study was to assess the prognostic impact of the INPC classification in a series of NB (Schwannian stroma-poor) and its relation with other prognostic factors. One hundred eighty-two cases of NB were collected from the files of the Spanish Neuroblastoma Registry. Slides were reviewed, and NB cases were grouped into favorable and unfavorable categories according to INPC criteria, taking into account morphological features (mitosis-karyorrhexis index, histological subtype) and patient's age at diagnosis. Other pathological [presence of calcifications, tissular components, and number of mitotic cells per 10 high-power field (HPF)], immunohistochemical (P-glycoprotein and Ki-67 protein expression) and genetic (MYCN amplification and chromosome 1p deletion) features were also studied. Statistical analyses of overall survival with Kaplan-Meier curves and a multivariate study using Cox regression were performed (40.3% of NBs were considered favorable and 59.7% unfavorable). Unfavorable NB showed a mean survival time of 57 months compared with 89 months in favorable cases. Advanced stage, more than ten mitoses per 10 HPF, Ki-67 expression in more than 30% of tumor cells, MYCN oncogene amplification and chromosome 1p deletion were observed more frequently in unfavorable NB. The Cox regression analysis demonstrated that clinical stage (International Neuroblastoma Staging System stage 4) and histological subtype (undifferentiated NB) were the most important factors that influence the overall survival (p<0.001). INPC classification results are major prognostic indicators in NB and should be considered in the therapeutic stratification of NB patients.

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.

Malignant peripheral nerve sheath tumors (malignant schwannomas) in children.

We studied the clinical and pathologic features of 78 malignant peripheral nerve sheath tumors in children less than or equal to 15 years of age. There were 42 boys and 36 girls, with a median age of 10 years. The majority of the tumors (42, or 54%) were central or axial in location; the rest were peripheral. Sixteen patients (21%) had a history of von Recklinghausen's disease. Fourteen (18%) had a malignant peripheral nerve sheath tumor arising in a nerve trunk or a neurofibroma and were unassociated with von Recklinghausen's disease. Patients typically presented with a painful mass of variable duration. Tumors ranged from 2 to 33 cm (median, 7.5 cm) and demonstrated a wide histologic spectrum that included spindled, epithelioid, and primitive neuroepithelial-like cells as well as heterologous elements (11). Immunohistochemical staining revealed S-100 protein in 28 of 50 cases (56%) as well as vimentin (13 of 21 cases, or 62%), Leu 7 (22 of 49 cases, or 45%), actin (eight of 20 cases, or 40%), and keratin (seven of 27 cases, or 26%). Survival status was known for 57 patients (73%). Kaplan-Meier estimates revealed a median survival of 45 months. Half of the patients had local recurrences at 12 months, and half had metastases at 24 months, most commonly to lungs, followed by lymph nodes, liver, bone, soft tissue, and brain. Age greater than or equal to 7 years, male sex, presence of von Recklinghausen's disease, central location, larger tumor size, and tumors with greater than or equal to 25% necrosis were found to be potentially significant adverse prognostic indicators by univariate analysis. Multivariate analysis revealed that larger tumor size, age greater than or equal to 7 years, tumor necrosis greater than or equal to 25%, and von Recklinghausen's disease to be independent adverse prognostic factors.

Acoustic neuroma and the suboccipital approach (1967-1972).

The goal of successful acoustic tumor surgery is to totally remove the tumor and preserve neurologic function. This paper reviews 132 patients, with particular emphasis on the hospital mortality rate, total removal of the neoplasm, and preservation of facial function and, in 3 instances, hearing.

Prognostic significance of the diameter of perineural invasion in radical prostatectomy specimens.

We assessed whether the quantification of cancer invasion into the perineural space influences the prognosis of patients treated with radical prostatectomy. We conducted a retrospective study of clinical and pathologic features in 640 consecutive patients with clinical stage Tla-T3bNXM0 prostate cancer who were treated with radical retropubic prostatectomy by the same surgeon between 1989 and 1995. None had received preoperative hormonal therapy or radiotherapy. Detailed pathologic analysis, including the presence and maximum diameter of perineural invasion (PNI), was performed by 2 pathologists. Treatment failure was defined as either a serum prostate-specific antigen (PSA) level > 0.4 ng/mL and rising or initiation of adjuvant therapy. The median follow-up time was 48 months (range, 1 to 111 months). Overall, PNI was detected in 477 patients (75%). The progression-free 5-year probability rate after prostatectomy for patients with PNI was 70% +/- 3% compared with 94% +/- 2% for patients without PNI (P <.001). The mere presence of PNI was not an independent predictor of progression in a Cox proportional hazards analysis when the other established prognostic factors (serum PSA level, pathologic stage, surgical margin, and tumor volume) were considered. However, the increasing diameter of the largest focus of PNI was strongly associated with other established prognostic factors and the probability of progression after radical prostatectomy. Although little adverse effect in patients with PNI < 0.25 mm was seen 5 years after surgery, those with a PNI diameter of 0.25 to 0.5 mm were significantly (P <.001) less likely to remain free of progression; only 36% of those with PNI of 0.5 to 0.75 mm (P <.001) and 14% of those with PNI > or =0.75 mm (P =.002) were free of progression. In a Cox proportional hazard analysis, the PNI diameter was an independent predictor of prognosis. These results support that the measurement of the PNI diameter, easily recorded from prostatectomy specimens, could add important information to the prognosis of prostate cancer patients. Controversy regarding the significance of PNI may result from the lack of quantitative assessment of PNI in previous studies.

