Search

We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription-PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh-EMT pathway. Our proposed extensive Hh-EMT signal pathway has the potential to an understanding of diffuse-type GC and to the development of new drugs. [ABSTRACT FROM AUTHOR]

Objectives: Anastomotic leakage (AL) is a serious complication associated with morbidity, mortality, and poor prognosis. This study aimed to identify the risk factors and predictive biomarkers for AL after colorectal surgery with double stapling technique (DST) anastomosis., Methods: We retrospectively analyzed 331 patients who underwent elective colorectal cancer surgery with DST anastomosis between April 2012 and July 2021. Patient-, tumor-, and surgery-related variables were examined using univariate and multivariate analyses to identify the risk factors for AL. Postoperative inflammatory biomarkers were also analyzed to identify the predictive factors for AL., Results: AL occurred in 28 (8.5%) patients. In multivariate analysis, male sex, a history of diabetes mellitus and high ligation of inferior mesenteric artery (IMA) were significant risk factors for AL. Serum C-reactive protein (CRP) levels on postoperative day (POD) 3 and 7 were significantly correlated with AL (OR; 95% CI, 1.134; 1.044-1.232, p = 0.003, and 1.154; 1.036-1.286, p = 0.009, respectively). The cut-off value of CRP on POD 3 was 10.91 mg/dL (sensitivity 0.714, specificity 0.835, positive predictive value [PPV] 0.290, and negative predictive value [NPV] 0.969). The cut-off value of CRP on POD 7 was 4.58 mg/dL (sensitivity 0.821, specificity 0.872, PPV 0.377, and NPV 0.981)., Conclusions: Male sex, a history of diabetes mellitus and high ligation of IMA were risk factors for AL in colorectal cancer surgery with DST anastomosis. The predictive biomarkers for cases without AL were CRP levels on POD 3 and 7., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2023 The Japan Society of Coloproctology.)

We evaluated the efficacy of neoadjuvant chemotherapy(NAC)for 38 patients with locally advanced rectal cancer (LARC). We administered mFOLFOX6 in 15, FOLFIRI in 3, CAPOX in 10, IRIS in 1 and FOLFOXIRI in 9 patients. We also used bevacizumab in 31 and panitumumab in 7 patients. There were 27 male and 11 female patients, with a median age of 64 years, and location was RS 2, Ra 9, Rb 21, and P 6. Synchronous distant metastasis was recognized in 13 patients. Nine patients had suffered adverse event of Grade 3, however all patients could complete NAC. Clinical response was CR 3, PR 31, SD 4, response rate was 91.9%, and reduction rate was 43.3(range 18.8-100)%. Clinical response of distant metastasis was CR 3, PR 9 and SD 1. Laparoscopic surgery was performed in 29 patients. Postoperative complications of Grade 2 of Clavien- Dindo classification were recognized in 14 and Grade 3 in 4 patients. Three- and five-year overall survival rate of 25 patients without distant metastasis were 79.6% and 74.9%, respectively; and 13 with distant metastasis were 61.6% and 52.6%, respectively. The efficacy, safety and postoperative outcomes of NAC for LARC are favorable, and we think that NAC will be one of the treatments for LARC.

A 74-year-old woman presented to her local physician with hematochezia. Colonoscopy showed a locally advanced 30 mm cancer adjacent to the anus. She refused abdominoperineal resection because of the necessity for a permanent stoma and decided to receive proton beam therapy (70.4 Gy equivalent) as an alternative treatment in another hospital. After proton beam therapy, the rectal cancer was eradicated at colonoscopy, and she was referred for surveillance. One year later, she developed frequent hematochezia. Colonoscopy revealed dilated vessels with oozing hemorrhage in the tumor scar. This was diagnosed as hemorrhagic radiation proctitis induced by proton beam therapy. Over 8 months, endoscopic hemostatic therapy was performed five times using argon plasma coagulation for refractory hemorrhagic disease. The patient's hemoglobin level dropped to as low as 4.5 g/dl requiring blood transfusion. Thereafter, the radiation proctitis gradually improved and there is no evidence of recurrent tumor for over 10 years. To the best of our knowledge, there are no previous reports of proton beam therapy eradication of locally advanced rectal cancer. Clinicians should be aware that radiation-induced proctitis with refractory hemorrhage could develop., (© 2022. Japanese Society of Gastroenterology.)

Objectives: Endoscopic submucosal dissection (ESD) of colorectal lesions was invented in Japan, but postoperative management including hospital stay has not been reconsidered due to the Japanese insurance system. To explore appropriate postoperative management after colorectal ESD, we reviewed short-term outcomes after ESD in non-selected consecutive patients., Methods: Patients who underwent colorectal ESD from April 2013 to September 2020 in one institution were reviewed. The primary outcome measure was the occurrence of adverse events stratified by the Clavien-Dindo classification with five grades. A logistic regression model with the Firth procedure was applied to investigate predictors of severe (grade III or greater) adverse events., Results: A total of 330 patients (female 40%, male 60%; median 72 years; IQR 65-80 years) with colorectal lesions (median 30 mm, IQR 23-40 mm; colon 77%, rectum 23%; serrated lesion 4%, adenoma 47%, mucosal cancer 30%, invasive cancer 18%) was evaluated. The en bloc resection rate was 97%. The median dissection time was 58 min (IQR: 38-86). Intraprocedural perforation occurred in 3%, all successfully treated by endoscopic clipping. No delayed perforations occurred. Postprocedural bleeding occurred in 3% on days 1-10 (median day 2); all were controlled endoscopically. Severe adverse events included only delayed bleeding. In analyzing severe adverse events in a multivariate logistic regression model with the Firth procedure, antithrombotic agent use ( p = 0.016) and rectal lesions ( p = 0.0010) were both significant predictors., Conclusions: No serious adverse events occurred in this series. Four days of hospitalization may be too long for the majority of patients after ESD., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Cold snare polypectomy is being increasingly adopted; however, there are few reports of cold snare polypectomy regarding antithrombotic therapy., Aims: This study aimed to investigate the real-world safety of cold snare polypectomy during antithrombotic therapy., Methods: We collected data from consecutive patients undergoing cold snare polypectomy in a single hospital between 2013 and 2017. Indications for cold snare polypectomy were any ≤ 10 mm polyp. The primary outcome was delayed bleeding. We compared rates of delayed bleeding between patients with and without antithrombotic therapy and analyzed risk factors for delayed bleeding using binary logistic regression model with firth procedure., Results: In 2152 patients (mean age 67.6 years; male 1411), 4433 colorectal polyps (mean diameter 5.0 mm) underwent cold snare polypectomy. Clipping during the procedure was performed for 5.8%. Delayed bleeding occurred in 0.51% (11/2152) of patients and 0.25% (11/4433) of polyps, but no major delayed bleeding occurred. A total of 244 (11%) patients received antithrombotic therapy. Patients on antithrombotic therapy were older (p < 0.001), more likely male (p < 0.001) and had cold snare polypectomy in the proximal colon (p = 0.011). The rate of delayed bleeding was higher in patients on antithrombotic therapy (1.64% vs. non-antithrombotic therapy 0.37%, p = 0.009). Larger polyp size (> 5 mm), use of clips, and antithrombotic therapy were significant risk factors for delayed bleeding. There was no clear association between specific antithrombotic agents and delayed bleeding., Conclusions: Delayed bleeding after cold snare polypectomy was rare even in patients with antithrombotic therapy, and no major delayed bleeding occurred., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are many reports on the choice of treatment for and prognosis of left-sided obstructive colorectal cancer; however, few studies have focused on the prognostic factors of left-sided obstructive colorectal cancer. Therefore, we analyzed the prognostic factors using a post hoc analysis of a retrospective multicenter study in Japan., Methods: A total of 301 patients were enrolled in this study to investigate the prognostic factors for relapse-free survival. The relationships between sex, age, decompression for bridge to surgery, depth of invasion, lymph node metastasis, postoperative complications, adjuvant chemotherapy, carcinoembryonic antigen, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, and relapse-free survival were examined., Results: No change in the decompression method, T3 cancer, negative postoperative complications (grades 0-1 of Clavien-Dindo classification), and adjuvant chemotherapy during Stage III indicated a significantly better prognosis in a Cox univariate analysis. Lymph node metastasis was not selected as a prognostic factor. Excluding patients with <12 harvested lymph nodes (possible stage migration), lymph node metastasis was determined as a prognostic factor. In a Cox multivariate analysis, change in the decompression method, depth of invasion, lymph node metastasis (excluding N0 cases with <12 harvested lymph nodes), and adjuvant chemotherapy were prognostic factors., Conclusions: Similar to those in nonobstructive colorectal cancer, depth of invasion and lymph node metastasis were prognostic factors in left-sided obstructive colorectal cancer, and patients with <12 dissected lymph nodes experienced stage migration. Stage migration may result in disadvantages, such as not being able to receive adjuvant chemotherapy., (© 2022. The Author(s).)

