Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissection.

BACKGROUND AND AIMS: Hemostasis during endoscopic submucosal dissection (ESD) can sometimes be challenging and stressful for the endoscopist. Therefore, we aimed to assess the usefulness of dual red imaging (DRI), a new image enhancement technique that uses 3 wavelengths (540, 600, and 630 nm) to visualize bleeding points and to examine the efficacy of DRI in shortening the time required to achieve hemostasis (hemostasis time) during ESD. METHODS: DRI and white-light imaging (WLI) were used alternately for managing 378 bleeding events in 97 patients undergoing ESD. Hemostasis time for each hemostasis event was measured. Using portable eye-tracking glasses, 4 experienced endoscopists were shown random videos of intraoperative bleeding during ESD (20 cases each on WLI and DRI) and identified the bleeding point in each video. The mean distances of eye movement per unit of time until the bleeding point were identified in each video and compared between the WLI and DRI groups. RESULTS: Average hemostasis time was significantly shorter in the DRI group. The mean distance of eye movement was significantly shorter in the DRI group than in the WLI group for all endoscopists. CONCLUSIONS: DRI can offer useful images to help in clearly detecting bleeding points and in facilitating hemostasis during ESD. It is feasible and may help in successfully performing ESD that is safer and faster than WLI. (Clinical trial registration number: UMIN000018309.).

[Operative Technique for Gastric GIST According to the Tumor Location or Growth Pattern].

Gastric gastrointestinal stromal tumor(GIST)is rarely accompanied by lymph node metastasis. Therefore, partial gastrectomy generally proceeds with good indication for laparoscopic surgery. However, surgical procedures can be complicated by the tumor location or growth type. Furthermore, laparoscopy and endoscopy cooperative surgery(LECS)has recently been developed, with good results. In this study, we aimed at determining the applicability of various types of laparoscopic surgery to gastric GIST based on the tumor location and growth type. Between 2005 and 2020, 52 patients underwent surgery for preoperatively suspected or pathologically confirmed GIST. Tumors were found in the upper, middle, and lower portions of the stomach of 32, 16 and 4 patients, respectively. The types of tumor growth were intraluminal, extraluminal, and mixed for 21, 14, and 17 patients, respectively. The surgical procedures were open and laparoscopic for 26 patients each. After the laparoscopic surgery, the surgical duration, blood loss, and tumor size were significantly lower, while the hospital stay was significantly shorter. For the laparoscopic surgery, we adopted simple wedge resection, transillumination and serosal dissection methods(TSDM), or LECS. Two patients underwent TSDM using single incisional laparoscopic surgery(SILS)for tumors with intraluminal growth in the cardiac region, while 7 underwent LECS. The selection of the method for laparoscopic surgery was based on the tumor location or growth type, resulting in good outcomes.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Which part of a porcine stomach is suitable as an animal training model for gastric endoscopic submucosal dissection?

BACKGROUND AND STUDY AIMS: Training using an animal model is generally recommended before performing endoscopic submucosal dissection (ESD) in humans. This study aimed to clarify the suitability of an isolated porcine stomach as an animal training model for gastric ESD. MATERIALS AND METHODS: Study 1: six experienced endoscopists performed ESDs of six simulated lesions located in six locations in an isolated porcine stomach (1, lower third [L]/ greater curvature [Gre]; 2, L/ anterior wall [Ant]; 3, L/ posterior wall [Post]; 4, upper third [U]/ Gre; 5, U/Ant; 6, U/Post). The procedure times (s/cm(2)) were compared among the different lesion locations. A questionnaire (scored 1 - 5) completed by the endoscopists was used to assess the difference in the difficulty compared to the human stomach of the three steps of the ESD procedure (injection, incision and dissection). Study 2: the thicknesses of the mucosal layers were histologically evaluated among the six locations in three porcine and two human stomachs. RESULTS: Study 1: the procedure speed was significantly slower at L/Gre and U/Gre in the porcine stomachs (P = 0.0004). The questionnaire responses revealed a tendency toward similarity between the lower regions of the human and porcine stomachs at L/Ant, L/Post, U/Ant and U/Post during the dissection step (P = 0.056). In contrast, the injection and incision steps at L/Gre in the porcine stomach were shown to differ in difficultly level (both P = 0.0006). Study 2: the mucosal layers in the porcine stomachs were significantly thicker than those in the human stomachs in the lower areas, especially L/Gre. CONCLUSIONS: The difficulty of ESD and the histological features of the porcine stomachs were coincident with those of the human stomachs at L/Ant, L/Post, U/Ant and U/Post. These parts of the porcine stomach may be suitable as animal training models for gastric ESD.

