Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer.

The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors.

Cytokeratins 7 and 20 and mucin core protein expression in esophageal cervical inlet patch.

Cervical inlet patch (CIP) is defined by the presence of gastric mucosa within the first few centimeters of the esophagus. Several endoscopic series have demonstrated a frequent association of CIP with Barrett's esophagus (BE) suggesting a pathogenetic link. A histochemical study reporting the presence of acid mucin in CIP, including sulfomucin, supports this hypothesis. We evaluated mucin core protein expression and cytokeratins 7 and 20 (CK7/CK20) pattern in biopsies of CIP, normal antrum, and BE to comment on a possible relationship of CIP with BE. We observed that both lesions have similar cytokeratin patterns with mixed CK7/CK20 reactivity on the surface and pits and lone CK7 positivity in the glands. MUC5AC was strongly expressed on the surface and pits but not in the glands of CIP and antral mucosa. Within BE, MUC5AC positivity was noted not only on the surface and pits but also in the glands. MUC6 similarly decorated the glands of CIP and BE. MUC2 was expressed rarely in CIP with goblet cells but conspicuously on the surface and pits of BE. MUC5B was seen in both CIP and BE and rarely in the antral mucosa. The similarities between CIP and BE but not with normal antral mucosa fits with the hypothesis that both lesions may originate from submucosal esophageal mucous glands. Two pathogenetic pathways can be entertained: focal upper esophageal mucosal misdevelopment in pediatric population and patchy metaplastic replacement of squamous mucosa in adults with gastroesophageal reflux disease.

Role of lymphocytic immunophenotyping in the diagnosis of gluten-sensitive enteropathy with preserved villous architecture.

Clinically significant gluten-sensitive enteropathy (GSE) can be associated with architecturally normal small bowel villi and evenly distributed increased intraepithelial T lymphocytes (IELs). This distribution pattern of IELs has been shown to be a sensitive feature of GSE but to be of relatively low specificity, thus limiting its usage as a diagnostic marker. We demonstrate herein the potential diagnostic role of IEL immunophenotyping. We show that a top-heavy distribution pattern of CD3+ IELs is a sensitive diagnostic feature of GSE. Despite overlap between GSE and non-GSE patients, the difference is underscored when using a tip-to-base ratio. Of the GSE patients, 87.5% showed a tip-to-base ratio >1.7 compared with only 12.5% of non-GSE patients and none in controls. This pattern was retained in 50% of treated GSE patients, although the CD3+ tip-IEL scores were significantly smaller. Conversely, CD8 immunostaining appears of limited diagnostic value. The discrepancy in distribution of CD3+ and CD8+ IELs between GSE and non-GSE patients can be explained by the presence of CD4- CD8- TCR-gamma delta+ IELs which, have been reported in GSE. Since the immunophenotyping of T- IELs is feasible with readily available antibodies, and given the clinical benefits for patients with 'latent' GSE, we advocate using CD3 immunostaining to triage patients with normal villi and increased IELs.

Histopathologic aspects of photodynamic therapy for dysplasia and early adenocarcinoma arising in Barrett's esophagus.

The efficacy of photodynamic therapy (PDT) is currently evaluated for the treatment of superficial neoplasms arising in Barrett's esophagus (BE). An accurate assessment of this technique requires the evaluation of biopsies before and after treatment. However, despite the importance of pathology, only a limited number of studies have systematically assessed the mucosal changes after PDT. To evaluate mucosal changes after PDT, and pathologic variables that may impact on the success of this therapy, we analyzed the pre- and post-PDT biopsies of a cohort of patients treated by this modality. Thirty-three patients (mean age, 71 years) with high-grade dysplasia (HGD) and/or intramucosal carcinoma (IMC) arising in BE and followed up after PDT using Porfimer sodium form the basis of this study. In all patients, a review of all pre- and post-PDT biopsies was performed. The variables recorded included the histologic grade and architecture of neoplasms, the distribution of neoplasms, and squamous re-epithelialization. IMC and HGD coexisted in the pre-PDT biopsies of 18 patients (54.5%). IMC and HGD showed a prominent tubular proliferation in 14 patients and displayed a papillary pattern (at least partially) in 19 patients. In post-PDT, patches of specialized columnar epithelium were buried under squamous epithelium in 17 patients (51.5%), and foci of dysplasia/carcinoma covered by squamous epithelium were found in 9 patients (27.3%). HGD and/or IMC were eradicated in 17 patients (eradicated group) and persisted in 16 patients (persistent group). In the persistent group, grade and architecture were unchanged after PDT in 62.5% and 87.5% of patients, respectively. The persistent group was characterized by: 1) a more frequent papillary architecture (P < 0.05), and 2) a diffuse distribution of the neoplasms on pre-PDT biopsies (P = 0.05). Singularly, the persistent neoplastic lesions were observed in the distal esophagus (P < 0.05). A systematic histopathologic evaluation allowed us to draw attention to the fact that distally located and papillary-type neoplasia seem resistant to PDT. The higher than expected incidence of buried residual neoplastic epithelium should also be emphasized since it represents a risk for undetected growth of malignancy.