Background: Computed tomography colonography (CTC) may be superior to colonoscopy and barium enema for detecting diverticula. However, few studies have used CTC to diagnose diverticula., Aim: To evaluate the current prevalence and distribution of colonic diverticula in Japan using CTC., Methods: This study was conducted as part of the Japanese National Computed Tomographic Colonography Trial, which included 1181 participants from 14 hospitals in Japan. We analyzed the prevalence and distribution of colonic diverticula and their relationships with age and sex. The relationship between the diverticula and the length of the large intestine was also analyzed., Results: Diverticulosis was present in 48.1% of the participants. The prevalence of diverticulosis was higher in the older participants ( P < 0.001 for trend). The diverticula seen in younger participants were predominantly located in the right-sided colon. Older participants had a higher frequency of bilateral type (located in the right- and left-sided colon) diverticulosis ( P < 0.001 for trend). The length of the large intestine with multiple diverticula in the sigmoid colon was significantly shorter in those without diverticula ( P < 0.001)., Conclusion: The prevalence of colonic diverticulosis in Japan is higher than that previously reported. The prevalence was higher, and the distribution tended to be bilateral in older participants., Competing Interests: Conflict-of-interest statement: We have no financial relationship to disclosure., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The neutrophil-to-lymphocyte ratio (NLR) has been reported to be an independent prognostic factor of unresectable advanced or metastatic colorectal cancer (uCRC). However, few studies have documented changes in NLR during chemotherapy. The current study analyzed whether a change in NLR during chemotherapy in patients with uCRC could be used as a prognostic biomarker. The present retrospective study enrolled 71 patients who received first-line chemotherapy for uCRC between April 2012 and April 2019. The exclusion criteria were as follows: Acute infection or systemic inflammatory disease, duration of first-line chemotherapy <3 months, curative resection after chemotherapy and treatment with granulocyte-colony stimulating factor within 1 month. NLR, Lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase, alkaline phosphatase (ALP), albumin, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were calculated before chemotherapy and at 3 months after chemotherapy. Among these laboratory data, NLR, PLR, ALP, CEA and CA19-9 levels were significantly decreased during chemotherapy. For Cox univariate analyses, these five data makers were divided into two groups: Decreased and increased (comparing before and at 3 months after chemotherapy). Only the change in NLR was significantly associated with overall survival (P=0.0002). Furthermore, the overall survival (P<0.0001) and progression-free survival (P=0.0041) of patients with decreased NLR was increased compared with patients with increased NLR. The change in NLR from pre-chemotherapy to 3 months following chemotherapy was determined to be a predictor of prognosis in patients with uCRC. The ability to predict prognosis at an early phase of chemotherapy may provide useful information for the selection of subsequent treatment and may improve the quality of patient life., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Nemoto et al.)

Small intestinal hemorrhage due to diverticulum is a relatively rare condition among gastrointestinal hemorrhages. We report a case of diverticular hemorrhage of the terminal ileum that was successfully treated by ultra-selective transcatheter arterial embolization using a triaxial system. A 25-year-old man was referred to our hospital due to melena. Abdominal contrast-enhanced computed tomography demonstrated marked extravasation of contrast medium in a diverticulum of the terminal ileum. We immediately attempted transcatheter arterial embolization after onset of hemorrhagic hypovolemic shock. Angiogram of the superior mesenteric artery revealed apparent hemorrhage at the end of the ileocolic artery. We performed embolization with 2 platinum coils using a triaxial system via the vasa recta of the terminal ileum. This procedure stopped extravasation of contrast medium. Postoperative course was uneventful, and he was discharged four days postoperatively. The triaxial system may facilitate high diagnostic ability to accurately identify target arteries of the ileal diverticular hemorrhage.

Background and Study Aims: Small polyps are occasionally missed during colonoscopy. This study was conducted to validate the diagnostic performance of a polyp-detection algorithm to alert endoscopists to unrecognized lesions., Methods: A computer-aided detection (CADe) algorithm was developed based on convolutional neural networks using training data from 1991 still colonoscopy images from 283 subjects with adenomatous polyps. The CADe algorithm was evaluated on a validation dataset including 50 short videos with 1-2 polyps (3.5 ± 1.5 mm, range 2-8 mm) and 50 videos without polyps. Two expert colonoscopists and two physicians in training separately read the same videos, blinded to the presence of polyps. The CADe algorithm was also evaluated using eight full videos with polyps and seven full videos without a polyp., Results: The per-video sensitivity of CADe for polyp detection was 88% and the per-frame false-positive rate was 2.8%, with a confidence level of ≥30%. The per-video sensitivity of both experts was 88%, and the sensitivities of the two physicians in training were 84% and 76%. For each reader, the frames with missed polyps appearing on short videos were significantly less than the frames with detected polyps, but no trends were observed regarding polyp size, morphology or color. For full video readings, per-polyp sensitivity was 100% with a per-frame false-positive rate of 1.7%, and per-frame specificity of 98.3%., Conclusions: The sensitivity of CADe to detect small polyps was almost equivalent to experts and superior to physicians in training. A clinical trial using CADe is warranted., (© 2020 Japan Gastroenterological Endoscopy Society.)