Association between CT-Diagnosed Pneumonia and Endoscopic Submucosal Dissection of Gastric Neoplasms.

BACKGROUND/AIMS: This prospective cohort study aimed to elucidate the incidence and characteristics of pneumonia associated with endoscopic submucosal dissection (ESD) of gastric neoplasms using CT. METHODS: We included consecutive 188 patients with gastric neoplasms treated with ESD. All patients underwent CT before ESD and the day after ESD. Pneumonia associated with ESD was defined as lung ground glass opacity or consolidation by CT the day after ESD. RESULTS: In 188 patients, 28 patients had diabetes mellitus. Pneumonia was observed by CT in 21 patients (11.2%) after ESD. Of those, 7 patients had diabetes mellitus. By univariate analysis, compared with patients with non-pneumonia complications, risk factors for pneumonia were significantly increased in patients with diabetes mellitus (p = 0.01) and in those who underwent a long procedure time (p = 0.02). By multivariate analysis, pneumonia was significantly increased in patients with diabetes mellitus (OR 4.06, 95% CI 1.35-12.19) and in those who underwent a long procedure time (OR 1.01, 95% CI 1.00-1.02). CONCLUSIONS: The incidence of CT-diagnosed pneumonia associated with ESD was relatively high. Furthermore, it was revealed that diabetes mellitus and a long procedure time were risk factors of CT-diagnosed pneumonia.

Feasibility of non-exposed endoscopic wall-inversion surgery with sentinel node basin dissection as a new surgical method for early gastric cancer: a porcine survival study.

Non-exposed endoscopic wall-inversion surgery (NEWS) has been developed as an endoscopic full-thickness resection technique without translumenal communication to avoid intraabdominal infection or tumor seeding. We aimed to investigate the feasibility and safety of NEWS with sentinel node basin dissection (SNBD), which can minimize the area of lymphadenectomy for early gastric cancer (EGC), in 10 porcine survival models. After placing laparoscopic ports and making markings on both the mucosal and serosal sides of a simulated lesion, indocyanine green fluid was endoscopically injected into the submucosa at 4 quadrants around the lesion. An SN basin including the stained SNs was dissected, and a circumferential sero-muscular incision around the lesion and sero-muscular suturing were performed laparoscopically, with the lesion inverted toward the inside of the stomach. Finally, circumferential mucosal incision and transoral retrieval were made endoscopically. In all cases, the lesion was resected in an en bloc fashion, and all pigs survived without adverse events. After 1 week of observation, pigs were sacrificed for macroscopic investigation. The average procedural duration was 170 min (range 130-253 min). Intraoperative perforation occurred in 1 case, which could be safely treated by laparoscopic suturing. The number of dissected SN basins was 1 in 9 cases and 2 in 1 case. Necropsy revealed no signs of severe complication. This animal survival study demonstrated that NEWS with SNBD was safe and feasible. It may provide patients with possibly node-positive EGC a minimally-sized local resection and minimally-ranged lymphadenectomy without the risk of tumor dissemination.

First case of non-exposed endoscopic wall-inversion surgery with sentinel node basin dissection for early gastric cancer.

