Data from Progression and Tumor Heterogeneity Analysis in Early Rectal Cancer
Esther H. LipsRonald van EijkEelco J. R. de GraafPascal G. DoorneboschNoel F.C.C. de MirandaJan OostingTom M. KarstenPaul H.C. EilersRob A.�E.�M. TollenaarTom van WezelHans Morreau
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<div>Abstract<p><b>Purpose:</b> Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression.</p><p><b>Experimental Design:</b> We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis.</p><p><b>Results:</b> Five specific “malignant” events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (<i>r</i> = 0.807; <i>P</i> < 0.001).</p><p><b>Conclusion:</b> Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity.</p></div>Keywords:
Submucosa
Tumor progression
Delayed postpolypectomy bleeding occurs more frequently after hot resection than after cold resection.To elucidate the underlying mechanism, we performed a histological comparison of tissue after cold and hot snare resections.This is a prospective study, registered in the University Hospital Medical Information Network (UMIN000020104).This study was conducted at Aizu Medical Center, Fukushima Medical University, Japan.Fifteen patients scheduled to undergo resection of colorectal cancer were enrolled.On the day before surgery, 2 mucosal resections (hot and cold) of normal mucosa were performed on each patient using the same snare without saline injection. The difference was only the application of electrocautery or not. Resection sites were placed close to the cancer to be included in the surgical specimen.The primary outcome measure was the depth of destruction. Secondary outcome measures included the width of destruction, depth of the remaining submucosa, and number of vessels remaining at the resection sites. The number and diameter of vessels in undamaged submucosa were also evaluated.All cold resections were limited to the shallow submucosa, whereas 60% of hot resections advanced to the deep submucosa and 20% to the muscularis propria (p < 0.001). There was no significant difference in the width of destruction. The number of remaining large vessels after hot resections trended toward fewer (p = 0.15) with a decreased depth of remaining submucosa (p = 0.007). In the deep submucosa, the vessel diameter was larger (p < 0.001) and the number of large vessels was greater (p = 0.018).Histological assessment was not blinded to the 2 reviewers. Normal mucosa was used instead of adenomatous tissue.Hot resection caused damage to deeper layers involving more large vessels. This may explain the mechanism for the reduced incidence of hemorrhage after cold snare polypectomy. See Video Abstract at http://links.lww.com/DCR/A631.
Submucosa
Muscularis mucosae
Colorectal Surgery
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The authors report a case of an oesophageal cancer limited to the mucosa and the submucosa. This case is interesting because of its long history for more than 18 months, the difficulty of fiberoptic diagnosis and the diagnostic value of rigid instruments completed via vital staining by o-toluidine.
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Human stomach
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Objective To assess the clinical efficacy and safety of endoscopic submucosal dissection(ESD) for flat polyp and submucosal tumor(SMT) of the gastrointestinal tract. Methods Total 58 patients with mucosal tumor of the gastrointestinal tract diagnosed by endoscopy were examined using endoscopic ultrasonography(EUS). Among the cases, 25 lesions were within the submucosa, 16 lesions were within the submucosa muscularis and 17 in the submucosa propria. The cases were managed by ESD with a HOOK and IT knife. After injection of physiological saline solution into the submucosal layer to separate the lesion from the muscle layer, the mucosa surrounding the lesion was pre-cut, and the connective tissue of the submucosa beneath the lesion was dissected. Then, the lesion was resected completely. Results All lesions were successfully resected with ESD. The resected lesions sized 0.4~3.4 cm in diameter(mean,1.5 cm). The mean ESD procedure time was 40 min(ranged from 15 to 95 min). None of the patients showed delayed bleeding after ESD. Histological evaluation showed that the tunica of the tumors was intact, and both the lateral and basal margins of the specimens were free of tumor cells. Conclusion ESD is an efficacious and safe procedure for the treatment of SMT of the gastrointestinal tract. It is possible to completely resect submucosal lesions and provide sufficient pathological information.
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Endoscopic submucosal dissection
Muscularis mucosae
Endoscopic mucosal resection
Muscular layer
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One of the malignant forms of pleomorphic adenomas (PA) is carcinoma ex pleomorphic adenoma (CA-ex-PA). Carcinoma ex pleomorphic adenoma is an uncommon malignant tumor with high aggressive behavior and poor prognosis. However, there are a few studies in this topic in the recent literature. Furthermore, the lesions are uncommon and often have a difficult diagnosis by clinicians and pathologists, because the residual small PA component and various malignancy subtypes may be present. In this study, we reviewed the recent studies in about clinical, radiographical, histopathological and molecular features of CA-ex-PA.
Ex vivo
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Submucosa
Endoscopic submucosal dissection
Endoscopic mucosal resection
Muscular layer
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Endoscopic mucosal resection
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To accurately document the incidence of lymph node metastases (LNM) in early esophageal adenocarcinoma with regard to the depth of invasion of the mucosa or submucosa.Endoscopic therapy is now being proposed as a viable treatment for submucosal esophageal adenocarcinoma. If such treatments are appropriate, then the risk of LNM must be shown to be low in these tumors.One hundred nineteen consecutive patients underwent radical esophagectomy alone for treatment of superficial esophageal adenocarcinoma or high-grade dysplasia. The resection specimens were analyzed by an expert gastrointestinal pathologist and the presence of LNM and the depth of tumor invasion were recorded. Depth of invasion was classified as either confined to the mucosa, the first third of the submucosa, the middle third of the submucosa, or the final third of the submucosa.Fifty-four patients had high-grade dysplasia or tumors confined to the mucosa with no evidence of LNM (0/54, 0%), 65 patients had tumor invading the submucosa with 8 patients having LNM (8/65, 12%). Subclassification of submucosal invasion showed that 5 of 22 "first third of the submucosa" tumors had LNM (23%), 1 of 24 "middle third of the submucosa" tumors had LNM (4%), and 2 of 19 "final third of the submucosa" tumors had LNM (11%).Invasion of the submucosa is associated with significant risk of LNM. Patients with submucosal invasion are not suitable for endoscopic treatment and surgical resection remains the gold standard treatment for patients with submucosal adenocarcinoma who are fit to undergo the procedure.
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Pleomorphic adenoma, the most common type of tumor of the parotid gland, may transform into a malignant tumor. In the current study, we investigated whether the expression of cyclooxygenase-2 (COX-2) is elevated in adenocarcinoma as compared to pleomorphic adenoma. Ten pleomorphic adenomas and 10 adenocarcinomas were examined. The tumor specimens were immunohistochemically stained with antibodies against COX-2 and Ki-67. The labeling indices of COX-2 in pleomorphic adenoma and adenocarcinoma were 6.0% +/- 4.1% and 16.1% +/- 4.6%, respectively, and those of Ki-67 in pleomorphic adenoma and adenocarcinoma were 0.77% +/- 0.62% and 6.9% +/- 6.6%, respectively. The labeling indices of both COX-2 and Ki-67 were significantly greater (p < .001) in adenocarcinoma than in pleomorphic adenoma. Together with the biological effects of COX-2, these results suggest that overexpression of COX-2 plays a crucial role in the pathogenesis of malignant transformation of pleomorphic adenoma in the parotid gland.
Malignant Transformation
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A 41-year-old male was referred for a gastric sub-epithelial lesion. EGD/EUS showed a sub-epithelial lesion in the gastric body extending to the submucosa measuring 17 mm. He opted for Endoscopic full-thickness resection.
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Endoscopic mucosal resection
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