The significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

Summary

Recently, neoadjuvant therapy for locally advanced rectal cancer has been generally performed. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and the survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. A total of 64 patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TILs subsets was examined using immunohistochemical staining of pretreatment biopsy samples and posttreatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8⁺ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8⁺ TILs in posttreatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort the density of CD8⁺ TILs in posttreatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples may be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, may induce the activation of the local immune status.

This article is protected by copyright. All rights reserved.

http://ift.tt/2omjFfT

Epilepsy with auditory features: Long-term outcome and predictors of terminal remission

Summary

Objective

To assess the long-term outcome of epilepsy with auditory features (EAF) and to identify the clinical predictors for prognosis.

Methods

The study involved consecutive EAF patients with a follow-up of ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimate to calculate the cumulative time-dependent probability of conversion to TR. Log-rank test and multivariate Cox regression analyses were performed to study the association between time to TR and prognostic determinants.

Results

We included 123 EAF patients (male/female = 58/65) with a median follow-up of 11 years (1626.9 person-years). Most were sporadic cases (68.3%), whereas 31.7% reported a family history of epilepsy. At last assessment, 42 patients had achieved TR (34.1%). Of the remaining 81 cases with no TR (65.9%), 37% had been in remission for 1-4 years and 62.9% still had seizures within the past year. The cumulative rates of TR were 26.6%, 35.7%, and 51.6% at 10, 20, and 30 years from inclusion. On multivariate analysis, age at onset > 10 years (hazard ratio [HR] = 3.2, P = .028), auditory aura characterized by distortions only versus simple/complex hallucinations (HR = 2.9, P = .041), and unremarkable scalp electroencephalogram (EEG) versus EEG with focal epileptiform activity (HR = 3.5, P = .041) were associated with TR.

Significance

Our data show a wide prognostic spectrum of EAF, ranging from mild forms with spontaneous remission, to severely refractory epilepsy addressed to surgery. The outcome, less favorable than expected from previous studies, appears to be primarily a function of 3 prognostic negative risk factors: age at onset < 10 years, auditory aura characterized by complex auditory hallucinations, and focal epileptiform abnormalities on scalp EEG. These predictors, easy to collect even at the first visit, may inform both clinicians and patients about the long-term prognosis and aid patient management.

http://ift.tt/2BIvkxW

Basal Cell Carcinoma Induced by Therapeutic Radiation for Tinea Capitis – Clinical Pathological Study

Abstract

Aims

An increased prevalence of aggressive histological subtypes, such as the micronodular and morpheaform, has been seen, irrespective of the clinical course, in basal cell carcinoma (BCC) following irradiation for tinea capitis. The aim of this study was to assess the histopathological features of BCCs among patients irradiated for tinea capitis and correlate them with the clinical course.

Methods and Results

The medical records and BCC biopsy specimens of individuals who were previously irradiated for tinea capitis were revised. Demographic data and clinical characteristics were retrieved. Biopsy specimens were evaluated for histological subtype classification and additional histopathological features. A telephone survey was conducted to assess the clinical behaviour of the tumours. Thirty-one patients (17 male, 14 female) were included. The average age at time of first biopsy was 56 years. The total number of lesions was 185, with 80% of subjects showing multiple lesions. Nodular subtype was the most prevalent, followed by superficial, micronodular, and mixed tumours. Third of the BCC could be classified as aggressive histologically. Stromal fibroplasia and melanin deposits were common. There was no mortality related to BCC. None of the 17 patients who completed the survey had evidence of local invasiveness or metastases.

Conclusions

BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BHij7N

Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease

Abstract

Aims

Needle biopsy remains essential for diagnosis in assessment of liver disease, although there remains associated risk. Examination is largely limited to subjective evaluation and biopsies are not exploited to provide personalised prognostic information. Elastin is a durable component of fibrotic matrix in chronic disease, conferring resistance to remodelling and potentially influencing tissue biomechanics linked to portal hypertension. We hypothesised that elastin content was predictive of clinical outcome and so could be quantified to increase the beneficial information yield from a liver biopsy.