INTRODUCTION: Non-exposed endoscopic wall-inversion surgery (NEWS) is a novel technique of endoscopic full-thickness resection without transluminal access mainly designed to treat gastric cancer. Here, we report a successful case of NEWS with sentinel node basin dissection (SNBD) for early gastric cancer (EGC) with the risk of lymph node metastasis. PATIENT AND METHODS: A 55-year-old female patient with a 2-cm, diffuse-type intramucosal EGC with ulceration was referred to our hospital for a less invasive gastrectomy based on sentinel node navigation surgery. After obtaining informed consent, NEWS with SNBD was applied. After placing mucosal markings, indocyanine green solution was injected endoscopically into the submucosa around the lesion to examine sentinel nodes (SNs). The SN basin (the area of the left gastric artery), including three stained SNs(#3), was dissected, and an intraoperative pathological diagnosis confirmed that no metastasis had occurred. Subsequently, NEWS was performed for the primary lesion. Serosal markings were placed laparoscopically, submucosal injection was added endoscopically, and circumferential sero-muscular incision and suturing were performed laparoscopically, with the lesion inverted toward the inside of the stomach. Finally, the circumferential mucosal incision was performed, and the lesion was retrieved perorally. RESULTS: The operation was finished in 270 min without complications. The patient was uneventfully discharged 10 days after the procedure. The final pathological diagnosis was coincident with the pre- and intraoperative assessment. CONCLUSIONS: We demonstrated the feasibility and safety of NEWS with SNBD with a favorable result. This surgical concept is expected to become a promising, minimally invasive, function-preserving surgery to cure cases of EGC that are possibly node-positive.

Novel EUS-guided gastrojejunostomy technique using a new double-balloon enteric tube and lumen-apposing metal stent (with videos).

BACKGROUND: Surgical gastrojejunostomy is associated with relatively high morbidity and mortality rates. However, current experimental EUS-guided gastrojejunostomy information is limited. OBJECTIVE: To evaluate a novel EUS-guided gastrojejunostomy technique using a new enteric balloon and lumen-apposing metal stent. DESIGN: Animal experiment. SETTING: Animal laboratory at a referral center. SUBJECTS AND INTERVENTIONS: In 5 pigs, gastrojejunostomies were created under EUS guidance. Fully covered lumen-apposing stents were placed between the stomach and the jejunum. MAIN OUTCOME MEASUREMENTS: Technical success and adverse events of EUS-guided gastrojejunostomy. RESULTS: All stents, with 1 exception, were successfully deployed without any adverse events. The mean time to stent placement was 44.2 minutes (range 28-64 minutes). All animals showed normal eating behavior without signs of infection for 1 month after the procedure. Endoscopic imaging of the stomach site showed the stent to be patent and stable, without dislodgment, in all of the pigs. Necropsy showed complete adhesion between the stomach and the jejunum wall. LIMITATIONS: Pilot study. CONCLUSIONS: Creation of an EUS-guided gastrojejunostomy by using a novel enteric balloon and metal stent appears to be promising as a minimally invasive treatment.

Metachronous adenoma on ileorectal anastomosis suture line and submucosal deep invasive cancer suspected of rapid growth in rectal remnant following long-term interval after curative surgery for advanced colon cancer.

There is general agreement as to the value of postoperative surveillance and the effectiveness of colonoscopy in the early detection of metachronous colorectal lesions. In the present case, a 56-year-old woman with no family history of colon cancer underwent surveillance colonoscopy in which a metachronous flat adenoma was detected following an interval of 23 years after a colectomy and 20 years subsequent to treatment for uterine cancer. A second metachronous flat lesion histopathologically determined to be a submucosal (sm) deep invasive cancer with lymphovascular involvement was detected 12 months later. This second metachronous lesion was suspected of having developed rapidly in the rectal remnant accounting for its sm deep invasion. The findings of this case suggest colonoscopy surveillance guidelines proposed for individuals at high risk should be evaluated based on cancer history and an analysis of possible mismatch repair gene mutations. In addition, the first metachronous lesion was located directly on the suture line of the anastomosis. Endoscopic submucosal dissection (ESD) was indicated despite severe fibrosis into the sm layer. This case also demonstrates the successful use of improved ESD instruments, sm injection agents and technique refinements in the treatment of a technically difficult lesion with a high risk of complications.

