Prognostic relevance of gastric cancer staging by endoscopic ultrasound.

BACKGROUND: Recent trials and guidelines have established the use of neoadjuvant chemotherapy for resectable UICC stage II to IV gastric cancers. In this setting, preoperative staging is pivotal for correct patient selection. This cohort study was designed to assess the accuracy of endoscopic ultrasound (EUS) and the ability to select correctly patients for neoadjuvant chemotherapy on the basis of survival outcome. METHODS: Eighty-two consecutive Caucasian patients (46 male; median age 72 years) with gastric cancer underwent EUS staging and subsequent surgery without perioperative chemotherapy or radiotherapy. Patients were followed for a median of 800 days postoperatively. Pathology and EUS UICC and T stages were compared and evaluated as predictors of survival using Kaplan-Meier and Cox regression analysis. RESULTS: The overall accuracy of EUS for UICC classification compared with pathology was 62 %, and the accuracy for delineation of UICC I was 89 %. For the therapeutically relevant differentiation of early gastric cancer (UICC stage I), EUS (mean survival, 2,298 days, R2 = 0.23) and pathology (2,461 days, R2 = 0.24) predicted survival equally well. Similar results were obtained for T staging by EUS (mean survival, 2,065 days for uT1/2, R2 = 0.24) or pathology (2,185 days, R2 = 0.22). CONCLUSIONS: EUS identifies the low risk subgroup (uUICC stage I or uT1/2) with similar performance as pUICC stage I or stage pT1/2 in gastric cancer and very similar survival characteristics. EUS thus may be the noninvasive method of choice for preoperative selection of patients for immediate resection versus neoadjuvant chemotherapy.

Staging of rectal cancer by EUS: depth of infiltration in T3 cancers is important.

BACKGROUND: EUS is an established method for staging of rectal cancer. Nevertheless, there are few data about the significance of infiltration depth measured by EUS. OBJECTIVE: Assessment of accuracy of T and N staging by EUS with attention to infiltration depth as provided by EUS. DESIGN: Part retrospective, part prospective study. SETTING: Community and tertiary referral hospital, covering the period before neoadjuvant therapy for advanced rectal cancer was established. PATIENTS: Eighty-three patients (60% men) with untreated rectal cancer. INTERVENTION: EUS examination. MAIN OUTCOME MEASUREMENTS: We examined the correlation between EUS findings and postoperative histology. T3 cancers as diagnosed by EUS were classified into minimally invasive (1-2 mm) or advanced (>2 mm) tumors depending on the depth of infiltration beyond the muscularis propria. RESULTS: Accuracy of T staging and N status was 76% and 63%, respectively. Overstaging by EUS was more common in minimally invasive T3 by EUS (uT3) (8 of 16 [50%]) compared with advanced uT3 tumors (1 of 24 [4%]) (P=.01). Accuracy of EUS discrimination between T1/2 and T3/4 in rectal cancer for all but minimally invasive uT3 rectal tumors was 88%. LIMITATIONS: Partly retrospective analysis. CONCLUSIONS: EUS examination of rectal carcinoma determines T stage with high accuracy. Additionally, it provides information beyond T and N staging. The 50% probability of overstaging patients with minimally invasive uT3N0 by EUS may argue for managing these cancers as stage I disease, ie, to refer the patient for surgery without neoadjuvant therapy.

[A rare cause of severe gastrointestinal bleeding]. / Seltene Ursache einer transfusionspflichtigen gastrointestinalen Blutung.

Upper gastrointestinal hemorrhage represents a common symptom in the internal medical practice. This Case Report depicts a severe gastrointestinal bleeding from an angiosarcoma that required multiple blood transfusion. As shown in this case, the actual cause may initially remain unclear. Repeated tissue sampling is mandatory to confirm a diagnosis and provide adequate treatment. Primary gastrointestinal angiosarcomas are extremely rare and highly aggressive malignant tumors that tend to grow multifocally and metastasise early. The only curative treatment option is radical surgery, thus an early stage diagnosis is crucial. Palliative care for metastatic angiosarkoma is currently a topic for clinical studies.

Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer.

PURPOSE: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting. EXPERIMENTAL DESIGN: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; ≥ 60% TILs), and correlated with pCR rate and DFS. RESULTS: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR. CONCLUSIONS: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747-54. ©2016 AACR.

Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial.

INTRODUCTION: We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT. PATIENTS AND METHODS: The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher. RESULTS: Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were significantly independent predictors for pCR in multivariate analysis (LPBC: OR 2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in multivariate logistic regression analysis (OR 1.2, p = 0.11). CONCLUSION: Confirming previous investigations of our group, we have prospectively validated in an independent cohort that an increased immunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.

[Peer review procedures in pathology - more than ten years of experience in the free state of Saxony]. / Peer Review Verfahren in der Pathologie - mehr als zehn Jahre Erfahrungen im Freistaat Sachsen.

The positive experiences regarding peer review practice go back to the 1990s and can be traced in the position paper of the German Medical Association concerning quality assurance in the field of pathology. This evolved into the initiative of pathologists in Saxony to implement the peer review practice within the remit of their State Medical Association. Since the 14(th) of May 1999 various institutes as well as medical group practices in pathology and cytology have joined forces to undertake voluntary inter-institutional quality control measures. The aim was to improve the process and especially the outcome quality by reviewing each other's quality (analysing samples) on the basis of defined criteria. A positive review outcome report, which will have to be unanimously agreed upon by all participants, will lead to a positive recommendation for a certificate issued by the Medical Association of Saxony. Between 1999 and 2011 a total of 56 peer review proceedings took place. The potentials for improvement concern the problem of "kitchen pathology" still being used in the context of macroscopic description, the quality of microscopic description including the use of correct nomenclature, the quality of tumour classification and immune histological investigations. Statements concerning the advantage of the peer review method in particular refer to the integration of resident pathologists. Due to the long period of implementation of the peer review system und the small number of proceedings, it is not possible to come to a clear conclusion about the improvement or deterioration of quality. During a period of more than 10 years three peer review proceedings were not successful. In this situation, it is appropriate to ask the question of how restrictive peer reviews should be. The three most important aspects for the pathologists in Saxony are: self-determination, learning from each other, and a commitment to quality improvement. So this method set an example of how a quality management method can persist for more than 10 years through voluntary engagement. And the initiative of pathologists in Saxony has given an important impetus to the development of other peer review systems in various health care organisations or disciplines in Germany.