Search

The tumor stroma ratio (TSR) is a promising prognostic biomarker in colon cancer, which could provide additional risk stratification for therapy adaption. The objective of our study was the investigation of the prognostic significance of TSR at different tumor sites in a simple semiautomatic approach with the open-source program ImageJ. We investigated 206 pT3 and pT4 adenocarcinomas of no special type. According to our established thresholds, 31 tumors (15%) were classified as low tumor proportion (TP) (≤ 15% TP), 42 tumors (20%) were classified as high TP (≥ 54% TP), and 133 tumors (65%) were classified as medium TP. High and low TP were associated with an adverse overall survival in comparison to medium TP (p = 0.001 and p = 0.03). Furthermore, the TP was an independent risk factor of occurrence of distant metastasis next to T status, microsatellite status, and tumor budding. The 5-year survival rate was 49% in patients with high TP, 48% in patients with low TP, and 68% in patients with medium TP (p = 0.042, n = 160). Patients with a high TP had less often tumor budding (p = 0.012), lymphovascular invasion (p = 0.049), and less harvested lymph nodes (p = 0.042) in comparison to low TP tumors. The results provide first evidence that a high tumor proportion/low stroma proportion is also associated with an adverse prognosis and that this subgroup might be difficult to identify with other classical histopathologic characteristics that are linked to an adverse prognosis.

Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002-2011) colon carcinoma (pT3/4, N+/-, M0). High-grade tumor budding/budding grade 3 (defined as majority assessment among the investigators) was significantly associated with an adverse outcome (overall survival p = 0.03, cancer-specific survival p = 0.08) and the occurrence of distant metastasis (p = 0.009). However, a detailed analysis of the rating results of the individual investigators revealed that only ratings of one investigator (advanced resident) were associated with an adverse outcome (p = 0.01 cancer-specific survival, overall survival p = 0.09, distant metastasis p = 0.002). The results of another investigator (consultant) were significantly associated with distant metastasis (p = 0.007). The kappa values among the investigators have a range between 0.077 and 0.357 (median 0.166). Total agreement of all investigators existed in 109 cases (44.7%). Our results demonstrate that the evaluation of tumor budding on H&E slides in pT3/4 colon cancer goes along with a considerable interobserver variability among investigators of different levels of experience. Furthermore, our results reveal that these findings directly influence the prognostic value.

Background: Evidence-based medicine (EbM) is a vital part of reasonable and conclusive decision making for clinicians in daily clinical work. To analyze the knowledge and the attitude of surgeons towards EbM, a survey was performed in the UK and Germany., Methods: A web-based questionnaire was distributed via mailing lists from the Royal College of Surgeons of England (RCSE) and the Berufsverband Deutscher Chirurgen (BDC). Our primary aim was to get information about knowledge of EbM amongst German and British surgeons., Results: A total of 549 individuals opened the questionnaire, but only 198 questionnaires were complete and valid for analysis. In total, 40,000 recipients were approached via the mailing lists of the BDC and RCSE. The response rate was equally low in both countries. On a scale from 1 (unimportant) to 10 (very important), all participants rated EbM as very important for daily clinical decision making (7.3 ± 1.9) as well as for patients (7.8 ± 1.9) and the national health system (7.8 ± 1.9). On a scale from 1 (unimportant) to 5 (very important), systematic reviews (4.6 ± 0.6) and randomized controlled trials (4.6 ± 0.6) were identified as the highest levels of study designs to enhance evidence in medicine. British surgeons considered EbM to be more important in daily clinical work when compared to data from German surgeons (7.9 ± 1.6 vs. 6.7 ± 2.1, p < 0.001). Subgroup analysis showed different results in some categories; however, a pattern to explain the differences was not evident. Personal requirements expressed in a free text field emphasized the results and reflected concerns such as broad unwillingness and lack of interdisciplinary approaches for patients (n = 59: 25 in the UK and 34 in Germany)., Conclusion: The overall results show that EbM is believed to be important by surgeons in the UK and Germany. However, perception of EbM in the respective health system (UK vs. Germany) may be different. Nonetheless, EbM is an important tool to navigate through daily clinical problems although a discrepancy between the knowledge of theoretical abstract terms and difficulties in implementing EbM in daily clinical work has been detected. The provision of infrastructure, courses and structured education as a permanent instrument will advance the knowledge, application and improvement of EbM in the future., (© 2014 S. Karger AG, Basel.)