Ependymoma of the cauda equina region: diagnosis, treatment, and outcome in 15 patients.

New diagnostic imaging techniques make possible a reappraisal of current diagnostic, therapeutic, and management strategies for certain rare lesions of the central nervous system. With this in mind, we have reviewed our experience with ependymoma of the filum terminale and cauda equina region. Fifteen patients with this tumor have been treated since 1955. Typical presentations included pain, lower extremity weakness, and, occasionally, bladder dysfunction. Delays in arriving at the proper diagnosis have been the rule; however, we have noted a substantial increase in the number of these tumors referred to us since the advent of magnetic resonance imaging. Treatment includes surgical resection to the extent consistent with preservation of neurological function; postoperative irradiation appears to be of benefit in controlling recurrence except in those patients whose well-circumscribed tumors have been removed completely. Presence of urinary difficulties at the time of diagnosis is a relatively poor prognostic sign, and a more liberal use of magnetic resonance imaging in cases of persistent or recurrent low back and radicular pain unresponsive to conservative therapy may help to achieve earlier diagnosis. Because of the possibility of late recurrence, prolonged follow-up is mandatory for all patients, and magnetic resonance imaging is the diagnostic tool of choice.

Prognostic evaluation of perineural invasion in rectal cancer.

To evaluate whether perineural invasion (PNI) is an important prognostic factor in patients with rectal cancer, we reviewed the records of 373 patients who underwent curative surgery. Thirty-seven patients (9.9%) were identified as having tumors with PNI. The incidence of PNI was significantly increased in lesions categorized as stage III by the International Union Against Cancer (UICC) system (20%). There was a significant difference in local recurrence between patients with stage III lesions with PNI and those with stage III lesions without PNI (p < 0.005). Also, patients with PNI of stage III lesions had a significantly lower 8-year survival rate (26.7%, p < 0.001). We conclude that PNI is an important factor influencing the prognosis of patients with stage III disease. PNI should be classified as a subgroup of the clinical stage.

Ependymomas: a clinical and pathologic study. Part II. Survival features.

A survival analysis of cases of ependymoma was performed. Patients with ependymomas of the infratentorium were found to have shorter disease-free intervals and to live for a shorter time after treatment than those with tumors of the cauda equina. Children with infratentorial tumors did not have a recurrence if they survived 3 or more years after operation, whereas adults with infratentorial tumors could have a first recurrence even 5 or more years after surgery. Younger patients did not survive as long as older patients in the group of infratentorial ependymomas. In contrast, age did not influence survival in patients with cauda equina ependymomas. Patients with ependymomas of the infratentorium and the cauda equina having long histories had a better prognosis than those with short histories. Changes in mitotic index and tumor cell number could not be correlated with the length of survival. In the infratentorial group, patients with rosette-bearing tumors had a poor prognosis, whereas patients with subependymal areas in their tumor had a better prognosis. Total surgical removal with no further treatment appeared to be as effective as subtotal removal followed by radiotherapy for the cauda equina tumors.

Mediastinal tumors of peripheral nervous system origin.

A wide spectrum of benign and malignant tumors of peripheral nervous system origin can arise in the mediastinum. These neoplasms are more frequent in the posterior mediastinum and can develop from peripheral nerves, sympathetic and parasympathetic ganglia, and neural tube embryonic remnants. The clinicopathologic features of mediastinal schwannomas, melanotic schwannomas, neurofibromas, ganglioneuromas, granular cell tumors, malignant tumors of peripheral nerve sheath origin, malignant melanocytic tumors of peripheral nerve sheath origin, neuroblastomas, ganglioneuroblastomas, and pigmented neuroectodermal tumors of infancy are reviewed.