We report 2 cases of advanced colorectal cancer achieving complete response by FOLFOXIRI plus bevacizumab. Case 1 was a 65-year-old male diagnosed with descending colon cancer with multiple liver metastases. Six courses of FOLFOXIRI plus bevacizumab were administered after laparoscopic-assisted left hemicolectomy. Ten partial hepatectomies and 1 radiofrequency ablation were performed as the liver metastases resolved. A pathological complete response was confirmed. Adjuvant chemotherapy was not administered, and recurrence-free survival was 21 months after hepatectomy. Case 2 was a 77-yearold male diagnosed with rectal cancer invading the pelvic wall and sacral foramen with bilateral lateral lymph node metastasis. Additionally, there was a cancer embolism in the right internal iliac vein. Six courses of FOLFOXIRI plus bevacizumab were administered, and the cancer tissue was absent on subsequent CT and MRI. The cancer was scarred by colonoscopy, and the biopsy showed no malignant cells. Six courses of FOLFIRI plus panitumumab were administered as second-line chemotherapy, and the patient survived without any recurrence after 12 months from initiation of chemotherapy.

Objectives: The aim of this study is to investigate the feasibility of bowel preparation using a hypertonic laxative (polyethylene glycol with ascorbic acid, PEG + Asc) for CT colonography (CTC) and to examine the volume limit of laxative., Methods: In one institution, patients who met the indications for CTC were enrolled and randomly assigned to CTC with regimen A (800 ml PEG + Asc), B (600 ml PEG + Asc), or C (400 ml PEG + Asc). Sodium diatrizoate was given orally for fecal tagging. On the previous day, patients ate low-residue meals and took the assigned lavage solution after dinner. A reader blinded to the preparation graded residual stool/fluid and fecal tagging quality in six segments of the colorectum. The primary outcome was a proportion of colon segments without stool. One hundred twenty segments in 20 patients with each regimen were needed to show a non-inferiority margin of 15%, assuming 85% of no stool., Results: A total of 360 segments in 60 patients were analyzed. There were 83% of segments with no stool in regimen A, 89% in regimen B, and 88% in regimen C. Using the delta method, the 95% confidence interval of the risk difference (6.7%) between regimens A and B was - 2.2% to 15.6%, and the risk difference (5.0%) between regimens A and C was - 4.1% to 14%, both within the non-inferiority margin. Residual fluid and fecal tagging quality were also within the non-inferiority margin. No adverse events occurred., Conclusions: A novel CTC regimen using hypertonic laxative demonstrated optimal colon cleansing effectiveness even with the lowest volume of laxative (UMIN000022851)., Key Points: • A novel CTC regimen using a hypertonic laxative is feasible. • The lowest volume of laxative provides excellent colon imaging. • However, the lowest volume of laxative did not improve patient acceptance.

Background and study aims  Delayed bleeding is believed to occur less frequently after cold snare polypectomy (CSP), but this has not been validated in clinical trials. This study aimed to compare rates of delayed bleeding after CSP and hot snare polypectomy (HSP). Patients and methods  We conducted a multicenter, randomized controlled trial. Participants scheduled to undergo endoscopic resection of colorectal polyps ≤ 10 mm were enrolled and randomly assigned to CSP or HSP. Prophylactic clipping was performed at the endoscopists' discretion. The primary outcome was delayed bleeding rate. Secondary outcomes included immediate bleeding rate and clipping rate. Sample size calculation showed that 451 patients were required in each arm. Results  At the end of the study period decided in advance, 308 participants were recruited and an interim analysis was performed. A total of 273 patients (mean age 62.2 ± 8.8 years; 188 males) were analyzed, with 139 patients allocated to CSP and 134 to HSP. In total, 367 polyps were resected with CSP and 360 polyps with HSP. There were no significant differences in patient demographics or polyp characteristics. In per-patient-based analysis, delayed bleeding rates were 0.7 % after CSP and 0.7 % after HSP. Per-polyp analysis showed similar results (CSP: 0.3 % vs. HSP: 0.6 %). The immediate bleeding rate was significantly higher with CSP vs. HSP (54 % vs.14 %, P  < 0.0001), while clipping rates were 18 % and 19 %, respectively. Conclusion  This interim analysis did not demonstrate that delayed bleeding after CSP is less frequent than after HSP. The delayed bleeding rate after HSP was lower than expected. Meeting presentations: Digestive Disease Week 2017.

A 53-year-old woman was referred to our hospital with melena. Examinations revealed advanced rectal cancer involving the anal canal with invasion of the left-sided levator ani muscle. Neoadjuvant chemotherapy was administered to preserve anal function. A first course of capecitabine and oxaliplatin(CapeOX)plus bevacizumab was administered. CapeOX plus panitumumab was administered from the 2nd to the 8th courses after confirming the absence of RAS mutation. Endoscopy and computed tomography confirmed the disappearance of the tumor after completion of the chemotherapy. A biopsy of the scar tissue revealed no cancer cells. However, diffusion weighted-magnetic resonance imaging(MRI-DWI)revealed a suspected residual tumor. To determine the subsequent treatment, a transanal resection was performed. No carcinoma was identified in the specimen. Thus, additional surgical treatment and adjuvant chemotherapy were not administered. The patient was followed-up over 2.5 years post local resection and showed no recurrence.

Objectives: Colonoscopy is the first-line modality to examine the colon even in the very elderly but may have an increased risk of complications. This study aimed to evaluate the efficacy and safety of colonoscopy in the very elderly., Methods: Patients ≥85y old, who underwent colonoscopy between September 2010 and August 2012 in two tertiary-care hospitals in Japan were enrolled. Main outcome measures were cecal intubation rate, detection rate of adenomas and cancers, treatment, adverse events, and long-term outcomes., Results: A total of 207 colonoscopies were performed in 177 patients (females 72, males 105; maximum age 95 years). Of these, 202 attempted to reach the cecum, with success in 92%. Excluding patients with known colorectal neoplasms, invasive cancers were detected in 12%, including T1 lesions in 2% and T2 or deeper in 9%. No cancers were detected in patients referred for surveillance or mild abdominal symptoms. Cancers were found in 25% of patients with positive fecal immunochemical tests, 22% with altered bowel habits, 21% with anemia, and 18% with hematochezia. Treatment of 29 patients with cancer included surgery in 22, endoscopic resection in two and no treatment (due to comorbidities) in five. There were no complications. During 730 days (mean) of follow up, 27 patients died but only three died from recurrent colorectal cancer., Conclusions: Colonoscopy for patients aged ≥85 years is safe. A relatively high detection rate of cancers was found, and most were treatable and even curable. (UMIN000018575)., Competing Interests: Conflicts of Interest There are no conflicts of interest.

