Endoscopic submucosal dissection in large sessile lesions of the rectosigmoid: learning curve in a European center.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) in the colorectum is not currently a standard procedure. Few data are available from the Western world. The aim of the present study was to report on the first experiences and the learning curve of colorectal ESD in a European center. PATIENTS AND METHODS: A total of 82 rectosigmoid lesions were referred for ESD. Lesion characteristics, resection rates, procedure times, complications, and recurrences were recorded prospectively. Results were compared between three consecutive study periods in order to determine the learning curve. RESULTS: Lesions were located in the rectum (86.6 %) and the sigmoid colon (13.4 %). Median diameter was 45.5 mm. Lesions were of Paris type 0-Is with pit pattern type V (n = 8), 0-IIa (n = 33), 0-IIa + Is (n = 36), and 0-IIa + IIc (n = 5). The malignancy rate in these groups was 100 %, 0 %, 14 %, and 20 %, respectively. ESD was possible in 76 lesions (92.7 %). En bloc resection rate and R0 resection rate were 81.6 % and 69.7 %, respectively. Median procedure time was 176 minutes. Between the three consecutive study periods, en bloc resection rate increased (60.0 %, 88.0 %, 96.2 %), R0 resection rate increased (48.0 %, 76.0 %, 84.5 %; P < 0.001), and procedure time decreased (200, 193, 136 minutes; P = 0.027). The perforation and bleeding rates were 1.3 % and 7.9 %, respectively. Recurrence risk was 0 % after R0 en bloc resection and 41.7 % after piecemeal resection (P < 0.05). Median follow-up was 23.6 months. CONCLUSIONS: In the European setting, ESD in the distal colon is feasible with acceptable complication risks. Resection rates were not as high as those from Japanese studies; however, a clear learning curve could be shown. Colorectal ESD needs to be further evaluated, particularly in Europe where ESD experience is low.

Endoscopic submucosal dissection in gastric neoplasia - experience from a European center.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a promising technique for the resection of early gastric neoplasia. There are only a few data from the Western world to date. METHODS: Over a 7-year-period, 104 gastric lesions were treated with ESD in a European referral center, of which 91 were included in this study. A total of 66 lesions were early gastric cancer (EGC) and 25 were adenomas. Of the EGCs, 11 lesions (16.7 %) fulfilled the guideline criteria (EGC-GC) and 55 lesions (83.3 %) fulfilled the expanded resection criteria (EGC-EC) of the Japanese guidelines for the treatment of gastric cancer. RESULTS: ESD was technically possible in 85 lesions (93.4 %). In six lesions ESD was not possible due to non-lifting. En bloc resection rates for all lesions, ECGs-GC, ECGs-EC, and adenomas were 87.1 %, 100 %, 88.2 %, and 79.2 %, respectively. R0 en bloc resection rates were 74.1 %, 90 %, 68.6 %, and 79.2 %, respectively. Complications were: one perforation during piecemeal endoscopic mucosal resection of a lesion in which ESD was judged to be impossible (1.2 %); three clinically relevant bleedings (3.5 %); one gastric ischemia (1.2 %); and four strictures (4.7 %). No mortality was observed. There were five recurrences after piecemeal resection (50 %) compared with only one after en bloc resection (1.5 %; P < 0.05). The rate of recurrence for EGCs was 5.6 %, and this were seen exclusively after piecemeal resection. CONCLUSIONS: Our data show that ESD is a feasible technique in Europe even in patients with EGC according to the extended criteria. Resection rates are promising and complication rates are acceptable. Results are worse compared with large studies from Japan but still excellent regarding the learning curve of the method. ESD should be offered as the treatment of choice for early gastric neoplasia especially when en bloc resection cannot be performed with other resection techniques.

Cidofovir use in acyclovir-resistant herpes infection.

Herpes infections continue to be prevalent, especially in immunocompromised patients. Some of these patients will develop resistant HSV infections. Therefore, it is important to explore new treatment options. Animal studies have shown cidofovir to be effective in the treatment and prevention of HSV infections. Human data are limited, with only one randomized, double-blind, placebo-controlled trial performed to date. The results from this study look promising; however, due to the small sample size, a larger clinical trial is warranted. The human data available as case reports are suboptimal in the quality of reporting time frames for resolution of lesions/symptoms and outcomes of therapy. Another problem with the case report data is that the TK status of the herpes simplex isolates was not reported. This would have helped substantiate the acyclovir resistance seen in these patients. It was evident in these case reports that acyclovir resistance can be overcome, as acyclovir-resistant strains became sensitive following cidofovir therapy. This may be because TK(+) viruses have been shown to establish latency more readily than do TK(-) viruses. This pattern suggests that alternating between acyclovir and cidofovir therapies may provide a strategy to manage the emergence of alternatively acyclovir-sensitive and -resistant infections. At present, only the intravenous formulation of cidofovir is commercially available. Advantages of the intravenous formulation include weekly dosing and efficacy. Disadvantages are the complexity of administration and the adverse effect profile. The most common adverse effects with this formulation include nephrotoxicity manifested as proteinuria (12%), and increased creatinine (5%) and neutropenia (15%). Administration of probenecid and NaCl 0.9% hydration are used to reduce the incidence and severity of nephrotoxicity in patients who are receiving cidofovir. Probenecid also has toxicities, including nausea, vomiting, headache, fever, and flushing. The topical formulation of cidofovir looks promising for mucocutaneous HSV infection because it is usually undetectable in the blood following topical administration. Therefore, systemic adverse effects should be minimized. A cidofovir gel product (Forvade, Gilead Sciences) is currently being reviewed by the Food and Drug Administration for the treatment of refractory HSV. Ultimately, more controlled clinical studies are necessary to determine whether routine cidofovir use can be justified in patients with acyclovir-resistant HSV infection.