Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing upper gastrointestinal endoscopy: Phase III investigator-initiated clinical trial.

OBJECTIVES: To assess the effectiveness of remimazolam against normal saline (placebo) as a sedative agent for endoscopy in a multicenter, randomized, double-blind, investigator-initiated phase III controlled trial. METHODS: We included 48 Japanese patients undergoing upper gastrointestinal endoscopy. For the procedure, an initial remimazolam dose of 3 mg and additional doses of 1 mg were administered, as determined in the phase II clinical study. The primary study end-point was the successful sedation rate during gastrointestinal endoscopy, determined as a Modified Observer's Assessment of Alertness/Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per 6 min. RESULTS: The successful endoscopy sedation rates were 91.9% and 9.1% in the remimazolam and placebo groups, respectively (P < 0.01). The time from the end of endoscopy to arousal was 0.0 (0.0-0.0) min for both groups. The number of additional doses required to achieve sedation was lower in the remimazolam group than that in the placebo group (P < 0.01). CONCLUSIONS: Remimazolam demonstrated a significantly higher sedation effect during upper gastrointestinal endoscopy in Japanese patients with safe and fast recovery compared with placebo.

Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From Japan.

BACKGROUND & AIMS: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. METHODS: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. RESULTS: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. CONCLUSIONS: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000010136.

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study.

BACKGROUND: Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. METHOD: A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. RESULTS: 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %). CONCLUSION: IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.

Short-term and long-term outcomes of submucosal dissection for residual or recurrent colorectal tumors after endoscopic resection: Analysis of a multicenter prospective study.

OBJECTIVES: We previously demonstrated that a favorable long-term prognosis indicated that endoscopic submucosal dissection (ESD) could be the standard treatment for large colorectal epithelial neoplasms, but the usefulness of ESD for local residual or recurrent tumors with submucosal fibrosis has not been fully demonstrated. The aim of the present study was to assess the usefulness of ESD for local residual or recurrent colorectal tumors. METHODS: We conducted a nationwide multicenter prospective study to evaluate the outcomes of ESD for colorectal tumors. In this post hoc analysis, a total of 54 local residual or recurrent colorectal tumors in 54 patients were included, and we analyzed the short-term and long-term outcomes of ESD for these lesions. RESULTS: The median size of the lesions was 16.0 (interquartile range [IQR] 11-25) mm. ESD was completed in 53 cases (98.1%) with a median procedure time of 65.0 min, but it was discontinued in one case because of submucosal cancer invasion. En bloc resection was achieved in 52 cases (96.3%), whereas R0 resection was achieved in 45 cases (83.3%). Intraoperative perforation was observed in four cases (7.4%) and delayed perforation in one (1.9%), but all cases could be managed conservatively. Delayed bleeding was not observed. There were no significant differences in short-term outcomes between the rectal and colonic lesions. There was no recurrence of the tumor during the median follow-up period of 60 (IQR 50-64) months. CONCLUSION: An analysis of our multicenter prospective study suggests that ESD is an effective salvage management for local residual or recurrent colorectal lesions.

Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.

Outcomes of endoscopic submucosal dissection for colorectal neoplasms: Prospective, multicenter, cohort trial.

OBJECTIVES: Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation. METHODS: A multicenter, large-scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015. RESULTS: ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra- and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%). CONCLUSIONS: This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first-line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136).

Detectability of colorectal neoplastic lesions using a novel endoscopic system with blue laser imaging: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Most studies have not reported an improvement in the detection of adenomas with the use of image-enhanced colonoscopy methods, possibly because of the darkness of the images. To overcome this limitation, a new-generation endoscopic system has been developed. This system has 2 blue-laser imaging (BLI) observation modes. The BLI observation was set to BLI-bright mode to detect lesions. We aimed to evaluate the efficacy of BLI in detecting lesions. METHODS: This study was designed as a randomized controlled trial with participants from 8 institutions. We enrolled patients aged ≥40 years. The participants were randomly assigned to 2 groups: observation by using white-light imaging (WLI) with a conventional xenon light source (WLI group) or observation by using BLI-bright mode with a laser light source (BLI group). All of the detected lesions were resected or had a biopsy taken for histopathologic analysis. The primary outcome was the mean number of adenomas per patient (MAP) that were detected per procedure. RESULTS: The WLI and BLI groups consisted of 474 and 489 patients, respectively. The MAP was significantly higher in the BLI group than in the WLI group (mean ± standard deviation [SD] WLI 1.01 ± 1.36, BLI 1.27 ± 1.73; P = .008). Adenoma detection rate in the BLI group was not significantly higher than in the WLI group. Observation times differed significantly, with BLI (9.48 minutes) being longer than WLI (8.42; P < .001). The mean (± SD) number of polyps per patient was significantly higher in the BLI group compared with the WLI group (WLI 1.43 ± 1.64, BLI 1.84 ± 2.09; P = .001). CONCLUSIONS: A newly developed system that uses BLI improves the detection of adenomatous lesions compared with WLI. (Clinical trial registration number: UMIN 000014555.).