Methods and results

Elastin content in liver biopsies was determined by image analysis, technically validated in an independent centre, and correlated with outcome in patients with advanced (Ishak stage ≥ 5) chronic hepatitis C virus-related chronic liver disease. Elastin was robustly quantified in an operator- and laboratory-independent manner, with very strong correlation of elastin staining measured by two methods of image classification (r_s = 0.873, p < 0.00001). Elastin content (but not absolute scar content or Ishak stage) was predictive for future clinical outcomes. In a cohort of patients without sustained virologic response, median hepatic elastin content was 3.4%, and 17 patients (57%) progressed to a liver-related clinical outcome; 11 of the 15 patients (73%) with hepatic elastin >3.4% progressed to a clinical outcome, compared to only 6 out of 15 (40%) with elastin <3.4%. The difference in time to outcome was significant.

Conclusions

We describe a simple and reproducible method for elastin quantification in liver biopsies that provides potentially valuable prognostic information to inform clinical management.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oeX9WU

Grade 4 asbestosis does not extend directly from the respiratory bronchiole to the peripheral lung

Abstract

Aim

To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung.

Methods and results

We retrospectively examined the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1, and ≥ grade 2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI); and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grade 0, 1, or ≥2 lesions respectively, with mean respective numbers of ABs in dissolved lung of 117,000/g dry lung, 468,000/g, and 968,000/g; and in specimens on glass slides of 7 ABs/cm² of tissue slice, 34 ABs /cm², and 195 ABs /cm². The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively; with mean respective numbers of ABs in dissolved lung of 1,006,000/g dry lung and 354,000/g, and 186 and 56 ABs/cm² on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas, and UIP patterns originated in subpleural, peripheral lobules.

Conclusions

Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2opOqRc

Primary perianal adenocarcinoma of intestinal type – a new proposed entity

Abstract

Aims

The currently recognised subtypes of anal canal/perianal adenocarcinoma are those arising from low rectal mucosa or columnar cuff, fistula-related tumours and anal gland carcinoma. This following report presents two examples of a hitherto undescribed subtype of perianal adenocarcinoma with an intestinal phenotype.

Methods and Results

A 74 year old man had a perianal tumour locally excised whereas a 73 year old female underwent an abdominoperineal resection for perianal Paget's disease with an underlying carcinoma. Neither patient had a history of perineal fistulae, Crohn's disease or previous gastrointestinal neoplasia, and neither showed clinical, radiological or endoscopic evidence of another abdominal or pelvic tumour. Both resection specimens contained adenocarcinoma which were similar in demonstrating an intestinal morphology and CDX2 immunopositivity. The man has shown a disease-free outcome thus far but the woman has suffered with nodal and pelvic recurrence within a few months of surgery.

Conclusions

The name 'primary perianal adenocarcinoma of intestinal type' is proposed for this previously unrecognised subtype of perineal neoplasia. Awareness of its distinct existence – by recognising its intestinal morphology and immunophenotype while excluding metastasis from the intestinal tract – should help collate data to determine its specific prognosis and to formulate its best management.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ofe6Rc

A Genomic and Clinicopathologic Study of Non–Small Cell Lung Cancers with Discordant ROS1 Gene Status by Fluorescent In Situ Hybridization and Immunohistochemical Analysis

Abstract

Background

ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non–small cell lung cancer (NSCLC) slated for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescent in situ hybridization (FISH). The present study investigated the driver mutation and clinicopathologic characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases.

Patients and Methods

Tumors from 26 discordant cases were analyzed for clinicopathologic characteristics, mutations in EGFR, KRAS, ERBB2, BRAF, and PIK3CA; fusions in ALK and RET; and amplifications in MET, ERBB2, and ROS1.

Results

ROS1-rearranged NSCLCs were significantly more likely to be found in younger patients and at an advanced stage; they showed cribriform features, extracellular mucus, and psammoma bodies, whereas ROS1-discordant cases were found in older patients at a relatively early TNM stage and showed a lepidic growth pattern (all P <.001). Most of ROS1-rearranged NSCLCs were no concurrent mutation, whereas 73% of discordant cases harbored genetic aberrations, including EGFR and ERBB2. Compared with general lung adenocarcinomas, ERBB-2 abnormality was disproportionately high in ROS1-discordant cases. Moreover, we optimized the scoring criteria for ROS1 IHC as "H score >150 and no concurrent mutations"; then the specificity was increased to 81.6%.

Conclusions

Compared with ROS1-rearranged cases, ROS1-discordant patients showed distinct clinical and morphologic features and often harbored another oncogenic driver alteration. The use of optimized screening criteria will increase the specificity of ROS1 antibody.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BGd9IX