Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

BACKGROUND: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. METHODS: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. RESULTS: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). CONCLUSION: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance

Diagnostic Confidence of Run-Off CT-Angiography as the Primary Diagnostic Imaging Modality in Patients Presenting with Acute or Chronic Peripheral Arterial Disease

Objectives To investigate the reliability of CT-angiography of the lower extremities (run-off CTA) to derive a treatment decision in patients with acute and chronic peripheral artery disease (PAD). Materials and Methods 314 patients referred for run-off CTA were includ-ed in this retrospective study. First, diagnostic confidence of run-off CTA to derive a treat-ment decision was assessed in an interdisciplinary vascular conference using a 2 point scale (sufficient or not sufficient diagnostic confidence) and compared with the image quality eval-uated by two readers in consensus in four different levels (abdominopelvic, thigh, calf, foot arteries). Second, reliability of treatment decision was verified in all patients undergoing re-vascularization therapy. Results Diagnostic confidence of run-off CTA to derive a treatment deci-sion was sufficient in all patients with acute and in 97% of patients (215/221) with chronic PAD, whereas the rate of run-off CTA with non-diagnostic image quality was considerably higher in the calf and foot level (acute vs. chronic; calf: 28% vs.17%; foot: 52% vs. 20%). Reliability of treatment decision was superior for patients with chronic (123/133 = 92%) than for patients with acute PAD (64/78 = 82%, P = 0.02). Conclusion Run-off CTA is a reliable imaging modality for primary diag-nostic work-up of patients with acute and chronic PAD

Animal experimental trials using rat colitis models

Ätiologie und Pathogenese der chronisch entzündlichen Darmerkrankungen, Morbus Crohn und Colitis ulcerosa, sind trotz zahlreicher neuer wissenschaftlicher Erkenntnisse ungeklärt. Das Ziel dieser Arbeit war es, den Stellenwert der Mikrozirkulation in diesem Zusammenhang zu evaluieren. Dazu erfolgten intravitalmikroskopische Untersuchungen am gesunden Darm sowie bei zwei verschiedenen Colitis-Modellen der Ratte. Bei der TNBS-Colitis kommt es im akuten, bei der Mitomycin C-Colitis im chronischen Stadium der Entzündung zu signifikanten Störungen der mukosalen Mikrozirkulation. Schließlich wurden im Rahmen einer Interventionsstudie verschiedene Substanzen appliziert. Es zeigt sich, dass die Gabe des selektiven Endothelin-A-Rezeptor-Antagonisten LU-135252 zu einer signifikanten Besserung sämtlicher Mirkozirkulationsparameter sowie auch der klinischen Befunde gegenüber der Kontroll-TNBS-Colitisgruppe führt. Die Zufuhr des selektiven COX-2-Inhibitors NS-398 hat denselben Effekt, wenn auch nicht so ausgeprägt. Der hemmende Einfluss beider Substanzen auf die Leukozyten–Endothel–Interaktion scheint hierbei eine Rolle zu spielen. Da die Endothelin-A-Rezeptor-Blockade allerdings hinsichtlich der Colitis-Aktivtät signifikant effektiver ist, muss ein weiterer Mechanismus im Sinne einer direkten Wirkung auf den kapillären Blutfluss vorliegen, was die pathogenetische Bedeutung der Mikrozirkulation für die Progression der Colitis unterstreicht.The etiology and pathogenesis of chronic inflammatory bowel disease, Crohn’s disease and ulcerative colitis, remains unclear despite numerous new scientific findings. The aim of this study was to evaluate the role of the microcirculation in this context. For this purpose, intravital microscopic examination of the healthy bowel and in two different rat colitis models was performed. Significant disturbances of the mucosal microcirculation were observed at the acute inflammatory stage of TNBS colitis and at the chronic stage of mitomycin C colitis. Finally, different substances were applied in an intervention study. Application of the selective endothelin-A receptor antagonist LU-135252 resulted in a significant improvement of all microcirculatory parameters and clinical findings compared to the control TNBS colitis group. The same effect, though not as pronounced, was seen with the selective COX-2 inhibitor NS-398. The inhibitory influence of the two substances on leukocyte-endothelium interaction seems to play a role. However, there may be another mechanism like a direct effect on capillary blood flow, since endothelin A receptor blockade is significantly more effective with regard to colitis activity, underscoring the pathogenetic role of the microcirculation on the progression of colitis

The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status

The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status

Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas.

5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0).Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival.129 patients (48 female) with a mean follow-up of 129.1 months were identified. 5-year overall survival was 83.9%, 5-year tumor related survival was 95.1%. Poorly differentiated medullary cancer subtypes (p<0.001) and positive vein invasion (p<0.001) were identified as risk factors for decreased overall-and tumor related survival. Ki-67 (p = 0.012) and TP53 mutation (p = 0.044) were the only immunohistochemical markers associated with worse overall survival but did not reach significance for decreased tumor related survival.In the presented study patients with AGE/S in stage UICC-I-N0 had a better prognosis as previously reported for Caucasian patients. Poorly differentiated medullary subtype was associated with reduced survival and should be considered when studying prognosis in these patients

Example of a run-off CTA with sufficient diagnostic confidence despite non-diagnostic image quality.

<p>84 y old female with acute onset of severe right leg pain. MIP (a,b) and volume rendering technique image (c) of run-off CTA revealed a thromboembolic occlusion with lack of arterial enhancement of the large arteries of the right leg from the external iliac artery (white arrow) down to the foot. Immediate surgical thrombectomy confirmed the finding of run-off CTA.</p

Fontaine Stage of patients with acute or chronic PAD depending on run-off CTA with sufficient (DC+) and insufficient diagnostic confidence (DC−).

<p>P-Value of χ²-test.</p><p>Fontaine Stage of patients with acute or chronic PAD depending on run-off CTA with sufficient (DC+) and insufficient diagnostic confidence (DC−).</p

Proportion of patients with non-diagnostic image quality (IQ-) due to severe vessel calcifications (A) or insufficient vessel contrast (B) dependent on peripheral arterial disease (PAD) manifestation and arterial level.

<p>The total number of patients (black numbers) as well as the subset of patients with insufficient diagnostic confidence of run-off CTA (DC−, white numbers) is given for each subgroup. DC− = insufficient, DC+ = sufficient diagnostic confidence. * = P <0.05, *** = P<0.001, n.s. = no significance, P-Value of χ²-test.</p