Squamous cell carcinoma after radiofrequency ablation for Barrett's dysplasia.

Barrett's oesophagus (BO) is a usually indolent condition that occasionally requires endoscopic therapy. Radiofrequency ablation (RFA) is an effective endoscopic treatment for high grade dysplasia (HGD) and intramucosal cancer in BO. It has a good efficacy, durability and safety profile although complications can occur. Here we describe a case of RFA in a patient with high grade dysplasia. Although the response to treatment was initially very good with the development of neosquamous epithelium, the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology, histology and immunohistochemistry. Sanger sequencing confirmed that the original HGD and the squamous cell cancer (SCC) were derived from separate clonal origins. The report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated.

[Neoadjuvant therapy in the upper gastro-intestinal tract. Modern strategies for Barrett's cancer]. / Neoadjuvante Therapie im oberen Gastrointestinaltrakt. Aktuelle Konzepte beim Barrett-Karzinom.

While primary surgical resection with systematic lymphadenectomy remains the treatment of choice for locoregional Barrett's cancer, neoadjuvant chemotherapy is an increasingly accepted treatment modality for patients with locally advanced tumors and patients with extensive lymphatic spread. In contrast to neoadjuvant radiochemotherapy preoperative chemotherapy alone does not seem to increase peri-operative complications and mortality. Responders to pre-operative treatment clearly have a survival advantage as compared to those who do not respond. The use of positron emission tomography to measure changes in glucose metabolism of the primary tumor can predict response early after initiation of neoadjuvant chemotherapy and thus help to select patients who will or will not benefit from this approach. The best treatment strategy for non-responders to neoadjuvant therapy remains to be defined.

Early experience with radiofrequency energy ablation therapy for Barrett's esophagus with and without dysplasia.

Radiofrequency (RF) ablation using the HALO(360) system combined with proton pump inhibitor (PPI) therapy is a new treatment for Barrett's esophagus (BE). We assessed the safety and effectiveness of this combination therapy at a community-based, BE referral center. After symptom evaluation, endoscopy and histologic assessment, esophageal motility, pH monitoring on PPI, computed tomography, endoscopic ultrasonography and mucosal resection for nodules, we performed HALO(360) ablation followed by twice daily PPI and 3-monthly surveillance for up to 12 months. If metaplasia or dysplasia were present at follow-up, the patients received a second ablation. Thirteen patients (12 male) were treated, three with high-grade dysplasia, four with low-grade and six with non-dysplastic intestinal metaplasia. The mean baseline BE length was 6 cm (range 2-12); nine patients had an hiatal hernia and two had a prior fundoplication. Esophageal pH < 4.0 for < 4% of time was achieved only in 5/13 patients. A mean of 1.4 ablation sessions were performed, without serious adverse events or strictures. Complete eradication of BE was achieved in 6/13 (46%) patients. The mean endoscopic surface regression was 84% (from a mean length of 6 +/- 1 cm to 1.2 +/- 0.5 cm, P < 0.001). Complete elimination of dysplasia was achieved in 5/7 (71%) patients. Ablation efficacy was better in those patients who had maximal pH control (P < 0.05). HALO(360) ablation of BE with or without dysplasia is safe, well-tolerated and effective in the community setting. Follow-up ablation further reverses residual BE or dysplasia.

[A case of Barrett's esophageal cancer showing good response to combined chemotherapy with TS-1, CDDP and radiotherapy].

The patient was a 69-year-old man who, during a routine health examination, was found to have irregular mucosa in the lower esophagus, which was subsequently diagnosed by endoscopy as Barrett's esophagus. Endoscopic ultrasonography led to the diagnosis of advanced esophageal cancer with a depth of invasion corresponding to T2. While surgery was indicated, it was not considered feasible because of pleural adhesions due to old tuberculosis. Therefore, chemotherapy with TS-1 at the dose of 80 mg/day (4-week therapy followed by a 2-week withdrawal period) and CDDP at the dose of 3 mg/day (4-week of 5-day therapy followed by a 2-day withdrawal period) was instituted, followed 3 weeks later by the addition of radiotherapy with 1.8 Gy/day (5 times/week). Follow-up endoscopy revealed evident reduction in the lesion size 73 days after the start of TS-1 therapy, and complete disappearance of the lesion 185 days after the start of therapy. Grade 1 leukopenia was the only adverse effect of TS-1 noted in the patient. Treatment of Barrett's esophageal cancer is often conducted in accordance with the principles of treatment of esophageal squamous cell carcinoma, and surgical resection represents the most effective treatment. On the other hand, there have been no reports of effective adjuvant therapy. Based on our experience, the therapeutic strategy employed in this patient is considered to offer promise for the treatment of Barrett's esophageal cancer.

Investigation into the thermal distribution of microwave helical antennas designed for the treatment of Barrett's oesophagus.

