Toshiaki Hirasawa

Incidence of lymph node metastasis and the feasibility of endoscopic resection for undifferentiated-type early gastric cancer

BackgroundEndoscopic resection (ER) has been accepted as minimally invasive treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. It has already been determined which lesions in differentiated-type EGC present a negligible risk of lymph node metastasis, and ER is being performed for these lesions. In contrast, no consensus has been reached on which lesions in undifferentiated-type (UD-type) EGC present a negligible risk for lymph node metastasis, nor have indications for ER for UD-type EGC been established.MethodsWe investigated 3843 patients who had undergone gastrectomy with lymph node dissection for solitary UD-type EGC at the Cancer Institute Hospital, Tokyo, and the National Cancer Center Hospital, Tokyo. Seven clinicopathological factors were assessed for their possible association with lymph node metastasis.ResultsOf the 3843 patients, 2163 (56.3%) had intramucosal cancers and 1680 (43.7%) had submucosal invasive cancers. Only 105 (4.9%) intramucosal cancers compared with 399 (23.8%) submucosal invasive cancers were associated with lymph node metastases. By multivariate analysis, tumor size 21 mm or more, lymphatic-vascular capillary involvement, and submucosal penetration were independent risk factors for lymph node metastasis (P < 0.001, respectively). None of the 310 intramucosal cancers 20 mm or less in size without lymphatic- vascular capillary involvement and ulcerative findings was associated with lymph node metastases (95% confidence interval, 0–0.96%).ConclusionUD-type intramucosal EGC 20 mm or less in size without lymphatic-vascular capillary involvement and ulcerative findings presents a negligible risk of lymph node metastasis. We propose that in this circumstance ER could be considered.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer.

BACKGROUND AND STUDY AIM Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC. PATIENTS AND METHODS Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes. RESULTS The rates of en bloc and curative resection were 99.0% (102/103) and 82.5% (85/103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6%) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19-92 months) and 36.0 months (range 9-92 months), the 3-and 5-year overall mortality rates were 1.9% and 3.9%, respectively, and the 3-and 5-year overall disease-free survival rates were both 96.7%. CONCLUSIONS Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes.

THERAPEUTIC OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION OF UNDIFFERENTIATED-TYPE INTRAMUCOSAL GASTRIC CANCER WITHOUT ULCERATION AND PREOPERATIVELY DIAGNOSED AS 20 MILLIMETRES OR LESS IN DIAMETER

Aim:  The aim of the present study was to examine therapeutic outcomes of endoscopic submucosal dissection (ESD) of undifferentiated‐type intramucosal gastric cancer and the problems of diagnosis.

Sporadic nonampullary duodenal adenoma in the natural history of duodenal cancer: a study of follow-up surveillance.

OBJECTIVES:Although sporadic nonampullary duodenal adenoma (SNDA) is regarded as a precancerous lesion, its natural course is uncertain. The aim of this study was to evaluate the risk of development of adenocarcinoma in SNDA lesions initially diagnosed as showing low-grade dysplasia (LGD; category 3) or high-grade dysplasia (HGD; category 4.1).METHODS:We analyzed 68 SNDAs, diagnosed based on initial and subsequent biopsies, in 66 consecutive patients. Of these, 46 (43 LGD lesions, 3 HGD lesions) were followed up for ≥6 months without treatment (mean 27.7±16.9 months; range 6–72 months), including 8 lesions that were eventually resected during follow-up. Sixteen lesions (eight LGD lesions, eight HGD lesions) were resected immediately, either endoscopically or surgically, and six lesions were excluded because of a short follow-up (<6 months). The histopathological diagnoses and macroscopic changes were evaluated.RESULTS:Among the 43 LGD lesions followed up for ≥6 months, 34 (79.1%) showed no histopathological changes during follow-up, whereas the remaining 9 (20.9%) showed progression to HGD, including 2 (4.7%) that progressed eventually to noninvasive carcinoma (category 4.2). Macroscopically, 76.7% (33 of 43) of the LGD lesions showed no notable changes in size, 16.3% (7 of 43) became undetectable, 4.7% (2 of 43) reduced in size, and 2.3% (1 of 43) became larger in size. In contrast, all the three HGD lesions that were followed up for ≥6 months remained unchanged histologically, based on biopsy, and showed no notable macroscopic changes, although one of these HGD lesions resected endoscopically revealed evidence of noninvasive carcinoma. Although we diagnosed all lesions as HGD from biopsy samples, a high percentage of cancers (54.5%, 6 of 11) were diagnosed from resected specimens. A multivariate analysis identified HGD diagnosed at first biopsy and a lesion diameter of ≥20 mm as being significantly predictive of progression to adenocarcinoma.CONCLUSIONS:LGD lesions show a low risk of progression to adenocarcinoma, but some risk of progression to HGD, which warrants careful follow-up biopsy. However, HGD lesions and large SNDAs ≥20 mm in diameter show a high risk of progression to adenocarcinoma. Therefore, they should be treated immediately.

Diagnosis of undifferentiated type early gastric cancers by magnification endoscopy with narrow-band imaging.

Background and Aims:  The diagnostic use of magnification endoscopy with narrow‐band imaging (ME‐NBI) to assess histopathologically undifferentiated‐type early gastric cancers (UD‐type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME‐NBI images and histopathological findings in UD‐type EGCs.

