Kenro Kawada

ANGIOGENESIS IN SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA : MAGNIFYING ENDOSCOPIC OBSERVATION AND MOLECULAR ANALYSIS

Observations of esophageal squamous cell carcinoma using magnifying endoscopy have now been carried out extensively and, as a result, it has become clear that the morphology of the microvessels evident at the tumor surface reflects the depth of tumor invasion. In M1 and M2 cancer, the surface microvasculature reveals dilation and elongation of the intrapapillary capillary loops (IPCL). However, at this stage, some immature capillaries resembling IPCL also arise inside the tumor and, therefore, the view of the microvasculature should be described as one showing ‘intermixing of modified IPCL and IPCL‐like immature capillaries (IPCL‐like abnormal capillary)’. As cancer invades into the muscularis mucosa (M3 or deeper), an obviously dilated and irregularly branched tumor‐specific vasculature, more accurately described as ‘neovasculature’, can be observed. From our magnifying endoscopy observations and studies of the molecular profile of early esophageal cancer, we conclude that two major angiogenic steps exist in precancerous and M3 lesions in the early phase of cancer progression. In addition, it is now possible to study cell morphology using an endocytoscope with a much higher magnification (×400–×1000) than magnifying endoscopes currently on the market. The histology revealed in this way may reduce the need for conventional biopsy histology in the future.

Palisade vessels as a new histologic marker of esophageal origin in ER specimens from columnar-lined esophagus.

It is difficult for surgical pathologists to determine the origin of tissues in samples taken from the columnar-lined esophagus (CLE) or stomach by biopsy or endoscopic resection (ER) on the basis of histologic examination alone. We examined histopathologically a single section (5 to 22 mm in size; mean, 12 mm) from each of 66 cases of CLE (36 short segments, 30 long segments) from German patients with reference to 3 histologic markers of esophageal origin: esophageal glands proper and/or ducts, squamous islands, and double muscularis mucosae, all of which had been reported previously, and palisade vessels as a new histologic parameter as well. Palisade vessels were defined histologically as veins >100 &mgr;m in size in and above the original muscularis mucosae. Esophageal glands proper and/or ducts, squamous islands, and double muscularis mucosae were seen in 33%, 18%, and 71% of the specimens, respectively. Palisade longitudinal vessels were observed in 78% and 63% of specimens of short-segment and long-segment CLE, respectively. Palisade vessels were never seen in ER specimens from the stomach or in the middle esophagus and stomach among control autopsy specimens. At least 1 of these 4 markers was seen in 88% of the sections. Therefore, ER specimens were confirmed to originate from CLE in 88% of single histologic sections of CLE on the basis of histologic examination alone.

ENDOCYTOSCOPIC OBSERVATION OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA

The endocytoscopy system (ECS), adapted for clinical use in 2003, is an ultra‐high‐power magnifying endoscope that allows observations at the cell level. ECS is based on the technology of light‐contact microscopy. The most evident use of ECS is for real‐time, high‐resolution diagnosis of nuclear abnormalities, mainly in patients with esophageal cancer. Up to now, three different types of ECS have been available. This diagnostic tool makes it possible to omit histological examination of biopsy samples in approximately 84% of esophageal squamous cell carcinoma, as evidence for both an increase of cell density and nuclear abnormalities is considered to be convincing proof that a lesion is malignant. Here we describe the features of ECS and the background that led to its development, and review the published literature pertaining to the observation of esophageal neoplasms using ECS.

Current status and limitations of the newly developed endocytoscope GIF‐Y0002 with reference to its diagnostic performance for common esophageal lesions

Objectives:  To investigate both neoplastic and non‐neoplastic lesions of the esophagus and to clarify the features of the surface cell morphology using a newly developed endocytoscope, the GIF‐Y0002.