A set of helical microwave antennas was designed to investigate their potential use in thermal therapy of Barrett's oesophagus. The antennas had a diameter of up to 3.3 mm and various lengths between 20 and 37 mm; these were designed to operate at 915 MHz. Sets of polytetrafluoroethylene (PTFE) formers were constructed to improve the repeatability and reproducibility of the helix manufacture. Small diameter copper wire was wound over the formers and connected to the coaxial cable at the inner and outer conductor junctions. The power deposition profiles of the antennas were measured in a muscle-equivalent phantom using an infrared camera. The effects of antenna length and coil spacing were characterized. It was observed that uniform temperature profiles along the antenna length were achieved with a length of wire of 99 mm +/- 2 mm. The effective heating length (length of the antenna that exhibits > 50% of the maximum temperature rise) was comparable to the antenna length. The radial penetration depth of 50% of the antenna surface temperature for the optimum 20 mm antenna was 2.5 mm from the antenna outer surface.

Prognostic significance and effect of chemoradiotherapy on microvessel density (angiogenesis) in esophageal Barrett's esophagus-associated adenocarcinoma and squamous cell carcinoma.

Previous studies have shown that intratumoral microvessel density (IMD) correlates with clinical outcome in a variety of human neoplasms, such as those that arise in the breast, colon, and stomach, suggesting that angiogenesis is important in cancer progression. The aims of this study were to evaluate the prognostic utility of IMD in esophageal Barrett's-associated adenocarcinoma (AdCa) and squamous cell carcinoma (SCC), and to determine the effect of preoperative chemoradiotherapy (chemrad) on this process. Tissue sections of tumor from 67 patients with esophageal carcinoma (45 with Barrett's-associated AdCa, 22 with SCC) were stained with the vascular marker CD31. The IMD was calculated by evaluating at least 5 different 200 x fields of tumor hot spot areas to obtain the mean microvessel count (MVC). The data then were correlated with the clinical and pathological features, chemrad status, and patient survival. The MVC was significantly higher in AdCa (143 +/- 63.2) compared with SCC (77.2 +/- 38.6, P = 0.0001). In AdCa, no correlation was noted between the MVC and any of the clinical or pathological features, including chemrad status. In contrast, in SCC, a statistically significant higher MVC was detected in patients who did not receive chemrad (97.2 +/- 37.3) compared with those who did (48.3 +/- 15.9, P = .002) and in tumors that were larger in size (P = .02). However, the MVC did not correlate with survival in either AdCa or SCC (P > .05). The degree of angiogenesis is not a significant prognostic indicator in either esophageal AdCa or SCC. Preoperative chemrad has a positive effect on reducing the degree of angiogenesis in esophageal carcinoma, particularly SCC.

Pathologic prognostic factors in Barrett's associated adenocarcinoma: a follow-up study of 96 patients.

BACKGROUND: The objective of this study was to evaluate a variety of histologic features, some of which to our knowledge have never been evaluated in Barrett's-associated adenocarcinoma (BAd) (such as Crohn's-like lymphoid reaction and peritumoral lymphoid response) in patients with and without preoperative neoadjuvant chemotherapy combined with radiotherapy (chemrad) to determine their prognostic significance in these two groups of patients. METHODS: Tumor sections from 96 patients (83 males and 13 females; mean age, 62 years) with resected BAd (61 with chemrad and 35 without chemrad) were evaluated for numerous histologic features such as pathologic stage according to the American Joint Committee on Cancer TNM staging system, peritumoral lymphoid infiltrate, Crohn's-like lymphoid reaction, and degree of post chemrad residual tumor and correlated with the preoperative chemrad status and with survival (mean follow-up, 23 months). RESULTS: By univariate analysis, older patient age (P = 0.02), higher pathologic stage (P = 0.02) (including depth of invasion and lymph node status), infiltrative growth pattern (P = 0.05), perineural invasion (P = 0.05), vascular invasion (P = 0.04), and the absence of a peritumoral lymphoid infiltrate (P = 0.04) were associated with shortened survival in the entire cohort and in patients without chemrad, with the exception of infiltrative growth pattern (P = 0.1 in the nonchemrad group only). Higher stage was the only feature associated with decreased survival in the chemrad group. Subcategorization of lymph nodes according to the number involved with metastases (fewer than four, four to seven, and greater than seven) had no further effect on prognosis. However, subcategorization of T1 tumors into Tla and T1b did influence prognosis in a negative manner. Using multivariate analysis, only older patient age (P = 0.005) and the absence of a peritumoral lymphoid infiltrate (P = 0.05) were statistically associated with poor survival independent of stage. In addition, perineural invasion (P = 0.07) showed a trend toward shortened survival in patients with this feature. Preoperative chemrad had no effect on survival in this retrospective nonrandomized cohort of patients. CONCLUSIONS: This study confirms the strong prognostic usefulness of the TNM staging system in patients with resected BAd, even in those patients who received preoperative chemrad. In addition, older patient age, the absence of a peritumoral lymphoid infiltrate, and possibly perineural invasion correlate with poor survival independent of pathologic stage in patients with these tumors.