Schwannoma of the stomach with elevated preoperative serum carbohydrate antigen 19-9: report of a case.

We herein report a case of a gastric schwannoma with elevated preoperative serum carbohydrate antigen 19-9 (CA19-9) (155.2 U/ml, normal range 0-36.9 U/ml). A 59-year-old Japanese man was admitted to our hospital for treatment of a submucosal tumor of the stomach detected by barium meal, upper gastrointestinal endoscopy, and computed tomography. Endoscopic examination revealed a 3-cm diameter submucosal tumor in the antrum of the stomach, but biopsy of the lesion was unable to confirm the diagnosis. Positron emission tomography to evaluate the malignant potential showed a high uptake of (18)F-fluorodeoxyglucose in the tumor. Laparoscopy-assisted distal gastrectomy was therefore performed. The histopathological findings of the surgical specimen revealed a benign gastric schwannoma, positive for S-100 protein. The postoperative serum CA19-9 levels gradually decreased and normalized. To the best of our knowledge, this is the first report of a gastric schwannoma with elevated serum CA19-9.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Comparing endoscopic submucosal dissection with transanal resection for non-invasive rectal tumor: a retrospective study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is an alternative to transanal resection (TAR) in treating rectal adenomas, intramucosal cancers, and superficial submucosal cancers. The purpose of this study is to compare the clinical efficacy between ESD and TAR for non-invasive rectal tumors. METHODS: Between January 1998 and December 2006, 85 patients with preoperative diagnosis of non-invasive rectal tumors were treated by ESD or TAR. En-bloc resection, local recurrence, complication, procedure time, and hospital stay were evaluated retrospectively using a prospectively-completed database. RESULTS: Mean resection sizes were 40 mm and 39 mm in diameter for the ESD and TAR groups, respectively. En-bloc resections with a negative resection margin were achieved in 67% (35/52) of the ESD group, which was significantly higher than the 42% (14/33) in the TAR group. Sixty-three lesions were diagnosed as curative resection, histopathologically. There was no local recurrence in the ESD group, but five local recurrences developed in the TAR group. Two rectal perforations, one minor delayed bleeding, and one subcutaneous emphysema in the ESD group were successfully managed conservatively. There were one minor delayed bleeding and two anesthesia-related complications in the TAR group. The ESD group had a shorter hospital stay than the TAR group (4.9 days vs 7 days), but a longer procedure time (131 min vs 63 min). CONCLUSION: ESD was more effective than TAR in treating non-invasive rectal tumors, with a lower recurrence rate and shorter hospital stay.

Pilot study to assess the safety of local lidocaine injections during endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed by endoscopists on patients under sedation. There is an increased risk of anesthesia-related complications due to the higher sedative doses required during lengthier ESDs, so we sought to determine whether a local pain control method could safely reduce such doses. METHODS: Twenty EGC patients enrolled in this study received local lidocaine injections during ESDs at our hospital (lidocaine group; LG). Electrocardiography, heart rate, oxygen saturation, and blood pressure were monitored during and after the ESDs, along with the doses of midazolam and pentazocine. Pain assessments were recorded for LG patients on the day of their ESDs and the following day. RESULTS: The mean volume of lidocaine injection solution was 55.4 ml and the mean dose of lidocaine was 236 mg (range, 100-300 mg). The mean size of the resected specimens was 39.3 mm and mean procedure time was 66.0 min. There were no lidocaine-related complications, and electrocardiography, heart rate, oxygen saturation and blood pressure measurements were normal. In comparison to 157 consecutive patients (control group; CG), who had similar characteristics and had undergone ESDs previously with submucosal injections of conventional normal saline solution, the mean +/- SD pentazocine dose of 15.8 +/- 10.3 mg in the LG was significantly lower (P < 0.01) than the dose of 23.1 +/- 9.5 mg in the CG, and none of the LG patients complained of abdominal pain on the day of their ESDs, whereas such pain was reported by 17% (27/157) of the CG. CONCLUSION: Local lidocaine injections into the submucosal layer were safe when administered during ESDs performed on EGC patients under sedation.

