[Show abstract][Hide abstract] ABSTRACT: Postoperative chemotherapy is recommended for all patients with lymph node positive colon cancer. In colon cancer, mutations in the TP53 gene are present in more than 30% of tumors. We found that the most commonly used postoperative chemotherapy resulted in a marked survival benefit for patients with normal TP53 status while it was associated with significant survival disadvantage in TP53 mutant patients. Overall the survival disadvantage of the mutated patients almost balanced the survival benefit of the TP53 normal patients. This might be an explanation why chemotherapy resulted in less progress in survival of colon cancer than we would have expected.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to assess the clinicopathological significance of tumour differentiation of metastatic lymph node tissue in patients with American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III colorectal cancer. In a cohort of 145 patients, lymph node grades were G1 in 77 (53.1%), G2 in 41 (28.3%) and G3 in 27 (18.6%) cases, respectively. Despite differences in 77 (53.1%) cases, primary tumour and lymph node grade correlated significantly (Somer's D=0.639; p<0.001). Lymph node grade was significantly associated with N classification (p=0.009), tumour size (p=0.024) and lymphovascular invasion (p=0.004). Patients with lymph node grade G1 had better progression-free survival (p=0.031) and cancer-specific survival (p=0.008). Multivariable analysis identified lymph node grade as independent predictor of cancer-specific survival in this cohort. In conclusion, lymph node grade emerged as a promising novel prognostic variable for patients with AJCC/UICC stage III disease. Additional studies are warranted to validate this new finding.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: HintergrundDas Management von „kleinen Polypen“ im distalen Kolon und Rektum ist in den Fokus der Kosten-Nutzen-Analyse der Vorsorgekoloskopie geraten. So wird insbesondere im angloamerikanischen Sprachraum aktuell diskutiert, winzige (Die Amerikanische Gesellschaft für Gastroenterologische Endoskopie (ASGE) hat im Rahmen ihrer sog. Innovationsdiskussion („Preservation and Incorporation of Valuable Endoscopic Innovations [PIVI]“) diskutiert, Polypen unter 0,5 cm Durchmesser zwar zu entfernen, nicht jedoch histopathologisch zu untersuchen - um angeblich Kosten zu sparen (www. http://www.asge.org/publications/). In Computermodellrechnungen wurde ermittelt, dass durch das „Entfernen und Verwerfen“ pro Vorsorgekoloskopie 25 US-Dollar gespart werden könnten [1, 2].Nicht nur aus berufspolitischen Gründen wird die Diskussion auch in Deutschland geführt - und von einigen be ...
Der Pathologe 03/2015; 36(2). DOI:10.1007/s00292-015-0003-5 · 0.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This chapter explains the terminology and classification of colorectal neoplastic precursor lesions, with focus on serrated lesions: hyperplastic polyp, sessile serrated adenoma/polyp (or lesion), mixed polyp and traditional serrated adenoma. We refer to practical issues, such as the measurement of polyp size and the grading of intraepithelial neoplasia/dysplasia (low grade vs. high grade). The definition of invasion is driven by the World Health Organization and defined as invasion into the submucosal layer. Risk assessment of pT1 colorectal cancers is the prerequisite of clinical decision making ranging from follow-up only to additional endoscopic and surgical procedures. The evaluation is based upon the following parameters: depth of invasion (for sessile lesions reported according to Kikuchi levels sm1–sm3; for polypoid/pedunculated lesions reported according to Haggitt levels I–IV), tumour grade, vascular invasion, margin involvement, budding (tumour cell dissociation at the invasion front) and (possibly) perineural invasion.
[Show abstract][Hide abstract] ABSTRACT: Surgical resection is the treatment of choice for patients with locally confined disease, but early cancers may be adequately treated by endoscopic resection alone. In advanced colorectal cancers, accurate staging including pathological lymph node assessment is crucial for patient counselling and decision making. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the cancer specimen lymph node recovery is related to the actual number of regional lymph nodes that is related to patient demographics, tumor location and biology. Current guidelines recommend a minimum of twelve nodes harvested as the standard of care. In patients with node-negative tumors a variety of histological features may be used for adjusted risk assessment, including histological subtyping, lymphatic and venous invasion, tumor budding and tumor necrosis as well as the anti-tumor host inflammatory response which has been identified as favorable feature in several studies. In rectal cancer, involvement of the circumferential resection margin and the plane of surgery are important prognostic factors. Early or superficial colorectal cancer is defined as invasive adenocarcinoma invading into, but not beyond the submucosa. A number of features require special attention because they are used to determine the necessity for radical surgery. In addition to the assessment of completeness of excision, these include the recording of parameters that predict the presence of lymph node metastasis, namely the depth of invasion into the submucosa, tumor grade, and the presence of additional risk factors, such as angioinvasion and tumor budding. The combination of these parameters allows the stratification of affected individuals into low-risk and high-risk categories.Keywords: colorectal cancer - early colorectal cancer - lymph node metastasis - pathological features - risk factors - prognosis.