Background: Delayed postpolypectomy bleeding occurs more frequently after hot resection than after cold resection., Objective: To elucidate the underlying mechanism, we performed a histological comparison of tissue after cold and hot snare resections., Design: This is a prospective study, registered in the University Hospital Medical Information Network (UMIN000020104)., Setting: This study was conducted at Aizu Medical Center, Fukushima Medical University, Japan., Patients: Fifteen patients scheduled to undergo resection of colorectal cancer were enrolled., Intervention: On the day before surgery, 2 mucosal resections (hot and cold) of normal mucosa were performed on each patient using the same snare without saline injection. The difference was only the application of electrocautery or not. Resection sites were placed close to the cancer to be included in the surgical specimen., Main Outcome Measures: The primary outcome measure was the depth of destruction. Secondary outcome measures included the width of destruction, depth of the remaining submucosa, and number of vessels remaining at the resection sites. The number and diameter of vessels in undamaged submucosa were also evaluated., Results: All cold resections were limited to the shallow submucosa, whereas 60% of hot resections advanced to the deep submucosa and 20% to the muscularis propria (p < 0.001). There was no significant difference in the width of destruction. The number of remaining large vessels after hot resections trended toward fewer (p = 0.15) with a decreased depth of remaining submucosa (p = 0.007). In the deep submucosa, the vessel diameter was larger (p < 0.001) and the number of large vessels was greater (p = 0.018)., Limitations: Histological assessment was not blinded to the 2 reviewers. Normal mucosa was used instead of adenomatous tissue., Conclusions: Hot resection caused damage to deeper layers involving more large vessels. This may explain the mechanism for the reduced incidence of hemorrhage after cold snare polypectomy. See Video Abstract at http://links.lww.com/DCR/A631.

Background and Study Aims:  Topical peppermint oil prevents intestinal spasm, but can cause rebound spasm. Lidocaine hydrochloride, a local anesthetic, may work as an antispasmodic by blocking Na + channels. The aim of this study was to investigate the effect of topical lidocaine on the inhibition of colonic spasm during colonoscopy, compared with peppermint oil., Patients and Methods:  A randomized, controlled double-blind trial was conducted in an academic endoscopy unit. Patients requiring endoscopic resection were randomly allocated to colonoscopy with topical administration of lidocaine (n = 30) or peppermint oil (n = 30). Similar vials containing different solutions were randomly numbered. Allocation was made based on the vial number. The solution used and the vial number were not revealed during the study. Two endoscopists performed all procedures using midazolam, without anticholinergic agents. When a pre-selected lesion was identified, the solution in the assigned vial was dispersed and the bowel observed for 5 minutes. The primary endpoint was the duration of spasm inhibition, and a secondary endpoint was the occurrence of rebound spasm stronger than before dispersion., Results:  There were no significant differences in patient demographics. Spasm was inhibited in almost all patients in both groups, with a similar median duration (lidocaine 227 sec vs. peppermint 212.5 sec, P  = 0.508). In contrast, rebound spasm occurred less frequently in the lidocaine group (lidocaine 7 % vs. peppermint 47 %, P  = 0.001). There were no adverse events or symptoms associated with administration of the solutions., Conclusions:  The inhibitory effect of lidocaine is not superior to peppermint oil. However, lidocaine significantly decreases the frequency of rebound spasms.

Background and Aim: Small-caliber endoscopes such as gastroscopes or pediatric colonoscopes are occasionally required to negotiate fixed or angulated colons. However, the use of a new ultrathin instrument (diameter 7.0 mm) narrower than other conventional colonoscopes has not been evaluated. The aim of the present study was to compare the use compare the use of an ultrathin colonoscope (UTC) with a pediatric colonoscope (PDC) for colonoscopy in older female patients., Methods: A prospective, randomized, controlled trial was conducted in a single academic endoscopy unit. A total of 77 female patients aged ≥70 years undergoing unsedated colonoscopy were randomized to colonoscopy with a UTC (n = 39) or PDC (n = 38). Primary outcome measurement was the degree of pain using a numerical rating scale, and secondary outcomes were cecal intubation rate, ileal intubation rate, time to cecum and adenoma detection rate., Results: There was a significant difference in reported pain using the numerical rating scale (median, UTC 1 vs PDC 4, P < 0.0001). Cecal intubation rates were 97.4% in UTC and 92.1% in PDC (P = 0.36), and ileal intubation rates were 82.0% and 89.4% (P = 0.76), respectively. However, median times to cecum were significantly longer using UTC compared with PDC (15.2 min vs 11.1 min, P = 0.022). Adenoma detection rates were 30.7% in UTC and 26.3% in PDC (P = 0.80)., Conclusions: Colonoscopy using UTC was almost equivalent to that of PDC in older female patients, with significantly less pain compared with PDC. UTC may be an alternative to PDC for the difficult colon., (© 2016 Japan Gastroenterological Endoscopy Society.)

A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal.

During the 1990s, laparoscopic resection was established as a treatment for gastrointestinal malignant tumors.　A number of randomized controlled trials comparing laparoscopic-assisted colorectal surgery with conventional open colorectal surgery for colon cancer have been conducted.　These trials have shown short-term benefits, and the vast majority demonstrated no significant difference in long-term outcomes.　Laparoscopic-assisted colorectal surgery is widely performed for the treatment of colon cancer, whereas laparoscopic-assisted colorectal surgery for rectal cancer is less commonly performed.　In recent years, there have been an increasing number of reports of laparoscopic-assisted colorectal surgery for rectal cancer, where improving short-term outcomes was shown, but no definitive effect on long-term survival has been shown to date.　Randomized controlled trials focusing on long-term survival are currently ongoing.

Blue laser imaging is a new system for image-enhanced endoscopy using laser light. Blue laser imaging utilizes two monochromatic lasers (410 and 450 nm) instead of xenon light. A 410 nm laser visualizes vascular microarchitecture, similar to narrow band imaging, and a 450 nm laser provides white light by excitation. According to three recently published reports, the diagnostic ability of polyp characterization using blue laser imaging compares favorably with narrow band imaging. No published data are available to date regarding polyp detection with blue laser imaging. However, blue laser imaging has the possibility to increase the detection of colorectal polyps by depicting brighter and clearer endoscopic images, even at a distant view, compared with first-generation image-enhanced endoscopy. A clinical trial to compare the detection between blue laser imaging and xenon light is warranted.

