Saburo Shikuwa

Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study

Objective: Endoscopic submucosal dissection (ESD) has the advantage over conventional endoscopic mucosa resection, permitting removal of early gastric cancer (EGC) en bloc, but long-term clinical outcomes remain unknown. A follow-up study on tumour recurrence and survival after ESD was conducted. Method: ESD was performed for patients with EGC that fulfilled the expanded criteria: mucosal cancer without ulcer findings irrespective of tumour size; mucosal cancer with ulcer findings ⩽3 cm in diameter; and minute submucosal invasive cancer ⩽3 cm in size. 551 patients with 589 EGC lesions were enrolled. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6–89 months (median, 30 months). The main outcome measures were resectability (en bloc or piecemeal resection), and curability (curative or non-curative). Complications were assessed, and factors related to each were analysed statistically. The overall and disease-free survival rates were estimated. Results: En bloc resection was achieved in 94.9% (559/589), and larger lesions were at higher risk of piecemeal resection. 550 of 581 lesions (94.7%) were deemed to have undergone curative resection. En bloc resection was the only significant contributor to curative ESD. Patients with non-curative resection developed local recurrence more frequently. The 5-year overall and disease-specific survival rates were 97.1% and 100%, respectively. Conclusion: Precise assessment of curability with successful one-piece resection may reduce tumour recurrence after ESD. The prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted.

Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma

BACKGROUND Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. However, postprocedure stricture is common after ESD for extensive tumors, and multiple endoscopic balloon dilation (EBD) is required for recalcitrant cases. OBJECTIVE To evaluate the effectiveness of oral prednisolone in controlling postprocedure esophageal stricture. DESIGN Retrospective study. SETTING Endoscopy department at a university hospital. PATIENTS Patients who underwent complete circular or semicircular ESD for esophageal squamous cell carcinoma involving more than three fourths of the lumen were treated with either pre-emptive EBD or oral prednisolone. INTERVENTION Preemptive EBD was started on the third day post-ESD and continued twice weekly for 8 weeks. Oral prednisolone was started at 30 mg/day on the third day post-ESD , tapered gradually, and then discontinued 8 weeks later. An additional EBD was performed on demand in both groups whenever dysphagia appeared. MAIN OUTCOME MEASUREMENT The incidence of esophageal stricture and number of EBD sessions required to relieve dysphagia. RESULTS Stricture at 3 months after ESD was found in 7 of 22 patients in the preemptive EBD group but only 1 of 19 in the oral prednisolone group (P < .05). The average number of EBD sessions required was 15.6 in the preemptive EBD group and 1.7 in the oral prednisolone group (P < .0001). After complete circular ESD, 32.7 EBD sessions were needed on average in the preemptive EBD group, whereas fewer were needed in the oral prednisolone group (P < .05). LIMITATIONS Nonrandomized study. CONCLUSIONS Post-ESD esophageal strictures were persistent even if treated preemptively with multiple EBD sessions, but oral prednisolone may offer a useful preventive option.

Clinicopathological factors associated with clinical outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) permits removal of colorectal epithelial neoplasms en bloc, but a substantial risk of procedure-related perforation has been reported. We sought to unravel the clinicopathological factors associated with the clinical outcomes of ESD for colorectal epithelial neoplasms in a large series. PATIENTS AND METHODS ESD was done in 278 patients with 292 colorectal tumors that fulfilled the inclusion criteria. The criteria for ESD were: lesion greater than 20 mm in size, lesion with fibrotic scarring, locally residual colorectal lesion, or invasive carcinoma with slight submucosal penetration. Resection was assessed as en bloc or piecemeal, complete (en bloc with tumor-free lateral and basal margins) or incomplete. Complications including perforation and bleeding were assessed, and factors related to each were analyzed using logistic regression. Patients underwent multiple follow-up endoscopic examinations (mean 4.6; median 4; range 2 - 9; total number 1010). RESULTS En bloc resection was achieved in 90.1 % of lesions (263/292) and resection was deemed to be complete in 233 (79.8 %). Right-side colonic location and the finding of fibrosis were the significant contributors to incomplete resection. Perforation was seen in 24 cases (8.2 %), and was associated with large tumor size and the presence of fibrosis. When the contributive factors for each were combined, the risks of incomplete resection and perforation were substantially increased. CONCLUSION The present study provides useful information for predicting risks for incomplete resection and complication in colorectal ESD.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer by indication criteria.

Background and Study Aims: Endoscopic submucosal dissection (ESD) can remove early gastric cancer (EGC) en bloc. We sought to assess the feasibility and efficacy of ESD and the clinical outcomes based on the indication criteria. Patients and Methods: 551 patients with 589 EGC lesions were divided into the guideline criteria group (elevated lesion ≤20 mm in diameter and depressed lesion ≤10 mm without ulceration) and the expanded criteria group (mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings ≤3 cm in diameter; and minute submucosal invasive cancer ≤3 cm in size). Results: En bloc, complete and curative resection were achieved in 98.6 and 93.0, 95.1 and 88.5, and 97.1 and 91.1%, for the guideline and expanded criteria lesions, respectively; the differences between the 2 groups were significant for each. The expanded criteria lesions were at significantly higher risk of ESD-associated bleeding and perforation. Overall survival was adequate irrespective of the indications, and the disease-specific survival rates were 100% in both. Conclusion: ESD for EGCs that met the expanded criteria was acceptable, though the resection rates and safety were decreased compared to those for the guideline criteria lesions.

Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma

BackgroundEndoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD.MethodsSeven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia.ResultsEn bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions.ConclusionsUse of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer

Heat shock proteins (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. We determined the expression of Hsp 70 and Hsp 40 in 81 gastric cancers. Immunoreactivities to Hsp 70 and Hsp 40 were detected in 67.9 and 22.2% of tumors, respectively. Immunohistochemical analysis showed enhanced Hsp 70 and Hsp 40 expression in gastric tumor tissue, relative to the surrounding normal tissue. Overexpression of Hsp 70 and Hsp 40 was also confirmed by immunoblotting. Among various clinicopathological parameters, low histopathological differentiation was associated with reduced expression of both proteins.

Recent insights into digestive motility in functional dyspepsia

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.

Clinical outcomes of endoscopic submucosal dissection in elderly patients with early gastric cancer.

Objectives Endoscopic submucosal dissection (ESD) has advantages over conventional endoscopic mucosa resection. The number of elderly patients (more than 75 years old) with early gastric cancer (EGC) has been steadily increasing. We sought to assess clinical outcomes of ESD for EGC in elderly. Methods ESD was performed for patients with EGC, who fulfilled the criteria for ESD: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings 3 cm or less in diameter; and minute submucosal invasive cancer 3 cm or less in size. Two hundred and sixty elderly patients (≥75 years old) with 279 lesions, and 401 non-elderly patients with 434 lesions were enrolled to this study. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6–89 months (median: 30 months). Resectability (en-bloc or piecemeal resection), curability (curative or noncurative resection), completeness (complete or incomplete resection), complications, and survival rates were assessed. Rersults The one-piece resection rate was significantly lower in elderly patients (93.9%) than in non-elderly patients (97.9%). The complete resection rate was significantly lower in elderly patients (87.4%) than in non-elderly patients (96.6%). Pneumonia, but not bleeding or perforation, developed in association with ESD more frequently in the elderly patients by 2.2%. Local tumor recurrence was quite rare, and the overall and disease-free survival rates were acceptable irrespective of age. Conclusion En-bloc and complete resections were achieved less frequently in elderly patients, but the long-term outcomes in elderly EGC patients may be excellent, and ESD is a feasible treatment in the elderly.

Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia.

Background and Goals Neurohormonal factors might play a role in the pathogenesis of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal hormone that stimulates gastric motility, in FD is not yet clearly defined. The present study was designed to investigate plasma ghrelin levels and their relation with gastric emptying and psychologic status in FD. Methods Sixteen patients with FD of the dysmotility type and 19 healthy controls were enrolled in the study. Plasma active and desacyl ghrelin concentrations before and after test meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and psychologic condition were studied using 13C acetate breath test and questionnaires, respectively. Results Gastric emptying was significantly prolonged in patients with FD compared with controls. Fasting desacyl and total ghrelin levels were significantly lower in FD patients than in controls, but fasting active ghrelin levels and postprandial levels of ghrelin in both forms were similar between the 2 groups. Fasting total ghrelin levels in FD patients did not differ from the postprandial levels, in contrast to what was found for controls. There was no significant association among gastric emptying, plasma ghrelin levels, and psychologic factors in FD patients. Conclusions Total secretory ability or metabolic condition of ghrelin may be altered in patients with FD. This seems to play a role in the pathophysiology of dysmotility type FD, independent of delayed gastric emptying or psychologic disorders.

Endoscopic Submucosal Dissection for Colorectal Epithelial Neoplasms

PURPOSE: Endoscopic submucosal dissection permits removal of colorectal epithelial neoplasms en bloc, but long-term clinical outcomes remain unknown. METHODS: Endoscopic submucosal dissection was performed in 282 patients having 296 colorectal tumors that fulfilled the inclusion criteria, which included lesions greater than 20 mm in size for which en bloc resection would be difficult with endoscopic mucosal resection, lesions with fibrotic scar due to previous endoscopic treatment or biopsies, locally residual lesions after endoscopic resection, or invasive carcinoma with slight submucosal penetration. En bloc or piecemeal resection, complete (en bloc with tumor-free lateral/basal margins) or incomplete resection, and complications were assessed, and factors related to each were analyzed using logistic regression. Patients with early colon cancer received endoscopic follow-up and metastatic surveys for a median of 34 months. RESULTS: En bloc resection was achieved in 89.2% (264/296) and 234 lesions (79.1%) were deemed to have undergone complete resection. A right-side colonic location was the significant contributor to incomplete resection. Perforation was seen in 24 cases (8.1%) in association with tumor size and the presence of fibrosis. There was 1 case of locally recurrent tumor with incomplete resection, whereas neither recurrence nor residual disease was observed in the complete resection group. Neither cancer-related nor cancer-unrelated death was observed. CONCLUSIONS: Precise assessment of curability with successful en bloc resection may reduce tumor recurrence after endoscopic submucosal dissection. The prognosis of early colorectal cancer in patients treated by endoscopic submucosal dissection is likely to be excellent, although further longer follow-up studies are warranted.