Repeat bidirectional double-balloon enteroscopy 1 year later may be proper in Peutz-Jeghers patients with difficult-to-reach polyps.

Background and study aims Small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS) are sometimes difficult to reach using double-balloon enteroscopy (DBE). However, they can induce intussusception, especially when ≧15 mm. This study aimed to review the outcomes of patients with such polyps. Patients and methods All patients with PJS with small-bowel polyps that bidirectional DBE failed to reach and were ≧5 mm as shown by DBE enterography at our institution from May 2006 to April 2022 were retrospectively evaluated. The endpoint was the earliest occurrence of symptomatic intussusception induced by the polyp, endoscopic removal by repeat DBE or intraoperative endoscopy, or the last medical record describing the patient's condition. Results This study included 27 polyps in 13 patients. All patients had extraluminal adhesions. None developed symptomatic intussusception, eight patients underwent endoscopic removal at repeat DBE without surgery, two patients underwent removal with intraoperative endoscopy, two patients were observed without polyp removal, and one patient had a polyp removed at repeat DBE and three unreachable polyps remained. Repeat DBE without surgery was able to remove 14 polyps (52%). Polyps ≧15 mm included 11 lesions in eight patients and were observed for a median of 14 months without symptomatic intussusception. Conclusions The difficult-to-reach polyps may have a low risk of immediate symptomatic intussusception, possibly due to limited bowel mobility by extraluminal adhesions, and the likelihood of reaching them at repeat DBE was substantial. Hence, repeat DBE 1 year later may be proper in such patients with PJS.

Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Endoscopic treatment of intussusception due to small intestine polyps in patients with Peutz-Jeghers Syndrome.

Background and study aims Intussusception caused by intestinal polyps in patients with Peutz-Jeghers syndrome usually requires laparotomy. Patients following successful endoscopic reduction using double-balloon endoscopy (DBE) have been reported. The aim of this study was to evaluate the feasibility of endoscopic treatment of intussusception. Patients and methods We retrospectively reviewed patients who underwent DBE for intussusception due to small intestine polyps in patients with Peutz-Jeghers syndrome from January 2004 to June 2020. Results Twenty-seven (antegrade 22, retrograde 5) DBEs were performed in 19 patients with 25 sites of intussusception identified during the study period. If the intussusception remained once the endoscope reached the site, endoscopic reduction of the intussusception was performed as needed (15 sites). Ultimately, endoscopic resections (8 sites) or ischemic polypectomies (16 sites) of the polyp causing the intussusception were completed at 24 sites. Only one site could not be treated endoscopically and was treated surgically. The final per-site and per-patient success rates of endoscopic treatment were 96 % (24/25) and 95 % (18/19) respectively. Two patients developed mild acute pancreatitis and one patient developed intussusception after the procedures, both of which were treated non-operatively. Conclusions Endoscopic treatment of intussusception is feasible to avoid laparotomy in patients with Peutz-Jeghers syndrome.

Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice.

Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice.

Long-term changes in serum gastrin levels during standard dose vonoprazan therapy.

BACKGROUND: Long-term acid suppression during vonoprazan therapy causes hypergastrinemia which may induce gastric mucosal changes such as fundic gland and hyperplastic polyps. The aim of this study is to clarify the long-term changes in serum gastrin levels and risk factors for hypergastrinemia. METHODS: From July 2016 to April 2020, 48 patients receiving vonoprazan 10 mg once daily for more than one year were reviewed. Serum gastrin level was evaluated by radioimmunoassay in a fasting condition (reference range 37-172 pg/ml). RESULTS: The baseline median gastrin level was 100 (range, 54-415) pg/ml. The gastrin level over 4 years was 700-1200 pg/ml, which plateaued at 1.5 years. Multivariate analysis revealed factors associated with gastrin levels 12 months after starting vonoprazan and identified severe gastric atrophy as a significant positive risk factor (p = .046). The gastrin level over 4 years in patients with severe gastric atrophy and no atrophy was approximately 900-1500 and 500-1000 pg/ml, respectively. Female gender was also identified as a positive factor, although it was not statistically significant (p = .087). The gastrin level over 4 years in females was approximately 900-1300 pg/ml, greater than in males (500-900 pg/ml). CONCLUSION: A continued increase in gastrin levels was not found during long-term vonoprazan therapy. Severe gastric atrophy is a significant risk factor for hypergastrinemia.