Background and Study Aims: Sodium phosphate is a key component of bowel preparation regimen for colon capsule endoscopy (CCE), but may cause serious complications. The aim of this study is to evaluate the use of Gastrografin, substituted for sodium phosphate, in CCE bowel preparation., Patients and Methods: In total, 29 patients (median age 64 years; 23 females) underwent CCE, covered by the national health insurance system of Japan. All had a history of laparotomy and/or previously incomplete colonoscopy. On the day before examination, patients ingested 1 L of polyethylene glycol + ascorbic acid with 0.5 L of water in the evening, and again the same laxative on the morning of examination. After capsule ingestion, 50 mL of Gastrografin diluted with 0.9 L of magnesium citrate was administered, and then repeated after 1 hour., Results: The capsule excretion rate was 97 % (28/29). The median colon transit time was 2 hours 45 minutes and rapid transit (< 40 minutes) through the colon occurred in one patient (3.4 %). Bowel cleansing level was adequate in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. Diluted Gastrografin was well tolerated by patients. No adverse events occurred., Conclusion: Gastrografin can be an alternative to sodium phosphate in CCE bowel preparation regimen.

Background and Study Aims: Bleeding after colonoscopic resection of pedunculated polyps cannot be easily predicted. The aims of this study were to evaluate the blood supply in pedunculated polyps and to clarify the optimal position on the polyp stalk for snare placement to prevent post-polypectomy hemorrhage. ], Patients and Methods: In one institution, 11 pedunculated polyps from 11 patients were studied prospectively. All polyps were resected at the base of the stalk using a snare wire with electrocautery. Histologic axial sections from the apex and base of the stalk were examined with hematoxylin eosin and elastica stains. Elastica stains were used to identify blood vessels. The cross-sectional area of the stalk, total vessel area, maximum diameter of artery/arteriole lumen, number of thick (≥ 0.1 mm) vessels, and number of arteries/arterioles were measured in each section with image processing software. Wilcoxon signed-ranks test was used for comparison., Results: The median polyp diameter was 16 mm (range 7 to 24 mm) and median length of the stalk was 11 mm (range 7 to 23 mm). Two invasive cancers (T1) were included. The maximum diameter of the arterial/arteriolar lumen was greater at the base (P = 0.0044), whereas the ratio of the vessel area to the cross-section area was greater at the apex (P = 0.016). The number of thick vessels and arteries/arterioles were equivalent between apex and base., Conclusions: Morphometric study of the blood supply of pedunculated polyps confirmed that the optimal site for the excision of pedunculated polyps is in the middle of the stalk.

Background and Aim: It has been reported that double-balloon colonoscopy (DBC) is useful for patients after failed colonoscopy. In most cases previously reported, expert colonoscopists have carried out DBC. However, DBC may not require significant expertise. The objective of the present study is to assess DBC carried out by an inexperienced colonoscopist in patients referred after previously incomplete colonoscopy., Methods: In a single center between June 2011 and September 2012, we enrolled 28 consecutive patients referred following incomplete conventional colonoscopy. The reported reasons for previous failed colonoscopy were severe pain during the procedure in 15, long redundant colon in 13 and sigmoid fixation in eight. Under instruction by an experienced colonoscopist, all procedures were carried out by a gastroenterology trainee with little colonoscopy experience. A double-balloon instrument with carbon dioxide insufflation was used under fluoroscopic guidance, with i.v. sedation. Cecal intubation rate, time to cecum and patient-reported pain using a visual analog scale (0 to 10) were evaluated., Results: The trainee achieved a cecal intubation in all patients (100%) without primary involvement by the experienced colonoscopist. Time to cecum ranged from 6 min to 66 min (median time to cecum 15 min 55 s). No patients required additional sedation. Visual analogue pain scores ranged from 0/10 to 10/10 (median score 2.5/10). There were no complications., Conclusion: DBC may enable inexperienced colonoscopists to achieve total colonoscopy after previously incomplete conventional colonoscopy.

We herein report three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent. CASE 1: The hilar lung cancer and its mediastinal lymph node metastasis pressed the esophagus extramurally and caused the marked stenosis. CASE 2: A metastatic lymph node along the left laryngeal nerve caused the stenosis of the trachea. A primary esophageal lesion located at the middle thoracic esophagus also caused the marked stenosis. At first, tracheal stent was placed because of dyspnea, and two weeks later, we placed an esophageal stent. Case 3: Esophageal cancer at lower thoracic esophagus after definitive radiation therapy caused the marked stenosis. Because of the stenosis of esophago-gastric junction( EGJ), we used an esophageal stent with a long cover in order to prevent a reflux into the esophagus. This new Niti-STM esophageal stent was easy to place at the stenosis without difficulty using a conventional device. The symptom was improved immediately for each case. We hope this new device will be used widely.

We evaluated the effectiveness of pre-operative chemotherapy with S-1 plus CDDP against advanced gastric cancer with paraaortic lymph node metastasis. 8 patients received pre-operative chemotherapy with S-1 plus CDDP, according to the following regimen: S-1, 80 mg/m(2), was administered for 21 consecutive days followed by a 14-day rest period, and CDDP, 60 mg/m(2), was administered on day 8. The adverse event rate was 50%. However, a grade greater than 3 was not revealed. There were 5 partial responses (PR) and 3 stable diseases (SD). We performed 7 total gastrectomies and one distal gastrectomy, and the surgical curability (cur) resulted in 6 cases of cur B and two cases of cur C. The histological antitumor effect was grade 2 in three cases. The median overall survival rate was 623 days and the one-year survival rate was 75%. Analyzing for overall survival with antitumor effect and operative curability, both groups of PR and cur B prolonged survival. Pre-operative chemotherapy with S-1 plus CDDP, when used against advanced gastric cancer with paraaortic lymph node metastasis, might be an effective treatment.

Low-grade myofibroblastic sarcoma (LGMFS) is a fusiform cell tumor which develops in bone or soft tissues. This type of tumor frequently occurs in the oral cavity and extremities, while it is extremely rarely found in the abdominal cavity. This article reports a case of LGMFS exceeding 20 cm in diameter in the abdominal cavity observed in a 65-year-old male patient. The patient visited our hospital complaining of a heavy feeling of the stomach and abdominal distension. Imaging examinations revealed a giant solid tumor in the abdomen, and surgical treatment was scheduled. During the operation, a tumor about 20 cm in diameter with its anterior aspect covered with the greater omentum was found. The tumor had firm adhesions to the surrounding tissues, and it was excised with concomitant resections of the tail of the pancreas and the spleen. Histopathologically, fusiform cells were arranged in a complicated or storiform pattern, and immunohistochemical staining revealed that the tumor was positive for α-smooth muscle actin, negative for S100β, H-caldesmon and c-KIT, and a diagnosis of LGMFS was made.