Mediastinal epithelioid hemangioendothelioma resected by hemi-plastron window technique.

We report a case of epithelioid hemangioendothelioma arising from the left brachiocephalic vein in the anterior superior mediastinum of a 41-year-old man. The tumor was resected by local excision using a novel approach, the "hemi-plastron window" technique. The patient had an uneventful postoperative course and no recurrence of tumor 28 months after surgical treatment. We describe this surgical approach and discuss its advantage for cervicothoracic tumors.

Pathologic spectrum and prognostic significance of underlying liver disease in hepatocellular carcinoma.

Although controversy persists about the influence of cirrhosis on the incidence of portal vein invasion and other prognostic indicators of recurrence and survival (e.g., histologic grade, mitotic activity, multiplicity), it is clear that the degree of cirrhosis is important for the long-term survival of patients with HCC. Multicentricity is especially important because it reflects the field carcinogenesis associated with viral hepatitis and particularly chronic HCV infection [59]. A better understanding of the different mechanisms linked to tumor recurrence will help select the best candidates for curative surgery and help tailor adjuvant therapy, such as interferon therapy, to each patient [60]. Finally, the importance of vascular invasion, number of tumors, and tumor size of HCCs in addition to the effect of fibrosis has led Vauthey et al [20] to propose a simplified staging of HCC with better prognostication of survival.

EUS-guided photodynamic therapy of the pancreas: a pilot study.

BACKGROUND: Photodynamic therapy of pancreatic cancer by using percutaneously placed light catheters has been reported. The feasibility and safety of EUS-guided photodynamic therapy of the pancreas was studied in a porcine model. METHODS: After injection of porfimer sodium, a 19-gauge needle was inserted into the pancreas, the liver, the spleen, and the kidney under EUS guidance. A small diameter quartz optical fiber was passed through the EUS needle and used to illuminate the tissue with laser light. The tissue response to photodynamic therapy was examined. RESULTS: Localized tissue necrosis was achieved in all organs, without significant complication. There was no significant difference in inflammation induced by photodynamic therapy within the various organs. CONCLUSIONS: EUS-guided photodynamic therapy is a safe and simple technique that can induce small areas of focal tissue ablation within the liver, the pancreas, the kidney, and the spleen, and potentially could be used to treat a variety of benign and malignant conditions.

Endoscopic mucosal resection for gastric epithelial neoplasms: a study of 39 cases with emphasis on the evaluation of specimens and recommendations for optimal pathologic analysis.

Endoscopic mucosal resection of gastric neoplasms is a curative technique that avoids surgery and its potential complications. Infrequently performed in the West, the limitations, pitfalls and challenges provided by this new therapeutic modality are not well known by general surgical pathologists. We evaluated a series of 39 endoscopic mucosal resections and assessed the correlation between original biopsies and final diagnoses, depth of excision, status of deep and lateral margins, artifactual changes and recurrence rate. The tumors consisted of 24 intramucosal carcinomas, six high-grade dysplasias, eight low-grade dysplasias and one submucosal invasive carcinoma. The preresection diagnoses corresponded to the final evaluation in 63% of the cases with previous biopsies. In 37% of the cases, the biopsies under-diagnosed the neoplasia. The rate of positive margins was 38%. Iatrogenic changes, that is, intramucosal hemorrhage and electrodiathermic burn, were noted in 44% of the cases but hindered the pathologic evaluation in only 10% of the cases. Persistence or recurrence was observed in only seven cases and there was no progression to advanced adenocarcinoma. Based on our experience, we offer some recommendations in order to provide optimal pathologic analysis of endoscopic mucosal resection specimens.