Laparoscopic endoscopic cooperative surgery.

Laparoscopic and endoscopic cooperative surgery (LECS) is a newly developed concept for tumor dissection of the gastrointestinal tract that was first investigated for local resection of gastric gastrointestinal stromal tumors (GIST). The first reported version of LECS for GIST has been named ‘classical LECS’ to distinguish it from other modified LECS procedures, such as inverted LECS, a combination of laparoscopic and endoscopic approaches to neoplasia with a non‐exposure technique (CLEAN‐NET), and non‐exposed endoscopic wall‐inversion surgery (NEWS). These modified LECS procedures were developed for dissection of malignant tumors which may seed tumor cells into the abdominal cavity. While these LECS‐related procedures might prevent tumor seeding, their application is limited by several factors, such as tumor size, location and technical difficulty. Currently, classical LECS is a safe and useful procedure for gastric submucosal tumors without mucosal defects, independent of tumor location, such as proximity to the esophagogastric junction or pyloric ring. For future applications of LECS‐related procedures for other malignant diseases with mucosal lesions such as GIST with mucosal defects and gastric cancer, some improvements in the techniques are needed.

CURRENT STATUS OF TRAINING FOR ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTRIC EPITHELIAL NEOPLASM AT CANCER INSTITUTE HOSPITAL, JAPANESE FOUNDATION FOR CANCER RESEARCH, A FAMOUS JAPANESE HOSPITAL

Aim:  Endoscopic submucosal dissection (ESD) is relatively difficult compared with endoscopic mucosal resection (EMR), thus, proper training is essential for the safe performance of the procedure. The aim of this study is to clarify the current status of training for ESD for gastric epithelial neoplasm by following the performance of 13 preceptees.

Lymph node metastasis from undifferentiated-type mucosal gastric cancer satisfying the expanded criteria for endoscopic resection based on routine histological examination

A 58-year-old woman was found to have a 45-mm abdominal mass adjacent to the pancreas on screening ultrasonography, and subsequent esophagogastroduodenoscopy revealed a small gastric cancer (13 mm in diameter). We initially performed endoscopic submucosal dissection (ESD), and routine histological examination of the specimen sectioned at 2-mm intervals revealed a poorly differentiated adenocarcinoma and signet ring cell carcinoma confined to the mucosa without lymphatic-vascular capillary involvement or ulceration. These findings satisfied the expanded criteria for ESD we reported recently. We next performed laparoscopic excisional biopsy of the abdominal mass, and histological examination with immunohistochemical staining revealed a metastatic lymph node (LN) resulting from the gastric cancer. Distal gastrectomy with extended lymphadenectomy was then performed and histological examination indicated no residual cancer cells or any additional LN metastases. After the above-described clinical course, further analysis was conducted because of the highly unusual nature of this case; 60 additional deep-cut sections from the resected specimen were performed, with one section showing lymphatic involvement in the mucosa on hematoxylin and eosin staining. This case suggests practical limitations in determining lymphatic involvement through routine histological examination, which may not always be able to detect LN metastasis.

Endoscopic mucosal resection and endoscopic submucosal dissection for en bloc resection of superficial pharyngeal carcinomas

BACKGROUND AND STUDY AIM Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are being used increasingly to treat superficial oropharyngeal and hypopharyngeal carcinomas. The aim of this study was to clarify whether ESD provided better results than EMR for en bloc and complete resection of superficial pharyngeal carcinomas. PATIENTS AND METHODS A total of 76 superficial pharyngeal carcinomas in 59 consecutively treated patients were included. Patients underwent either conventional EMR (using a transparent cap or strip biopsy) (n = 45 lesions) or ESD (n = 31 lesions) between October 2006 and January 2011. The rates of en bloc resection, complete resection (defined as en bloc resection with tumor-free margins), major complications, and local recurrence were evaluated retrospectively as the therapeutic outcomes. RESULTS ESD yielded significantly higher rates of both en bloc and complete resection compared with EMR (en bloc 77.4 % [24/31] vs. 37.8 % [17/45], P = 0.0002; complete 54.8 % [17/31] vs. 28.9 % [13/45], P = 0.0379). ESD was more frequently complicated by severe laryngeal edema (4/21 [19.0 %] vs. 1/31 [3.2 %], P = 0.1446) and was also more time-consuming (124.9 ± 65.1 minutes vs. 57.2 ± 69.6 minutes; P = 0.0014). Local recurrence was observed more often after EMR than after ESD (3/45 [6.7 %] vs. 0/31 [0 %]), although this difference did not reach statistical significance (P = 0.2658). CONCLUSIONS ESD appears to be a superior method of endoscopic resection of superficial pharyngeal carcinomas for achieving both en bloc and complete resection, although these benefits were also associated with a higher incidence of complications and a significantly longer procedure time. Large prospective studies are needed to compare ESD with conventional EMR for superficial pharyngeal carcinomas.

Helicobacter pylori-negative gastric cancer: Characteristics and endoscopic findings

Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions and eradication therapy. However, some reports have described cases of H. pylori‐negative gastric cancers (HpNGC), and the prevalence was 0.42–5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD‐type) is more frequent than the differentiated type (D‐type). The UD‐type is mainly signet ring‐cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D‐type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor‐like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patients quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.