Background/aims: It has been reported that there is a high rate of bone mineral density (BMD) loss after gastrectomy for gastric cancer. To clarify the course of postoperative BMD loss, it is necessary to precisely determine the preoperative BMD of gastric cancer patients., Methodology: From October 2005 through September 2008, preoperative BMD was measured in 91 patients (59 males and 32 females, mean age of the patients was 67.3 years) who underwent gastrectomy for gastric cancer. Then, the percentage of the subject's BMD divided by the BMD of young adult mean (YAM) (% of YAM) was obtained for each subject and the incidence of osteoporosis as well as the relationship between % of YAM and the patient's clinico-pathological factors or biochemical parameters was examined., Results: The incidence of osteoporosis was 15.4%. There is a correlation between BMD in preoperative gastric cancer patients and serum albumin levels, and BMD decreases further in the elderly and individuals with a BMI lower than 18.5., Conclusions: From the viewpoint of osteoporosis prevention, this suggests the importance of nutritional management for elderly gastric cancer patients with associated nutritional disorder.

Nephrotic syndrome associated with a malignant tumor may remit following resection of the tumor. This report documents a case of esophageal cancer with concurrent nephrotic syndrome in which a surgical resection of the tumor resulted in a complete remission of nephrotic syndrome. A 78-year-old male patient noticed edema of his lower legs in February 2009 and was diagnosed with nephrotic syndrome. An endoscopic examination revealed an indented lesion with a nearly semiannular low elevation on the posterior wall of the esophagus at 31 to 34 cm from the upper incisors, and a diagnosis of esophageal cancer was made. A two-stage operation was planned. In March 2009, a subtotal resection of the thoracic esophagus through a right thoracic approach and cervical external esophagostomy were performed, and in April 2009, antethoracic route esophagogastrostomy was performed. The urinary protein levels were negative by the 86th day of hospitalization, and the patient progressively improved and was discharged on the 91st hospital day. There has been no recurrence of esophageal cancer or relapse of nephrotic syndrome at 12 months following the operation. In esophageal cancer patients with nephrotic syndrome, surgical treatment should be undertaken because the remission of nephrotic syndrome may be expected following tumor resection. For this purpose, selecting the appropriate operative procedures and careful perioperative management, including nutritional management, are of profound importance.

A 77-year-old male with thoracic esophageal cancer (cT3N3M0, Stage III) received nedaplatin at 80mg/m2 for 1 day and 5-fluorouracil at 800mg/m2 for 5 days as neoadjuvant treatment. On the fifth day of treatment, he lapsed into a coma (Japan Coma Scale 30), and his serum sodium concentration was found to be decreased to 116mEq/L. We concluded hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone) induced by chemotherapy based on the fact that the patient had no finding of dehydration, particular history of related disorders, serum hypoosmolality accompanied by urine hyperosmolality and persistent urinary sodium excretion. We treated him with fluid restriction, sodium supplement and administration of loop diuretic. Then he regained consciousness and appropriate serum sodium level. Thereafter, hyponatremia was corrected without recurrence, and the patient underwent radical esophagectomy safely. He has been in good condition without recurrence of esophageal cancer after surgery.

It is difficult to perform radical surgery for esophageal cancer with multiple lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is necessary to achieve successful radical resection. The use of neoadjuvant chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an advanced case is reported. The patient (a 67-year-old female) was diagnosed with esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF chemotherapy was initiated in August 2006. Adverse events were mild. A complete response of the lymph node metastases in the abdominal cavity and a partial response of the esophageal lesion were achieved. The surgical procedure included a right thoracolaparotomy followed by a subtotal excision of the esophagus and two-field lymph node dissection. The cancer was diagnosed to be moderately differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The histological efficacy of the chemotherapy was determined to be grade 1a. Two additional courses of DCF therapy were administered followed by postoperative adjuvant chemotherapy.

Purpose: The present study was performed to investigate the effects of the nutrition screening index and pulmonary function test data for patients who underwent surgery for esophageal cancer, based on the incidence of postoperative complications and the duration of postoperative hospitalization., Subjects and Methods: A total of 69 patients who received esophageal cancer resection were included in the study. It was determined how the parameters studied (ie, between ages, concomitant diabetes mellitus, body mass index( BMI), serum albumin level, Onodera's prognostic nutritional index, percentage of vital capacity(%VC), and forced expiratory volume[ FEV]1.0%) were related to the incidence of complications and the duration of postoperative hospital days, as expressed by the median days for all patients and the frequency of long-term hospitalization., Results: The incidence of postoperative complications was significantly higher in patients aged 65 and above and those with a %VC value of less than 80%. The median duration of postoperative hospitalization was longer in those aged 65 and above and those with a FEV1.0% value of less than 70%, which was related to BMI. In addition, the frequency of long-term hospitalization was higher in those aged 65 and above, which was also related to BMI., Conclusions: The results of the present study confirm that postoperative complications and length of postoperative hospital stay in patients with surgically treated esophageal cancer were largely dependent on their pulmonary function as well as age and BMI used for the nutrition screening index. Nutrition screening combined with pulmonary function tests, using age, BMI, %VC, and FEV1.0%, is considered desirable to avoid postoperative complications associated with esophageal cancer.

Background: We developed a modified method of endoscopic aspiration mucosectomy (m-EAM) which includes the pre-cutting of the peripheral mucosa before aspiration, and which has been employed in this department since 1998. An endoscopic submucosal dissection (ESD), which enables the resection of a larger area of the lesion using newly-developed surgical devices, has also been employed here since March 2003. This study was performed to investigate the efficacy of ESD at the present time by assessing the short-term therapeutic results for the procedure in patients with a preoperative diagnosis of early-stage differentiated gastric mucosal cancer, by tumor diameter, as well as by comparing these results with those obtained previously with m-EAM., Patients and Methods: The study included 110 patients with a preoperative diagnosis of early-stage differentiated gastric mucosal cancer (57 underwent m-EAM and 53 received ESD). A comparison was made between these two groups regarding the short-term therapeutic response (en bloc resection rate, curability, complications, and days of postoperative hospitalization) by the tumor diameter., Results: The en bloc resection rate was significantly higher for patients with a tumor measuring 21 mm or larger who underwent ESD in comparison to that for those with a similar tumor size who underwent m-EAM (p<0.05). Complications were reported significantly more frequently in patients treated with ESD for a tumor measuring 11 mm or larger (p<0.05) in comparison those treated with m-EAM. There was no significant difference between the two groups with regard to the curability and the days of postoperative hospitalization., Conclusion: This study confirmed the efficacy of the ESD procedure which enables surgeons to perform a more reliable en bloc tumor resection.

It has been established that the Hedgehog (Hh) and epithelial-mesenchymal transition (EMT) signals act on morphogenesis of embryonic and adult tissues. Recently, both signals have been involved in tumor malignancy. However, little is known as to whether Hh and EMT signals act on normal and malignant epithelial cells in the esophagus. By laser microdissection (LMD)-based microarray and reverse transcription polymerase chain reaction in the undifferentiated and differentiated epithelial cells of the esophagus, we compared the expression profiles of Hh and EMT signaling molecules of these cells with those of cancers. Whether and how both signalings act in undifferentiated cells and in cancer cells are investigated by treatment of a Hh-signal inhibitor and/or siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human esophageal squamous cell carcinoma (ESCC) cell lines. Undifferentiated esophageal epithelial cells and most ESCCs coexpressed Hh and EMT signaling genes. Some mesenchymal-related genes were regulated by an EMT regulator SIP1/ZEB2/ZFHX1B, which was a downstream gene of a primary transcriptional transducer GLI1 in Hh signaling. Hh signal block inhibited esophageal keratinocyte differentiation and cancer cell invasion and growth. These findings suggest that the mesenchymal gene expression of undifferentiated cells is maintained or strengthened in cancer cells through Hh signaling. This is a first report showing the presence of crosstalk between Hh and EMT pathways., (2009 UICC.)

Background/aims: Endoscopic injection sclerotherapy (EIS) has been extensively applied world wide. There are few reports, however, addressing the long-term prognosis (>20 years), although more than two decades have elapsed since the introduction of EIS for esophageal varices. Therefore, the cases of EIS performed in the past 25 years were reviewed to evaluate the long-term results of this procedure., Methodology: There were 602 patients who underwent EIS for esophageal varices between 1981 and 2005, involving a total of 1,964 applications of this procedure. The procedure begins by intravascular injection of 10-20 mL of 5% ethanolamine oleate. The long-term follow-up data were evaluated with primary reference to changes in esophageal varices, survival rate, bleeding rate, causes of death and re-bleeding., Results: In 188 patients with known final endoscopic findings, the gross morphologic status was F1 in 65 patients (34.6%) and F0 in 123 patients (65.4%), only 22 patients (11.7%) were positive for red color sign. The survival rate was 47.4% at 5 years, 25.9% at 10 years, and 13.9% at 15 years. Rebleeding occurred in 93 patients (15.4%). The bleeding rate was 22.9% at 5 years, 28.9% at 10 years, and 28.9% at 15 years. The causes of death were hepatic failure in 244 patients and hepatic cancer in 88 patients, 19 patients died as a result of bleeding from varices (4.8%), 3 patients who died due to therapeutic procedure of EIS., Conclusions: Both the survival rate and rebleeding rate associated with EIS were comparable to those undergoing surgical treatment in patients whose clinical characteristics were matched. EIS is a minimally invasive treatment method that is considered to be an effective first-line treatment for esophageal varices.

We herein report a case of successful treatment with OK-432 administration into lymphatic cyst formed after resection of rectal cancer. A 61-year-old male patient underwent a very low anterior resection with D3 lymphadenectomy for locally advanced rectal cancer. Four months after the surgery, he arrived at our department with lower abdominal fullness. He was diagnosed as having bilateral intra-pelvic abscess by CT scan, and underwent a tube-drainage. After drainage, abscess lesions were shrunk, but a serous discharge remained. Because we diagnosed lymphatic cysts caused by the delayed lymphatic discharge after lymphadenectomy, an administration of OK-432 into cysts was performed. After administration, the discharge was decreased, and then fistula was closed.

Background: We evaluated the role of the prognostic nutritional index reported by Onodera (Onodera's PNI) in patients with gastrointestinal cancer regarding the occurrence of postoperative complications., Method: Subjects were 324 patients (42 with esophageal cancer, 107 with gastric cancer, and 175 with colon cancer). We classified them into the high risk group (< or = 40) and the non-high risk group (> 40) according to Onodera's PNI. We evaluated the rate of the occurrence of postoperative complications between the high risk group and the non-high risk group., Result: The rate of postoperative complications occurring in the high risk group was higher than that of the non-high risk group (p=0.04)., Conclusion: Onodera's PNI is useful for patients with gastrointestinal cancer regarding the occurrence of postoperative complications.

This study was performed to assess the usefulness and safety of neoadjuvant chemotherapy utilizing the FAP regimen consisting of 5-fluorouracil, cisplatin and adriamycin for the treatment of highly advanced esophageal cancer. Twenty-seven patients with Stage III or more advanced esophageal cancer were enrolled in the study. The patients generally received two cycles of FAP. The response rate was as high as 55.6% and the resectability rate as high as 85.2%. All adverse events reported were mild in intensity. The histological effect was assessed as follows: Grade 1 in 18 patients, Grade 2 in 3 patients and Grade 3 (a pathological complete response) in 2 patients. All patients with nonresectable tumors died within 6 months, whereas of the 5 patients who responded with Grade 2 or better histological effects, all survived without recurrence for a follow-up period up to 60 months. The results of this study therefore showed the usefulness and safety of FAP therapy, which is considered to be a treatment method worth aggressively trying for highly advanced esophageal cancer in which a curative resection can hardly be expected.

A 70-year-old male was admitted to our hospital because of advanced esophageal squamous cell carcinoma and early gastric adenocarcinoma. A esophagectomy and partial gastrectomy with three-field lymph node dissection (neck, mediastinum and abdomen) was performed. Both tumors had lymph node metastases. In addition, three mediastinal lymph nodes (two subcarinal lymph nodes and a middle thoracic paraesophageal lymph node) were involved with adenocarcinoma. To elucidate whether they were metastases from the gastric cancer, an immunohistochemical analysis was performed. The cancer cells in these lymph nodes were positive for cytokeratin (CK) 7 and negative for CK 20, thus suggesting metastasis from a nondigestive organ. Interestingly, they were positive for thyroid transcription factor 1 (TTF-1), indicating metastasis from a lung cancer. Since the preoperative computed tomographic scan showed no evidence of lung cancer, a diagnosis of metastases from an occult lung cancer was finally recorded. Ten months after surgery, the patient was alive without a recurrence or the appearance of a lung cancer.

A case of intractable cutaneous fistula in an esophagogastrostomized region complicated by osteomyelitis is reported. A three-stage operation was performed, and gratifying results were obtained. The patient was a 74-year-old man who received a subtotal esophagectomy and a cervical esophagogastrostomy through a retrosternal approach for advanced esophageal cancer. Following subsequent radiotherapy, the anastomosed region in the neck was found to have been stenosed. Endoscopic balloon dilatation was then performed and perforation of the stenosed region occurred to form an intractable fistula. A chest computed tomography scan revealed osteolysis of the sternum, clavicular head and left first rib. Treatment comprised an initial control of the infective foci including osteomyelitis and, after achieving stabilization of the wounds, the subsequent step of reconstruction. The patient's postoperative course was satisfactory without involvement of any leakage or stenosis of the anastomosed regions, or wound infection. It is considered feasible to cure even a cutaneous fistula in the neck complicated by osteomyelitis, as in the present case, by sufficient control of infection and procedural contrivance.