Risk factors for perforation and delayed bleeding associated with endoscopic submucosal dissection for early gastric neoplasms: analysis of 1123 lesions.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a useful procedure for the treatment of early gastric neoplasms; however, this advanced technique has also resulted in an increase in serious complications such as perforation and delayed bleeding. This study aimed to elucidate the risk factors for these complications. METHODS: A total of 1123 lesions diagnosed with early gastric neoplasms and treated by ESD at three institutions were investigated. Retrospectively, patients with or without these complications were compared on the basis of the patient characteristics and treatment results. RESULTS: Perforation occurred in 27 lesions (2.4%) and delayed bleeding in 56 lesions (5.0%). Multivariate analysis indicated that lesions located in the upper area of the stomach (odds ratio [OR]: 4.88, 95% confidence interval [CI]: 2.21-10.75) was associated with a significantly higher risk of perforation, and that age ≥ 80 years (OR: 2.15, 95% CI: 1.18-3.90) and a long procedure time (OR: 1.01, 95% CI: 1.001-1.007) were associated with a significantly higher risk of delayed bleeding after ESD. The en bloc resection rate (74% vs 94%) and curative resection rate (48% vs 85%) of lesions with perforation were significantly lower than those without perforation. The rate of residual disease or recurrence after ESD was significantly higher in lesions with delayed bleeding than that without delayed bleeding (5.4% vs 0.84%). CONCLUSIONS: This study demonstrated risk factors for perforation and delayed bleeding associated with ESD. Furthermore, it was clarified that perforation and delayed bleeding influenced post-procedure results and prognosis after ESD.

Development of invasive colon cancer with microsatellite instability in a patient with hyperplastic polyposis syndrome.

The serrated pathway has recently been proposed as a route for the development of colorectal cancer with microsatellite instability. Hyperplastic polyposis syndrome is a rare syndrome defined by the presence of numerous serrated polyps, with a high risk of developing into colorectal cancer. We present here a case of hyperplastic polyposis syndrome developing into colorectal cancer with microsatellite instability from a serrated polyp. BRAF mutation and the loss of MLH1 protein were observed in the colorectal cancer, but not in the other serrated polyps around the colorectal cancer, suggesting that colorectal cancer with microsatellite instability develops rapidly from a specific serrated polyp with distinct molecular properties.

Erratum: Prospective multicenter study of the efficacy and safety of cold forceps polypectomy for ≤ 6-mm non-ampullary duodenal low-grade adenomas.

[This corrects the article DOI: 10.1055/a-1793-9439.].

Prospective multicenter study of the efficacy and safety of cold forceps polypectomy for ≤ 6-mm non-ampullary duodenal low-grade adenomas.

Background and study aims Because the endoscopic treatment for non-ampullary duodenal adenoma (NADA) has a non-negligible risk of adverse events (AEs), a safe and easy treatment for NADA is desirable. This was a multicenter prospective trial evaluating the efficacy and safety of cold forceps polypectomy (CFP) for diminutive NADAs. Patients and methods This study was prospectively conducted at six general hospitals and one university hospital. The inclusion criteria were histologic and endoscopic diagnosis of low-grade NADA measuring ≤ 6 mm. A second endoscopy was scheduled for 1 month after CFP. After confirmation of the success of CFP, 6-month and 12-month surveillance endoscopies were scheduled. The primary endpoint was the endoscopic and histologic disease disappearance rates at the 12-month endoscopy. Results Thirty-nine lesions from 38 patients were prospectively included. Median tumor size at enrollment was 5 mm (range 3-6 mm). There were four cases of remnant lesions at the second endoscopy, and the lesion disappearance rate of single CFP was 89.7 % (35 /39; 95 % confidence interval (CI), 76.9 %-97.9 %). In three cases, complete removal of the lesion was achieved with a single re-CFP, but one case required four repeat CFPs. The lesion disappearance rate at 12-month endoscopy was 97.4 % (38 /39; 95 %CI, 86.8 %-99.5 %). During the follow-up period, no AEs related to CFP were observed. Conclusions CFP for NADA ≤ 6 mm was safe and effective in this study. This common endoscopic method to remove lesions may be an option for treatment of diminutive NADAs.

Clinicopathological characteristics of colorectal serrated polyposis syndrome (SPS): results of a multicenter study by the SPS Study Group in Japan.

BACKGROUND: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan. METHODS: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria. RESULTS: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II. CONCLUSIONS: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.