Images of laser and light-emitting diode colonoscopy for comparing large colorectal lesion visibility with linked color imaging and white-light imaging.

OBJECTIVES: In light-emitting diode (LED) and laser colonoscopy, linked color imaging (LCI) superiority to white-light imaging (WLI) for polyp detection is shown separately. We analyzed the noninferiority of LCI between LED and laser colonoscopy and that of WLI (LECOL study). METHODS: We prospectively collected nonpolypoid lesions with WLI and LCI using LED and laser colonoscopy from January 2021 to August 2021. All images were evaluated randomly by 12 endoscopists (six nonexperts and six experts in three institutions) using the polyp visibility score: 4, excellent; 3, good; 2, fair; and 1, poor. The comparison score (LED better/similar/laser better) for redness and brightness was evaluated for WLI and LCI pictures of each lesion. RESULTS: Finally, 63 nonpolypoid lesions were evaluated, and the mean polyp size was 24.5 ± 13.4 mm. Histopathology revealed 13 serrated lesions and 50 adenomatous/cancerous lesions. The mean polyp visibility scores of LCI pictures were significantly higher than those of WLI in the LED (3.35 ± 0.85 vs. 3.08 ± 0.91, P < 0.001) and the laser (3.40 ± 1.71 vs. 3.05 ± 0.97, P < 0.001) group, and the noninferiority of LCI pictures between LED and laser was significant (P < 0.001). The comparison scores revealed that the evaluation of redness and brightness (LED better/similar/laser better) were 26.8%/40.1%/33.1% and 43.5%/43.5%/13.0% for LCI pictures (P < 0.001) and 20.6%/44.3%/35.1% and 60.3%/31.7%/8.0% for WLI pictures (P < 0.001), respectively. CONCLUSION: The noninferiority of polyp visibility with WLI and LCI in LED and laser colonoscopy was shown. WLI and LCI of LED tended to be brighter and less reddish than those of laser.

Multicenter epidemiological survey of pneumatosis intestinalis in Japan.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome. METHODS: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion. RESULTS: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425). DISCUSSION: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis.

A pilot study of micro-CT-based whole tissue imaging (WTI) on endoscopic submucosal dissection (ESD) specimens.

Endoscopic submucosal dissection can remove large superficial gastrointestinal lesions in en bloc. A detailed pathological evaluation of the resected specimen is required to assess the risk of recurrence after treatment. However, the current method of sectioning specimens to a thickness of a few millimeters does not provide information between the sections that are lost during the preparation. In this study, we have produced three-dimensional images of the entire dissected lesion for nine samples by using micro-CT imaging system. Although it was difficult to diagnose histological type on micro-CT images, it successfully evaluates the extent of the lesion and its surgical margins. Micro-CT images can depict sites that cannot be observed by the conventional pathological diagnostic process, suggesting that it may be useful to use in a complementary manner.

The effect of proton pump inhibitors and vonoprazan on the development of 'gastric mucosal redness'.

The safety of long-term proton pump inhibitor (PPI) and vonoprazan (VPZ) use is a relatively recent concern. Gastric mucosal redness was reported as a VPZ-associated lesion in a previous study. The aim of this study was to investigate the prevalence and risk factors for gastric mucosal redness. Between December 2020 and November 2021, 1,101 patients who underwent esophagogastroduodenoscopy were reviewed. The cohort was divided into four groups: Control (n=580), histamine-2 receptor antagonist (H2RA) (n=65), PPI (n=146) and VPZ groups (n=310). Gastric mucosal redness was present in 48/1,101 patients (4%). The prevalence in controls, H2RA, PPI and VPZ groups was 1.9% (11/580), 1.5% (1/65), 6.2% (9/146) and 8.7% (27/310), respectively. Both the PPI and VPZ groups had a significantly higher prevalence of gastric mucosal redness compared with the control group (P<0.001). In the multivariate analysis, PPI and VPZ use were significantly associated with gastric mucosal redness. Fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, and stardust gastric mucosa were also significantly associated with PPI and VPZ use in the multivariate analysis. Back-to-back analysis showed that gastric mucosal redness was not seen before starting PPI/VPZ in most patients. The duration of treatment with VPZ was investigated to determine if it affected the prevalence of gastric mucosal redness. There were no significant differences in treatment duration among patients with and without gastric mucosal redness (mean ± standard deviation: 3.0±1.5 vs. 2.5±1.4 years, P=0.077). In conclusion, the prevalence of gastric mucosal redness was low but was associated with PPI and VPZ use.