Internal Pressure of the Conduit during Endoscopy on the Day after Esophagectomy

Background: In gastrointestinal surgery, anastomosis can result in various complications. Anastomosis is evaluated using classical examinations. The most reliable one is endoscopy, which provides direct information on the anastomosis and conduit. But the influence of endoscopy on anastomosis is uncertain. Methods: The internal pressure of a graft during endoscopy was measured in 36 patients who received esophagectomy, by utilizing the decompression tube which was inserted into the graft during operation. We filled the tube with water and measured the maximum water level in a centimeter water column. All examinations were routinely performed on the day after operation, and thin endoscopes were selected for reducing the stress. Results: The internal pressure before endoscopy ranged from 6 to 20 cm H2O, and during endoscopy ranged from 9 to 27 cm H2O. The difference in the internal conduit pressure in each patient ranged from 1 to 9 cm H2O. There was no increase in complications caused by endoscopy, including anastomotic leakage. Conclusion: This study is the first to report changes in internal pressure due to the endoscope by direct measurement. The pressure gradient observed was below the physiological pressure during swallowing. These results suggest that endoscopy is a safe examination even after surgery.

Subcutaneous reconstruction using ileocolon with preserved ileocolic vessels following esophagectomy or in esophageal bypass operation.

Background: When forming an esophageal substitute with an ileocolon in esophageal reconstruction with cervical anastomosis, the ileocolic vessels should be divided in many cases and this may be followed by the occurrence of poor blood circulation in the pulled-up substitute. Methods: Twenty-two consecutive esophageal reconstructions using an all-main-vessel-preserving ileocolon had been performed in the past 4 years and we evaluated the usefulness of this surgical modality. Results: In every case, the extension length of the ileocolon was sufficient for esophageal reconstruction. There were no serious surgical complications concerning the esophageal substitutes such as necrosis of the pulled-up ileocolon. Conclusions: Although it was thought that the surgical techniques shown here were possible only in selected patients, successful esophageal reconstructions were achieved with this new concept in 22 consecutive patients with various backgrounds. The procedures shown here are not new; however, the concept of using the all-main-vessel-preserving ileocolon as an esophageal substitute for every patient requiring esophageal reconstruction is new.

NEW ARGON PLASMA COAGULATION METHOD FOR SUPERFICIAL ESOPHAGEAL CARCINOMAS: ARGON PLASMA COAGULATION‐SUBEPITHELIAL ABLATION

Argon plasma coagulation (APC) has been introduced to the field of therapeutic endoscopy and is now widely used. A new ablation technique is herein proposed for the treatment of superficial esophageal carcinomas. According to this technique, after the initial ablation, we exfoliate the epithelium and then perform a second ablation (APC‐subepithelial ablation). APC is applied at a power/gas setting of 60 W and 2l min in the esophagus. The APC applicator is inserted through the working channel of the endoscope, and a transparent hood is then set at the tip of the endoscope. At first, lines are traced around the tumor. Next, the initial ablation is made in a uniform manner. A transparent hood is then attached to the ablated tumor and, thereafter, the epithelium is easily exfoliated. The muscularis mucosae are preserved. We next identify any remaining non‐uniform ablation areas and then a second ablation is made on those areas. To obtain a complete eradication of the mucosal and submucosal tissue, the endoscopic appearance of brownish subepithelial tissue following the secondary argon plasma irradiation after epithelial exfoliation with initial argon plasma irradiation is needed. The secondary ablation could thus safely ablate at the esophageal gland level. The procedure is minimally invasive and easy to apply. A total of 48 patients with superficial esophageal squamous cell carcinoma were treated between February 2000 and April 2006 (median follow up 46 months). One hundred and sixty one sessions were performed with no major complications (no bleeding, no perforation, and no stenosis). The technique is thus considered to be safe.

A newly developed continuous zoom-focus endocytoscope

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074. Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to × 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma. Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo. Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.

On endocytoscopy and posttherapy pathologic staging in esophageal cancers, and on evidence-based methodology.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the value of endocytoscopy to replace biopsy histology for squamous cell carcinoma and the clinical significance of posttherapy pathologic stage in patients with esophageal adenocarcinoma following preoperative chemoradiation; a short discussion of evidence‐based methodology is also included.

Osteoplastic bone metastasis in esophageal squamous cell cancer : report of a case

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient’s general condition.