Clinical outcomes of ESD for early gastric neoplasms in elderly patients.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard treatment in Japan for early gastric neoplasms. With an increase in elderly population, the number of elderly patients in whom ESD performed has also steadily increased. AIMS AND METHODS: The aim of study was to evaluate the effectiveness of and problems associated with ESD for early gastric neoplasms in elderly patients. Subjects were 514 patients (586 lesions) with early gastric neoplasms performed ESD at two institutions. The patients were classified into an elderly group (age ≥ 75 years) and a nonelderly group (age < 75 years). We compared the characteristics of patients and lesions, treatment results, ESD-related complications and prognosis between the two groups. RESULTS: The elderly group included 200 patients (229 lesions), and the nonelderly group included 314 patients (357 lesions). The incidences of underlying disease, such as hypertension and heart disease, and the rate of antiplatelet agents use were significantly higher in the elderly group. En bloc and curative resection rates were high in both groups. The bleeding rate was significantly higher in the elderly group. Residual disease or recurrence rates were very low in both groups. The death rate due to other diseases was significantly higher in the elderly group. CONCLUSIONS: This study demonstrates the efficacy of ESD in both elderly and nonelderly patients. However, we must be attentive to ESD-related bleeding, death caused by other diseases, and underlying diseases when we perform ESD in elderly patients.

Analysis of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the colorectum.

BACKGROUND AND AIMS: Laterally-spreading tumors (LST) are a newly-recognized category of colorectal neoplasia, and are defined as lesions larger than 10 mm in diameter and extending circumferentially rather than vertically. However, genetic features of this new category of tumors are not fully elucidated. The aim of this study was to evaluate genetic alterations in LST. METHODS: We examined K-ras, BRAF, and phosphoinositide-3-kinase catalytic-α polypeptide (PIK3CA) mutations in 101 LST, including 68 LST-granular type (LST-G) and 33 LST-non-granular type by direct sequencing. As controls, we examined these gene mutations in 66 protruded colon adenomas (10 mm or larger) and 44 advanced colon cancers. RESULTS: K-ras, BRAF, and PIK3CA mutations were observed in 59 (58%), zero (0%), and three (3%) LST, respectively. LST-G morphology in the right-sided colon was significantly correlated with the existence of K-ras mutations, whereas a size of 20 mm or larger was the only predictor of mutations in the left-sided colorectum. The frequency of K-ras mutations in LST was particularly marked in the left-sided colorectum compared to protruded adenomas or advanced cancers (LST vs protruded adenomas, P < 0.001; LST vs advanced cancers, P = 0.002), whereas in the right-sided colon, K-ras mutations were equally frequent. PIK3CA mutations were not familiar in either LST (3%) or advanced cancers (9%). CONCLUSIONS: K-ras mutations were involved in colorectal LST in different manners according to tumor location.

Small early gastric cancer with synchronous bone metastasis: A case report.

Bone metastasis during the early stages of gastric cancer is rare, and synchronous bone metastasis is even less common. The present report outlines a case of a small early gastric cancer, which was detected due to bone metastasis. A 63-year-old man was referred to Fukuyama Medical Center with back pain and anorexia of 2 weeks' evolution. MRI revealed multiple metastatic lesions in the thoracic and spinal bone. Fluorodeoxyglucose positron emission tomography revealed focal uptake in the lesser curvature of the stomach and in the spinal bone, pelvic and thigh bone, but uptake was not detected in the stomach. Esophagogastroduodenoscopy revealed a 10 mm slightly elevated lesion with a central depression in the middle-third of the stomach. Endoscopic ultrasonography confirmed that the tumor was confined to the mucosa. A biopsy specimen acquired from the gastric lesion indicated signet-ring cell carcinoma, and the specimen acquired from the lumbar spine revealed cell aggregation such as that found in signet-ring cell carcinoma. The patient received first-line chemotherapy with S-1 and cisplatin, and second-line chemotherapy with nab-paclitaxel. However, the patient died 120 days after consultation at Fukuyama Medical Center.

Methylation of estrogen receptor 1 in colorectal adenomas is not age-dependent, but is correlated with K-ras mutation.