[Show abstract][Hide abstract] ABSTRACT: The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.158.
Modern Pathology 11/2014; 28(5). DOI:10.1038/modpathol.2014.158 · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microscopic colitis has emerged as a major cause of chronic watery non-bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathologic phenotypes and no significant endoscopic abnormalities: Lymphocytic colitis is defined by an increased number of surface intraepithelial lymphocytes, collagenous colitis by a thickened collagen band underneath the surface epithelium. There is increased inflammation in the lamina propria, but only little or no crypt architectural distortion. Incomplete and variant forms showing less characteristic features have been reported under different names. Differential diagnosis mainly includes resolving infectious colitis and changes related to the intake of drugs such as non-steroidal anti-inflammatory drugs. Substantial clinical and histological overlap between lymphocytic and collagenous colitis has been described, raising the suspicion that the conditions are two histological manifestations of the same entity, possibly representing different manifestations during the disease course or different stages of disease development. In this review we provide a practical approach for pathologists with focus on diagnostic criteria and differential diagnosis, discuss recent insights into the pathogenesis of disease and the relation to classical chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative colitis.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Objective Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA.
Design Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated.
Results Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61.
Conclusions Although ‘substantial’ to ‘almost perfect’ ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.
Gut 10/2014; DOI:10.1136/gutjnl-2014-307536 · 13.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising readily assessable tool and should therefore routinely be commented on in the pathology report.Modern Pathology advance online publication, 12 September 2014; doi:10.1038/modpathol.2014.104.
Modern Pathology 09/2014; DOI:10.1038/modpathol.2014.104 · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Histologic examination of gastric biopsies is crucial for determining the cause of gastritis. This prospective multicenter study was undertaken to investigate different histologic parameters arguing in favor or against the diagnosis of reactive gastropathy and to correlate findings with patient's symptoms and endoscopic findings. A total of 1,123 individuals aged 15-93 years participated in a prospective multicenter study (histoGERD trial). Diagnosis of Helicobacter gastritis was made following the Updated Sydney System. Diagnosis of reactive gastropathy was based upon Dixon's parameters of foveolar hyperplasia, smooth muscle fibers in the lamina propria and vasodilatation and congestion of mucosal capillaries. Including paucity of acute and chronic inflammatory cells in analysis, a new score with visual analogue scales for the diagnosis of reactive gastropathy was developed. All three histologic parameters in favor of the diagnosis of reactive gastropathy were positively associated with the endoscopic diagnosis of gastritis (p < 0.001), yet negatively with Helicobacter infection (p < 0.001). In contrast, presence of acute and chronic inflammatory cells in lamina propria was positively associated with Helicobacter infection (p < 0.001), yet not with the endoscopic diagnosis of gastritis. Our score demonstrated strong association between histologic and endoscopic diagnoses (p < 0.001), yet not with patient's symptoms. In conclusion, our data prove foveolar hyperplasia, smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy. The proposed score may enhance the diagnostic accuracy. It should be validated in future studies.
Pathology - Research and Practice 08/2014; 210(12). DOI:10.1016/j.prp.2014.08.009 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photodynamic therapy (PDT) by selective photosensitization of cancer cells and subsequent laser application results in local tumor necrosis. However, the effects of PDT on immune function, which may depend on the type of immune response, are controversial. We investigated the immunological changes induced by PDT and the effect of PDT on level and function of regulatory T cells (Treg) in patients with invasive esophageal squamous cell carcinoma (ESCC). We analyzed patient's blood samples before and after PDT. Blood CD4+CD25+CD127-FoxP3+ Treg levels were quantified by FACS, and Treg function was evaluated by coculture proliferation assays with T effector (Teff) cells. We found that PDT abrogated the suppressive capacity of peripheral Treg (Days 7 and 14, p = 0.016) but had no effect on Treg levels. The effect of PDT on Treg function at Day 7 was accompanied by slight but statistically significant increases in peripheral neutrophil granulocytes (p = 0.035) and monocytes (p = 0.013) and a statistically significant increase (approximately 18-fold) in serum IL-6 levels (p = 0.008). In conclusion, PDT abolished Treg function, possibly due to increased IL-6 levels in treated ESCC patients. This may be crucial for an improved therapeutic outcome.
[Show abstract][Hide abstract] ABSTRACT: Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM) system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report.
Cancer Management and Research 07/2014; 6(1):291-300. DOI:10.2147/CMAR.S38827
[Show abstract][Hide abstract] ABSTRACT: Background and aims
Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses.
A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System.
Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals.
Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis.