Summary 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.
Background
We recently introduced ex vivo, intra-arterial methylene blue injection as a simple method to improve the lymph node (LN) harvest in gastrointestinal cancer. We now combined it with a ...novel ex vivo sentinel lymph node (evSLN) mapping technique.
Methods
evSLN mapping was performed by subserosal (
n
= 20) or submucosal (
n
= 30) India ink injection. Subsequently, methylene blue was injected intra-arterially to enhance visibility of all LNs to improve the overall LN harvest. Manual LN dissection was carried out after fixing overnight. evSLNs nodes were identified by detecting carbon particles during histological examination. In primary node-negative cases, all detected LNs were step sectioned and immunohistochemically stained for pan-cytokeratin.
Results
India ink injection was easy to perform. Methylene blue injection failed in 1 case. The mean lymph node harvest was 42 ± 18 LNs, and the SLN detection rate was 78%. The sensitivity for detecting metastases was 75%. The mean SLN number was 3 ± 1. LN metastases were found in 20 of 47 malignant cases (43%). Skip metastases occurred in 4 cases. Of these cases, 3 showed involvement of at least 1 entire LN. True upstaging (N0 → N1mi) was found in 1 of 23 cases (4%) within a SLN after advanced evaluation.
Conclusions
Combination of methylene blue technique and ex vivo sentinel mapping is feasible, easy to perform, and cost effective. It guarantees an optimal LN harvest and has the potential to heighten the sensitivity of metastasis detection.
Background
Correct tumor localization is crucial for proper surgical therapy in colorectal cancer. Intraoperative visualization of the lesion is facilitated by preoperative colonoscopic tattooing, ...regardless of whether an open or laparoscopic approach is employed.
Objective
This pilot study tests the hypothesis that colonoscopic tattooing can serve the additional role of sentinel lymph node (SLN) mapping.
Methods
We collected 5 prospective and 16 retrospective cases, in which colonoscopic tattooing was applied and surgery was performed. Nineteen of these cases showed colorectal cancer. High-grade intraepithelial neoplasia was found in two cases. All lymph nodes (LNs) were histologically assessed for metastasis and carbon particles, and those that tested positive were registered as carbon-containing lymph nodes (CcLNs). Subsequently, additional step sections were cut and immunohistochemistry was performed on all lymph nodes of the malignant cases.
Results
A total number of 311 lymph nodes were investigated. CcLNs could be identified in 17 of 21 cases (detection rate: 81%). The histomorphology of CcLNs was identical to that known from carbon as a sentinel marker dye. The mean CcLN number was 2 ± 2 (range 1–6). After primary evaluation, one metastasis was detected in a case where a CcLN was not observed. All other cases showed no positive LNs. After step sectioning and immunohistochemical staining, one additional micrometastasis was found in a CcLN, resulting in upstaging from N0 to N1 (mi).
Conclusion
Our findings support the thesis that colonoscopic tattooing holds the potential for SLN mapping. Therefore, a prospective study with an appropriate case number should follow this pilot study to clarify the clinical value of this finding.
Recently, we introduced ex vivo intra-arterial methylene blue injection into the inferior mesenteric artery as a novel method to improve lymph node (LN) harvest in rectal cancer. We have now adapted ...this method to the other segments of the colon. A total of 60 cases were enrolled. Primary LN dissection was followed by fat clearance and a secondary dissection. The mean +/- SD primary LN harvest differed highly significantly with 35 +/- 18 and 17 +/- 10 LNs in the methylene blue-stained and unstained groups, respectively. Primary insufficient LN harvest occurred in 8 cases of the unstained group and in only 1 case of the methylene blue-stained group (P = .0226). After secondary dissection, upstaging was seen exclusively in the unstained group. The time/LN ratio differed significantly with 0.9 and 0.6 min/LN in the unstained and methylene blue-stained groups, respectively. Intraarterial methylene blue injection is recommended as a routine technique in the histopathologic study of colon cancer.
Background
Exact lymph node (LN) staging is crucial for prognosis estimation and treatment stratification in gastric cancer. Recently, a new concept for improving LN harvest and the accuracy of LN ...staging was introduced. It combines methylene blue-assisted lymph node dissection (MBLND) with a new ex vivo sentinel lymph node (evSLN) mapping technique. The purpose of this study was to investigate these techniques in a prospective and randomized manner.
Methods
A total of 50 patients with proven or suspicious gastric cancer were enrolled. Twenty-five patients each were randomized to the conventional technique (Unstained) or MBLND (Methylene). In 46 cases, additional evSLN mapping with black ink as a marker dye was performed.
Results
Methylene blue-assisted lymph node dissection was associated with a highly significantly improved LN harvest (36 ± 10 vs. 21 ± 10;
P
< 0.001). The biggest differences were seen in LNs ≤ 6 mm. In contrast to the conventional technique, neither partial gastrectomy nor preoperative chemotherapy influenced LN harvest in the methylene group. The evSLN detection rate, sensitivity, and accuracy were 87, 81, and 93%, respectively. Isolated tumor cells were detected after immunohistochemical staining in 3 of 17 cases (18%). The probability of carrying a metastasis was two times higher in evSLNs compared to non-evSLNs (44 vs. 23%;
P
< 0.001).
Conclusions
Methylene blue-assisted lymph node dissection is a highly effective method of improving the LN harvest in gastric cancer. Further application of evSLN mapping is feasible and has the potential to heighten the sensitivity of metastasis detection.
Background & Aims Endoscopic submucosal dissection (ESD) is a promising technique in the treatment of large premalignant and early malignant gastrointestinal lesions. In contrast to Japan and Asian ...countries, few data are available from Western countries. The objective of this study was to assess the feasibility of ESD in a European center, with special regard for the success rate and learning curve. Methods Over a 4-year-period, 82 epithelial or submucosal lesions were referred for ESD. Seventy-one ESDs were performed (51 gastric, 17 rectal, 2 esophageal, and 1 duodenal). Resection rates, procedure times, specimen sizes, complications, and recurrences were noted. The mean follow-up period was 15 months. Results Specimen size increased significantly ( P < .05) and procedural duration decreased significantly ( P < .005) over time. En bloc resection rates and R0 en bloc resection rates were 77.1% and 65.7%, respectively, in the first half of the study and increased to 86.1% and 72.2%, respectively, in the second half ( P = NS). No recurrence was observed after R0 en bloc resection whereas the recurrence rate was 38.5% after piecemeal resections ( P < .001). Two perforations in the first series were treated by surgery; 2 other perforations, 8 minor bleedings, and 2 pyloric stenoses were treated endoscopically. Conclusions ESD is technically feasible and shows promising results in this German single-center-study. ESD is time consuming and difficult but shows a learning curve resulting in a decrease of the procedural duration over time. R0 en bloc resection is mostly possible and can avoid the risk of local recurrence.
Benign lesions in the gastrointestinal tract characterized by an increase of elastic fibers in the submucosal and mucosal layer are termed elastoma, elastosis, elastofibroma or elastofibromatous ...change, and present mostly as polyps. Twenty-seven such cases are published in the English and French literature. Some lesions are similar to alterations which are well-known from elastofibroma dorsi of the scapular region. The morphology is highly suggestive of amyloid, but the results of Congo red staining are consistently negative. The etiology of these alterations remains unclear. Some authors consider elastoma a reactive process due to an injury, others speculate about a link to a systemic disease. We present six cases including a right and a left hemicolectomy specimen that presented as polypoid alterations of the ileum and the colon, respectively. Histologically, we found an impressive increase in fine fibrillar elastic fibers that showed a clear association to submucosal vessels. We did not observe elastofibroma-like alterations. After comparing literature cases, we conclude that elastofibromatous change consists either of two different stages, or even more likely, of two different entities. We propose the term angioelastosis for cases we describe in our study to emphasize the involvement of submucosal vessels.
The epidermal growth factor (EGF) receptor and its various ligands (EGF, TGF-alpha, amphiregulin, heparin-binding (HB)-EGF, heregulin, betacellulin) seem to be involved in the growth regulation of ...intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. However, few quantitative data investigating the impact of tumor-EGF receptor levels in gastrointestinal carcinomas on tumor stage and prognosis are available. Therefore, EGF receptors were quantitatively determined in colorectal carcinomas in comparison to adjacent normal mucosa by 125IEGF-binding studies. EGFR capacity was increased in advanced invasive colorectal carcinomas (T1/2 vs. T3/4 tumors, p<0.001) and advanced UICC stages (UICC I vs. UICC II/III, p<0.001). These findings were confirmed with quantitative 125IEGF autoradiography performed on frozen tissue slides and analyzed by laser densitometry (p=0.020). EGF receptor analysis with immunohistochemistry with EGFR antibodies directed against the extracellular domain of the receptor was not correlated with tumor invasion or prognosis. mRNA-expression of EGFR ligands was investigated using semiquantitative RT-PCR amplification using specific primers. RT-PCR transcripts of EGFR ligands (EGF, TGF-alpha, HB-EGF, and amphiregulin) were detected in both carcinomas and normal mucosa, indicating that autocrine growth stimulation of colorectal carcinomas is mediated by coexpression of EGF receptor ligands and upregulation of EGF receptors. Survival of colorectal cancer patients with increased tumor EGF receptor levels was significantly reduced in comparison to patients with low/unchanged tumor EGF receptor levels (mean survival+/-SD, 36.2+/-4.0 vs. 46.8+/-4.3 months; p=0.017). Further studies investigating EGF receptor levels in gastric cancer patients have shown that increased tumor EGF receptor levels were associated with poor prognosis in gastric cancer patients with tumors localized distal from the cardia. Several specific EGF receptor tyrosine kinase inhibitors have recently entered clinical phase I-III studies, with promising antitumor effects in several tumors, including gastrointestinal cancer. Therefore, patients with invasive gastric or colorectal carcinomas might benefit from therapies specifically blocking EGFR-mediated signal transduction.
Background/Aims: Preconditioning of livers with the atrial natriuretic peptide (ANP) markedly reduces hepatic ischemia-reperfusion injury. Aim of this study was to characterize the influence of ANP ...preconditioning on necrotic and apoptotic cell death and on proliferation.
Methods: Rat livers were perfused with Krebs-Henseleit buffer with or without ANP or its second messenger analogue 8-Bromo cyclic guanosine monophosphate (8-Br cGMP) for 20 min, stored in cold University of Wisconsin solution (24 h), and reperfused for up to 120 min. Apoptosis and necrosis were determined using biochemical and morphological criteria, proliferation was assessed by Ki67 histochemistry.
Results: Apoptosis peaked after 24 h of cold ischemia. Preconditioning with both ANP and 8-Br-cGMP significantly reduced caspase-3-like activity and the number of triphosphate nick-end labelling-positive cells. Reduction of apoptosis was significant for hepatocytes, but not for endothelial cells. After ischemia, degenerative cell changes were clearly reduced in ANP pretreated livers. After reperfusion, ANP preconditioning led to a significant reduction of necrotic hepatocytes and endothelial cells in periportal zones. Cell proliferation was not affected by preconditioning.
Conclusions: ANP reduces necrotic and apoptotic cell death without affecting the proliferation status. The protection takes place mainly in the periportal area and seems to be most prominent against necrosis of hepatocytes and endothelial cells during reperfusion.
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