Background/aims: Transradial vascular intervention for heart disease has been expanding recently because it is less invasive, but this approach has only been used to treat abdominal disease at a few institutions. Since 2000, we have performed partial splenic embolization (PSE) via the transradial approach with the aim of achieving the least invasive procedure possible., Methodology: During the past five years, transradial abdominal angiography was performed in 426 patients and eight of them (two men and six women undergoing PSE for LC) were included in this study. They ranged from 48 years to 72 years in age, consisting of three patients in Child class A and five in Child class B. To perform transradial partial splenic embolization, a 4-Fr sheath was inserted in the left radial artery. Under fluoroscopy, intrasplenic branches of the splenic artery supplying about 60-70% of the parenchyma of the spleen were selected and embolized with a newly developed transradial catheter inserted along a guide wire running through the descending aorta. After treatment, the puncture site was compressed by applying a tourniquet. No restriction on movement of the lower or upper extremities is required and the patient is allowed to walk freely., Results: Transradial embolization was successful in all 8 patients. The procedure required 70 minutes on average. The mean platelet count was 3.3x10(4)/microL before treatment, and it increased to 16.3x10(4) and 11.3x10(4)/microL after two weeks and three months, respectively. All patients suffered from fever and pain after treatment, which were treated conservatively. Occlusion of the radial artery, digital paralysis, or splenic abscess did not occur in any patient., Conclusions: This transcatheter technique facilitates hemostasis and requires neither shaving of hair nor insertion of a urinary catheter. In addition, no restriction on movement is needed after the procedure. Consequently, this minimally invasive transradial approach is highly satisfactory for patients and should become a first-line approach for PSE.

Surgical treatment of esophageal cancer is substantially invasive and often entails some postoperative complications. Perioperative management for patients with liver cirrhosis involves great difficulties. Recently, we conducted an esophagectomy for the treatment of superficial esophageal cancer in a 52-year-old male patient with liver cirrhosis and esophageal varices, with gratifying results. Although the hepatic function was impaired, as indicated by a reduced indocyanine green R15 value of 27.4%, the patient was assessed as capable of tolerating operative procedures. The procedures comprised a subtotal esophagectomy through a transhiatal approach, an anastomosis of the cervical esophagus with a gastric tube via the posterior mediastinal route, and super drainage of the short gastric vein of the gastric tube. The patient had an uneventful postoperative course without any complications such as anastomotic leakage or pneumonia. It is considered practicable to accomplish an esophagectomy by careful appraisal of liver function and planning of the operative procedure and perioperative management even in patients with liver cirrhosis.

A case of collision carcinoma (squamous cell carcinoma and Barrett's adenocarcinoma) in the residual cervical esophagus of a 68-year-old woman at 27 years after subtotal esophagectomy for thoracic esophageal carcinoma is reported. The patient initially noticed cervical dysphagia in 2002, but did not seek treatment. In April 2004, the patient was referred to our department by a local physician with the diagnosis of carcinoma of the cervical esophagus. In September 2004, the patient underwent resection of the cervical esophagus and partial resection of the gastric tube combined with cervical lymph node dissection under a diagnosis of double cancer (i.e., metachronous cervical esophageal carcinoma and carcinoma of the gastric tube). Esophagogastric continuity was restored by transplantation of a free jejunal graft with vascular anastomosis. Pathological examination showed squamous cell carcinoma on the esophageal side of the esophagogastric anastomosis and columnar epithelium with a tongue-shaped extension across the anastomotic line that included Barrett's epithelium, as well as adenocarcinoma, on the gastric tube side. The squamous cell carcinoma and adenocarcinoma were contiguous, but there was a distinct border between them and no morphological transition. Immunohistochemical staining showed positivity for p53 in the squamous carcinoma cells, while it was negative in the adenocarcinoma cells. In contrast, HER2 (c-erb-2) was strongly positive in the adenocarcinoma cells, but negative in the squamous carcinoma. Based on these findings, it was concluded that two separate carcinomas had arisen at different sites and grown independently until they collided and merged to form a collision carcinoma.

Studies on molecular mechanisms of self-renewal in normal stem cells are required for understanding the cancer stem cell. Self-renewal in many kinds of normal stem cells might be accelerated in the growth of a young organism and in the repair of damaged tissue. This study examined whether the esophagus in growing neonates provides an experimental system for studies on epithelial stem cell renewal. The esophageal epithelium consists of 3 layers, from the luminal side to the bottom: the differentiated, epibasal and basal cell layers. The basal cell layer is known to contain the stem cells for the esophageal epithelium. This basic architecture is observed both in mice and humans. We investigated the basal cells in the mouse neonate by immunostaining with a basal cell marker, nerve growth factor receptor (Ngfr), and compared the basal cell content in the esophageal epithelium between mice and humans. A mouse esophageal epithelial cell primary culture system was developed for studies on the basal cell growth and keratinocyte differentiation, and microarray analysis was conducted for obtaining expression profiles of the basal cells. It was revealed that the growth of the esophageal epithelium begins from postnatal day 3, and that the timing is consistent with membrane localization of Ngfr in the basal cell. An increase in the basal cell number by Ngf treatment is observed in in vitro mouse esophageal epithelium cultures. Furthermore, mRNA overexpression of Pdgfrb encoding platelet derived growth factor receptor beta and Egfr encoding epidermal growth factor receptor is associated with the timing of the growth of the esophageal epithelium in the neonatal mice. This study provides a new experimental model for studies on the growth of the basal cells, which are considered to include the stem cells, and on the enlargement of the body size in young organisms.

Background & Aims: Sonic hedgehog (SHH) and Indian hedgehog (IHH) have cell-specific actions in some organs. Only SHH has been shown to regulate parietal cell differentiation. This study examined whether SHH, 2 other ligands IHH and Desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers. The effects of a Hedgehog (Hh) inhibitor, cyclopamine, were assessed in primary gastric epithelium cultures and gastric cancer cell lines., Methods: Reverse-transcription polymerase chain reaction and immunostaining compared expression and localization of Hh signaling molecules and phenotypic markers of pit, neck, and gland cells in situ and in cultured cells treated with cyclopamine. Bromodeoxyuridine staining assessed the effects of cyclopamine on proliferation., Results: Hh signaling molecules were expressed differentially in pit, neck, and gland cells. IHH co-expressed with most downstream targets in the pit. IHH, SHH, Patched (PTCH), Smoothened (SMO), and downstream targets were expressed more frequently and highly in the diffuse as compared with intestinal type cancers. In diffuse cancers, IHH was expressed in cells with an epithelial phenotype and SHH in cells with a mesenchymal phenotype. Cyclopamine reduced the number of cells with a pit phenotype but not a gland phenotype in primary cultures. Cyclopamine had particularly potent effects of inhibiting the growth of cell lines that expressed high levels of SMO., Conclusions: Expression of IHH and downstream targets correlates with pit cells. IHH and SMO may be useful biomarkers of diffuse cancers that may show growth inhibition with Hh antagonists such as cyclopamine.