The promoter region of estrogen receptor 1 (ESR1) has been shown to be methylated in normal colorectal mucosa in an age-dependent manner. However, the methylation of this region in colorectal tumors has not sufficiently been investigated. The methylation status of ESR1 in 105 colorectal adenoma tissues was examined by MethyLight and presented as the percentage of methylated references (PMR). Factors that affect the PMR of ESR1 in adenomas were determined using parameters including patient age, sex, past history of malignancy, family history of colorectal cancer, smoking and drinking habits, clinical characteristics of adenomas (location, size, macroscopic appearance, and histology), and K-ras mutation. Multiple linear regression revealed that the PMR was not correlated with patient age. K-ras mutation was significantly correlated with the higher methylation status of ESR1 in adenoma (t-value = 3.21, P = 0.0018), whereas alcohol exposure was significantly correlated with lower methylation status (t-value = -2.37, P = 0.02). Because methylation of O6-methylguanine DNA methyltransferase (MGMT) has been reported to be correlated with K-ras G-to-A transition, methylation of ESR1 was compared with that of MGMT with regard to K-ras mutation. Contrary to expectations, methylation of MGMT was not significantly correlated with K-ras G-to-A transition, but that of ESR1 was strongly correlated with K-ras G-to-A transition. Thus, the methylation status of ESR1 in adenomas was not correlated with patient age, but was associated with K-ras mutation, suggesting that methylation of ESR1 in tumors functions differently from that in normal colon mucosa.

Dual red imaging: a novel endoscopic imaging technology visualizing thick blood vessels in the gastrointestinal wall.

Background Dual red imaging (DRI), a novel image-enhanced endoscopy (IEE) technology, has the potential to improve the visibility of blood vessels in deeper tissue using 600 nm and 630 nm wavelength lights in the red band. Aim To confirm the feasibility of DRI in visualization of vessels in deeper tissue and identify pathologically the features of blood vessels visualized by DRI. Methods Study 1: visibility of blood vessels was assessed by five observers in 137 pairs of DRI and white light imaging (WLI) images. The scores for the visibility of thick blood vessels were measured for randomized images and compared with the scoring template as a reference. The difference in visibility score between DRI and WLI was compared in each pair of images. Study 2: blood vessels detected only by DRI were examined pathologically using two pig stomachs. Results Study 1: The mean visibility scores of DRI and WLI for each observer were 1.69 - 2.26 and 1.31 - 1.67, respectively. The mean difference in visibility score and 95 % confidence interval for the five observers was 0.59 [0.46 - 0.72], 0.54 [0.40 - 0.68], 0.34 [0.18 - 0.49], 0.51 [0.36 - 0.66], and 0.71 [0.54 - 0.88]. The visibility was statistically significantly better in DRI than in WLI for all observers ( P  < 0.0001). Study 2: three blood vessels were observed only by DRI. All of these blood vessels were located at a depth of 1000 - 1500 µm from the mucosal surface. The diameter of these blood vessels exceeded 80 - 200 µm. Conclusions DRI can feasibly detect thick blood vessels in the deep mucosa or submucosa of the gastrointestinal tract.

Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells.

Patients with sporadic microsatellite instable colorectal cancers, in most of which the function of the hMLH1 mismatch repair gene is impaired, do not gain a survival benefit from 5-fluorouracil (5-FU)-based chemotherapy. However, the effect of hMLH1 on the cytotoxicity induced by 5-FU has not yet been sufficiently confirmed. In this study, we assessed the effect of hMLH1 on cytotoxicity and apoptosis induced by 5-FU using newly developed cell lines. We constructed two cell lines: SW480 (originally hMLH1-proficient), in which the expression of hMLH1 was reduced using a small interfering RNA (siRNA) technique, and HCT116 (originally hMLH1-deficient), in which the expression of hMLH1 can be regulated by doxycycline. Using these cell lines, a clonogenic survival assay, 4',6-diamidino-2-phenylindole (DAPI) staining and an Annexin-V assay were performed. Moreover, the incorporation of 5-FU into DNA was determined using tritium-labeled 5-FU. In both of our two cell lines, hMLH1-deficient cells exhibited approximately 2.4-fold clonal surviving fraction compared to hMLH1-proficient cells for 10 days after the administration of 5-FU. Additionally, hMLH1-deficient cells treated with 5-FU exhibited 34-45% less apoptosis than hMLH1-proficient cells according to the results of DAPI staining and Annexin-V assay. Furthermore, hMLH1-deficient cells treated with 5-FU exhibited an approximately 2-fold greater incorporation of 5-FU into DNA than control cells, suggesting that the recognition of 5-FU-incorporated DNA is impaired in hMLH1-deficient cells, resulting in reduced apoptosis. Our conclusions were that decreased expression of hMLH1 in colon cancer cells reduced the apoptosis induced by 5-FU, suggesting that hMLH1 is a key determinant of 5-FU chemosensitivity.