Endoscopic submucosal dissection (ESD) for colorectal tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, however, it is not widely used in the colorectum because of its technical difficulty. OBJECTIVE: To determine the feasibility of using ESD for treating large superficial colorectal tumors. PATIENTS: A total of 400 consecutive patients were treated by ESD for 405 lesions at National Cancer Center Hospital, Tokyo, Japan. INTERVENTIONS: Endoscopic submucosal dissection procedures were performed using a bipolar needle knife (B-knife) or an insulation-tip knife (IT knife). RESULTS: The en-bloc resection rate was 87% and the curative resection rate was 86% among the 405 ESDs: 101 involved tubular adenomas, 255 intramucosal cancers and minute submucosal cancers, 46 submucosal deep cancers and 3 others (MALT and carcinoid tumors). The median operation time was 90 minutes and the mean size of resected specimens was 40 mm (range: 15 mm-150 mm). Perforations occurred in 14 (3.5%) cases and postoperative bleeding in four (1%) cases, but only one perforation case needed emergency surgery because endoscopic clipping was ineffective. LIMITATIONS: Conducted at single center. CONCLUSIONS: Endoscopic submucosal dissection is a feasible technique for treating large superficial colorectal tumors because it provides a higher en-bloc resection rate and is less invasive than surgical resection.

Paget's disease derived in situ from reserve cell hyperplasia, squamous metaplasia, and squamous cell carcinoma of the esophagogastric junction: a case report.

BACKGROUND: Extramammary Paget's disease (EMPD) of the esophagus is a rare tumor, with most cases originating from invasive adenocarcinoma of the esophagus. Pure esophageal Paget's disease, in which no underlying invasive carcinoma component is present, is extremely rare. In this report, we describe a case of EMPD of the esophagogastric junction with no evidence of invasive carcinoma. CASE PRESENTATION: An 81-year-old Japanese woman with a 2-week history of abdominal distension presented to our hospital for assessment. Endoscopic examination revealed a mild elevated granular lesion, with a slightly depressed irregular mucosa, in the distal esophagus, with EMPD confirmed by biopsy. Thoracoscopic esophagectomy with lymph node dissection was performed, with Paget cells observed on microscopic examination in the lower part of the esophageal epithelium. Only a few Paget cells stained positively for PAS/Alcian blue. Immunohistochemically, negative staining for CK5 and p63 were identified in the Paget cells, with positive staining for CK7. Furthermore, an intraepithelial squamous cell carcinoma, with squamous metaplasia and reserve cell hyperplasia, was observed in the gastric mucosa of the esophagogastric junction, adjacent to the Paget cells. CONCLUSIONS: EMPD of the esophagus is a rare disease. We report a case of EMPD that was probably derived from a gastric squamous cell carcinoma, with squamous cell metaplasia and reserve cell hyperplasia, in the esophagogastric junction, which, to our knowledge, is the first report of this type of EMPD in the clinical literature.

Poorly cohesive adenocarcinoma of the ampulla of Vater: a case report.

A 47-year-old Japanese male was submitted to pancreaticoduodenectomy for an ampullary cancer. Pathologically, the ampullary cancer was poorly cohesive adenocarcinoma without tubular structure. Moreover, locoregional lymph nodes were swollen with hypervascularity, plasmacytes infiltration, and hemorrhage. Our case seems to be different from usual poorly differentiated adenocarcinoma.

Evaluation of abdominal circumference and salivary amylase activities after unsedated colonoscopy using carbon dioxide and air insufflations.

OBJECTIVE: To assess and compare abdominal distention and stress in unsedated colonoscopy using carbon dioxide (CO2 ) and air insufflations. METHODS: Two hundred and five patients underwent colonoscopic examinations without sedation using either CO2 or air insufflation. Abdominal circumference and salivary amylase (sAMY) activities before and 0 and 15 min after colonoscopy were measured by a nurse who was blinded to the grouping of the patients. RESULTS: In all, 102 and 103 patients were randomly recruited in the CO2 and air insufflation groups, respectively. sAMY activities before and 0 and 15 min after colonoscopy were not significantly different between the two groups. Abdominal circumference measured immediately and 15 min after colonoscopy was significantly smaller in CO2 insufflation group than in the air insufflation group (81.2 cm vs 84.0 cm, and 79.7 cm vs 83.6 cm, respectively; P <0.05). The increasing ratio of abdominal circumference immediately after colonoscopy was not significantly different between the two groups; however, the ratio at 15 min after colonoscopy using CO2 insufflation was significantly lower than that in the air insufflation group (1.007 vs 1.028, P <0.001). CONCLUSION: sAMY activities after unsedated colonoscopy using CO2 insufflation were not improved; however, CO2 insufflation decreases abdominal circumference after colonoscopy compared with air insufflation.