Background: Most investigations of thyroidectomy for metastatic renal cell carcinoma (RCC) are case studies or small series. This study was conducted to determine the contribution of clinical and histopathologic variables to local recurrence in the neck and overall survival after thyroidectomy for RCC metastases., Methods: The medical records of 140 patients with thyroidectomy for metastatic RCC performed between 1979 and 2012 at 25 institutions in Germany and Austria were analyzed., Results: The median interval between nephrectomy and thyroidectomy was 120 months. Concurrence of thyroid and pancreatic metastases was present in 23 % of the patients and concurrence of thyroid and adrenal metastases in 13 % of the patients. Clinical outcome data were available for 130 patients with a median follow-up period of 34 months. The 5-year overall survival rate was 46 %, and 28 % of patients developed a local neck recurrence at a median of 12 months after thyroidectomy. Multivariate analysis showed that invasion of adjacent cervical structures (hazard ratio [HR] 3.2; p = 0.001), patient age exceeding 70 years (HR 2.5; p = 0.004), and current or past evidence of metastases to nonendocrine organs (HR 2.4; p = 0.003) were independent determinants of inferior overall survival. Conversely, invasion of adjacent cervical structures (HR 12.1; p < 0.0001) and year of thyroidectomy (HR 5.7 before 2000; p < 0.0001) were shown to be independently associated with local recurrence in the neck by multivariate analysis., Conclusions: Although significant improvement of local disease control in patients with thyroid metastases of RCC has been achieved during the last decade, overall outcome continues to be poor for patients with locally invasive thyroid metastases.

Lymph node staging is of paramount importance for prognosis estimation and therapy stratification in colorectal cancer. A high number of harvested lymph nodes is associated with an improved outcome. Methylene blue-assisted lymph node dissection effectively improves the lymph node harvest and ensures sufficient staging. Now, the effect on node positivity rate and stage-related outcome was investigated. The study cohort with advanced lymph node dissection consisted of 669 colorectal cancer cases of all stages, which were collected between 2007 and 2012. A historical collection of 663 cases investigated with conventional techniques between 2002 and 2004 served as control. Lymph node harvest was dramatically improved in the study group with mean lymph node numbers of 34 ± 17 vs 13 ± 5 (P<0.001) and sufficient staging rates of 98% vs 62% (P<0.001). However, neither the rate of nodal positive cases (37% vs 37%; P = 0.98) nor the rate of N2 cases differed between the two groups (14% vs 13%; P = 0.80). Furthermore, no differences were found concerning the outcome in both groups. The advanced lymph node dissection technique guarantees adequate histopathological lymph node staging in virtually all cases of colorectal cancer and is therefore extremely helpful. The hypothesis that it also provides a higher sensitivity in detecting metastases, however, could be not proved.

To date, the clinical value of lymph node size in colon cancer has been investigated only in a few studies. Only in radiological diagnosis is lymph node size routinely recognized, and nodes ≥10 mm in diameter are considered pathologic. However, the few studies regarding this topic suggest that lymph node size is not a reliable indicator of metastatic disease. Moreover, we hypothesized that increasing lymph node size is associated with favorable outcome. By performing a morphometric study, we investigated the clinical significance of lymph node size in colon cancer in terms of metastatic disease and prognosis. A cohort of 237 cases with excellent lymph node harvest (mean lymph node count: 33±17) was used. The size distribution in node-positive and -negative cases was almost identical. In all, 151 out of the 305 metastases detected (49.5%) were found in lymph nodes with diameters ≤5 mm. Only 25% of lymph nodes >10 mm showed metastases. Minute lymph nodes ≤1 mm were involved only very rarely (2 of 81 cases). In 67% of the cases, the largest positive lymph node was <10 mm. The prognostic relevance of lymph node size was investigated in a subset of 115 stage I/II cases. The occurrence of ≥7 lymph nodes that were >5 mm in diameter was significantly associated with better overall survival. Our data show that lymph node size is not a suitable factor for preoperative lymph node staging. Minute lymph nodes have virtually no role in correct histopathological lymph node staging. Finally, large lymph nodes in stage I/II disease might indicate a favorable outcome.

Maspin has been characterized as a potent tumor suppressor in many in vitro and in vivo studies. In contrast, in stage III colon cancer, an association with shorter overall survival as well as sensitivity to chemotherapy was found for cases with nuclear maspin expression. Because 20% of node-negative colorectal cancer cases show a fatal clinical course, we hypothesized that immunohistochemical maspin expression could be of help to identify higher-risk cases. Therefore, we analyzed survival in a study employing 156 cases of stage I/II colorectal cases. Immunohistochemical cytoplasmic and/or nuclear maspin expression was found in 72% and 48% of the cases, respectively. Significant correlations between cytoplasmic expression and high tumor grade (P < .01) and between nuclear expression and tumor budding (P < .001) were shown. No differences concerning overall survival and immunohistochemical maspin expression were found when the complete collective was analyzed. However, evaluation of the pT3 cases revealed a highly significant worse mean overall survival of cases with a combination of nuclear expression and cytoplasmic loss of maspin compared to cases with the opposite expression pattern nuclear loss and cytoplasmic expression (mean overall survival 40 versus 63 months, respectively; P < .001). The other possible combinations (complete positive and complete negative) showed intermediate mean overall survival times with 54 and 49 months, respectively. Our findings suggest a compartment-dependent function of maspin in colorectal cancer, which can be useful in identifying stage II cases with a higher risk for fatal outcome with a possible benefit from adjuvant chemotherapy., (Copyright 2010 Elsevier Inc. All rights reserved.)