Masafumi Oya

Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.

Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform–pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and &agr;-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and &agr;-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and &agr;-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform–pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1–239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.

Long-term follow-up study of patients with gastric adenomas with malignant transformation. An immunohistochemical and histochemical analysis.

Background. Little is known about the changes in the immunohistochemical and histochemical characteristics that take place during the malignant transformation of gastric adenoma (GA).

Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation

A 70‐year‐old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co‐existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace‐like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma–carcinoma sequence. Copyright

Gastrointestinal stromal tumor of the stomach: How to manage?

Gastrointestinal stromal tumor (GIST) is one of the most common malignant mesenchymal tumors of the stomach. Prognosis of this disease is related to tumor size and mitotic activity and early diagnosis is the only way to improve it. Diagnosis of GIST always requires histological and immunohistochemical confirmation as no imaging modalities can diagnose it conclusively. Endoscopic forceps biopsy results are frequently negative. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a technique which allows tissue samples to be obtained with minimal risks and is accurate in the diagnosis of GIST. From the point of view of the endoscopist, aggressive use of EUS-FNA is the only promising way to allow early diagnosis and early treatment of this disease.

Metastasizing intramucosal gastric carcinomas. Well differentiated type and proliferative activity using proliferative cell nuclear antigen and Ki-67.

Background. Recently, endoscopic surgery for small superficial gastric carcinomas has become increasingly more challenging, and the treatment criteria remain controversial.

Endoscopic submucosal dissection by using a grasping-type scissors forceps: a preliminary clinical study (with video).

BACKGROUND Endoscopic submucosal dissection (ESD) with a knife is a technically demanding procedure associated with a high complication rate. The shortcoming of this method is the difficulty of fixing the knife to the target lesion. It can lead to an unexpected incision and result in major complications, such as perforation and bleeding. To reduce the risk of complications related to ESD, we developed a new grasping-type scissors forceps (GSF), which can grasp and incise the targeted tissue by using electrosurgical current. OBJECTIVE To evaluate the efficacy and safety of ESD by using GSF for the removal of gastric neoplasms in human beings. DESIGN Prospective, uncontrolled, single center. SETTING Department of Gastroenterology, Aso Iizuka Hospital, Iizuka, Japan. PATIENTS Four patients with early gastric neoplastic lesions. INTERVENTIONS After marking and injection of a solution into the submucosa, the lesion was separated from the surrounding normal mucosa by complete incision around the lesion by using the GSF. A piece of submucosal tissue was grasped and cut with the GSF by using electrosurgical current to achieve submucosal excision. MAIN OUTCOME MEASUREMENT Technical success and complications. RESULTS All lesions were treated easily and safely, without any unexpected incisions. No delayed hemorrhage and perforation occurred. An en bloc resection and a negative resection margin was obtained in all cases. LIMITATIONS The small number of patients and an uncontrolled study. CONCLUSIONS ESD with GSF appeared to be an easy, safe, and technically efficient method for resecting GI neoplasms.

A new approach: endoscopic submucosal dissection using the Clutch Cutter® for early stage digestive tract tumors.

Endoscopic submucosal dissection (ESD) is accepted as minimally invasive therapy for early stage digestive tract tumors. It has allowed the achievement of histologically curative en-bloc resection of early stage digestive tract tumors regardless of size, including the resection of previously non-resectable tumors. Although numerous electrosurgical knives have been developed for ESD, technical difficulties and high complication rates (bleeding and perforation) have limited their use worldwide. Furthermore, conventional ESD usually needs several devices for each session. We developed the Clutch Cutter® (CC), which can grasp and incise the targeted tissue using electrosurgical current, to resolve such ESD-related problems. The ESD procedure using the CC is as follows: after marking using the CC and the injection of a solution into the submucosa, the lesion is separated from the surrounding normal mucosa by complete incision around the lesion using the CC. A piece of submucosal tissue is grasped and cut with the CC using electrosurgical current to achieve submucosal exfoliation. Intraoperative bleeding is also treated by the CC. Reported clinical studies showed that ESD using the CC is a safe, simple, easy-to-learn, technically efficient (en-bloc resection rate 100%), and a single-device method for the dissection of early stage digestive tract tumors. This new approach is promising to become the worldwide method of choice for early stage digestive tract tumors because it is technically simple and safe to perform.

ENDOSCOPIC SUBMUCOSAL DISSECTION USING A GRASPING-TYPE SCISSORS FORCEPS FOR EARLY GASTRIC CANCERS AND ADENOMAS

Aim:  To reduce the risk of complications related to endoscopic submucosal dissection (ESD) using knives, we developed a new grasping‐type scissors forceps (GSF) that can grasp and incise the target tissue using electrosurgical current. The aim of the present study was to evaluate the efficacy and safety of ESD using GSF for the removal of early gastric cancers and adenomas.

Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes

Abstract Objective. The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. Materials and methods. The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. Results. Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. Conclusion. The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Expressions of cell-cycle regulatory gene products in conventional gastric adenomas: possible immunohistochemical markers of malignant transformation.

In 54 lesions of gastric adenomas consisting of 31 low-grade adenomas (LGAs) and 23 high-grade adenomas (HGAs), 28 intramucosal carcinomas (IMCs), and 23 carcinomas invading the submucosa (SMCs), the expression of cell-cycle regulatory gene products (p53, p21/waf1, p27/kip1, and Ki-67) was studied using immunohistochemical techniques. Several lesions were also analyzed by the fluorescence in situ hybridization method. The overexpression of p53 was found in no LGAs and in 9% of HGAs, whereas a considerable number of cases showed an overexpression in IMCs (39%) and SMCs (43%). A reduced expression of p21/waf1 was present in only 4% of HGAs. Superficial eccentric positivity was present in all LGAs and 74% of HGAs, whereas it was present in 46% of IMCs and 4% of SMCs. P53-positive and p21/waf1-negative lesions, which were supposed to have a mutated p53 gene, were observed in no LGAs, in 4% of HGAs, in 11% of IMCs, and in 26% of SMCs. The expression of cyclin E was more frequently present in carcinomas than in adenomas. However, no high expression of cyclin E was observed among the adenomas. A reduced expression of p27/kip1 was encountered more frequently in carcinoma than adenoma. By a semiquantitative evaluation comparing adenoma and carcinoma in the same stomach, the increased degrees of both p21/waf1 and cyclin E were highlighted. A chromosome gain was detected among 7% of the adenomas and 85% of the carcinomas. In conclusion, the expressions of p53, p21/waf1, p27/kip1, and cyclin E were considered to be of great value for estimating the dysplastic progression of gastric adenomas. Especially, various aspects of protein expression, including its distribution and semiquantitative evaluation of positive cells, and a combined analysis with several proteins, may thus be useful as possible markers of dysplastic evolution in gastric adenomas.