A case of mixed adenoneuroendocrine carcinoma of the stomach with focal intestinal metaplasia and hypergastrinemia.

Among neuroendocrine neoplasms, mixed exocrine and endocrine characteristics with at least 30% of each component are classified into mixed adenoneuroendocrine carcinoma (MANEC), according to the 2010 World Health Organization classification. We experienced a rare case of MANEC of the stomach with focal intestinal metaplasia and hypergastrinemia. A 76-year-old Japanese male was diagnosed as having gastric adenocarcinoma and underwent total gastrectomy. The pathologic diagnosis was MANEC of the stomach accompanied by unusual mucosal atrophy without Helicobacter pylori infection, the characteristics of which were different from both type A and type B atrophic gastritis. The patient has a history of long-term use of a proton pump inhibitor. Additional serum chemistry examination using preoperatively obtained plasma from the patient revealed hypergastrinemia. The mechanism of gastric MANEC carcinogenesis is still unclear, but that might be correlated with unusual intestinal metaplasia and hypergastrinemia in this case.

Propofol sedation during endoscopic treatment for early gastric cancer compared to midazolam.

Endoscopic submucosal dissection (ESD) has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurrence. However, the time course of ESD for large gastric tumors is frequently prolonged because of the tumor size and technical difficulties and typically requires higher doses of sedative and pain-controlling drugs. Sedative or anesthetic drugs such as midazolam or propofol are used during the procedure. Therapeutic endoscopy of early gastric cancers can often be performed with only moderate sedation. Compared with midazolam, propofol has a very fast onset of action, short plasma half-life and time to achieve sedation, faster time to recovery and discharge, and results in higher patient satisfaction. For overall success, maintaining safety and stability not only during the procedure but also subsequently in the recovery room and ward is necessary. In obese patients, it is recommended that the injected dose be based on a calculated standard weight. Cooperation between gastroenterologists, surgeons, and anesthesiologists is imperative for a successful ESD procedure.

Intrahepatic biliary dilatation caused by a small simple hepatic cyst: report of a case.

Biliary obstruction caused by small simple cysts is very rare. We present a case of biliary dilatation caused by a simple cyst with a 4-cm diameter. The patient was a 75-year-old woman referred to our hospital for evaluation of a cystic tumor associated with peripheral biliary duct dilatation in the left segment of the liver. Computed tomography and magnetic resonance imaging showed that the cyst probably communicated with the intrahepatic bile duct. Malignant tumors, including intrahepatic papillary neoplasms of the bile duct, could not be ruled out; therefore, we performed surgery with the patient's consent. Histopathologic examination of the resected liver showed that the cystic lesion was a simple cyst. The finding that even small simple cysts can obstruct the biliary tract is important for the management of cystic lesions of the liver.

Recurrent, spontaneous esophageal ruptures associated with antiphospholipid antibody syndrome: report of a case.

A 52-year-old man was admitted to our hospital with a spontaneous esophageal rupture (Boerhaave syndrome) and was successfully treated. Eight years after the first incident, he was readmitted with a recurrent rupture. Recurrence of Boerhaave syndrome is extremely rare, with only 7 cases reported in the English literature. During treatment, the patient was also diagnosed with antiphospholipid syndrome (APS). Although APS is known to cause a variety of symptoms due to vascular thrombosis, recurrence of Boerhaave syndrome, coincident with APS, has never been reported. The pathogenesis of Boerhaave syndrome has not been clearly determined. This report serves to increase awareness of the risk of APS, which results in an increased risk of spontaneous rupture of the esophagus.

Mucosal esophageal squamous cell carcinoma with intramural gastric metastasis invading liver and pancreas: a case report.

A 59-year-old Japanese man was admitted to our hospital because of a 1-month history of dysphagia. Endoscopic examination revealed a superficial esophageal squamous cell carcinoma and a giant gastric tumor. Computed tomography showed that the gastric tumor was directly invading the liver and pancreas. Because of the risk of the gastric tumor causing obstruction and bleeding, we performed a subtotal esophagectomy, proximal gastrectomy, left lateral segmentectomy of liver, and pancreatosplenectomy with gastric tube reconstruction. Final pathological findings were superficial esophageal carcinoma penetrating the muscularis mucosae with an intramural gastric metastasis directly invading the liver and pancreas. The patient received postoperative adjuvant chemotherapy, yet died 8 months postoperatively of complications of local recurrence. Early-stage esophageal carcinoma with intramural gastric metastasis is very rare. To our knowledge, this is the first case of mucosal esophageal carcinoma with intramural gastric metastasis directly invading other organs.