Underwater Endoscopic Mucosal Resection of Small Rectal Neuroendocrine Tumors.

Background and Study Aims: The resection strategy for rectal neuroendocrine tumors (NET) < 10 mm is not uniform. We compared the utility of underwater endoscopic mucosal resection (UEMR) to endoscopic submucosal resection with a ligation device (ESMR-L) to resect rectal NETs. Patients and Methods: Patients with rectal NET < 10 mm treated with UEMR or ESMR-L were included. Their medical records were retrospectively reviewed. Results: Thirty-two patients were divided into a UEMR group (n = 7) and an ESMR-L group (n = 25). Histopathological diagnosis of NET by biopsy was known before resection in 43% (3/7) in the UEMR group and 68% (17/25) in the ESMR-L group, (p = 0.379). UEMR was performed on an outpatient basis for all patients, and 92% of ESMR-L (23/25) were performed as inpatient procedures (p < 0.001). The procedure time was significantly shorter in the UEMR group than in the ESMR-L group [median (IQR), min, 6 (5-8) vs. 12 (9-14), p = 0.002]. En bloc resection and R0 resection rates were 100% in both groups. Pathological evaluations were predominantly NET G1 in both groups (UEMR: 7/7, 100% and ESMR-L: 23/25, 92%). Two patients in the ESMR-L group developed delayed bleeding, controlled by endoscopic hemostasis. Device costs were significantly higher in the ESMR-L group than the UEMR group by approximately US$180 [median (IQR), $90.45 (83.64-108.41) vs. $274.73 (265.86-292.45), P < 0.001]. Conclusion: UEMR results in similar resection quality with shorter procedure time and lower costs compared to ESMR-L. We recommend UEMR for the resection of rectal NET < 10 mm.

Pathological Evaluation of Rectal Cancer Specimens Using Micro-Computed Tomography.

Whole-block imaging (WBI) using micro-computed tomography (micro-CT) allows the nondestructive reconstruction of a three-dimensional view of tissues, implying that WBI may be used for accurate pathological evaluation of patients with rectal cancer. HOWEVER, the clinical impact of this approach is unclear. We aimed to clarify the efficacy of WBI in the whole-mount specimens of locally advanced rectal cancer. A total of 237 whole-mount formalin-fixed paraffin-embedded blocks from 13 patients with rectal cancer who underwent surgical treatment were enrolled and scanned with micro-CT to generate three-dimensional images. WBI was evaluated following the conventional pathological review of the corresponding whole-slide imaging (WSI). WBI identified all tumor sites detected using WSI. Furthermore, WBI revealed one additional tumor site, which was not detected using WSI. Tumor resection margin was significantly closer to the soft-tissue edge when measured using WBI (7.7 mm vs. 6.6 mm, p < 0.01). Seventy-six percent of tumor deposits on WSI were changed according to the evidence of tumor interaction with the surrounding tissues confirmed using WBI. Furthermore, WBI revealed 25 additional lymph nodes, six of which were metastatic. The combination of conventional hematoxylin and eosin-stained imaging and WBI may contribute to an accurate pathological assessment.

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.

The pocket-creation method facilitates endoscopic submucosal dissection of gastric neoplasms involving the pyloric ring.

Background and study aims Endoscopic submucosal dissection (ESD) of superficial gastric lesions involving the pyloric ring is difficult. The pocket-creation method (PCM) with a small-caliber-tip transparent hood can overcome this difficulty by compressing the pyloric sphincter applying both traction and counter-traction. The aim of this study is to clarify the usefulness of the PCM for ESD of superficial gastric neoplasms involving the pyloric ring compared to the conventional method (CM). Patients and methods From October 2006 to August 2019, 66 gastric lesions requiring duodenal submucosal dissection beyond the pyloric ring in 66 patients were resected. The CM was mainly performed in the first period (CM group, n = 46) and the PCM in the second period (PCM group, n = 20). We retrospectively reviewed their medical records. Results Although no significant differences were observed in en bloc resection rates between the two groups, the PCM group had a significantly higher R0 resection rate than the CM group ( P  = 0.047). There were no holes in resected specimens in the PCM group while three specimens in the CM group had a hole. The dissection speed in the PCM group tended to be higher than in the CM group, although it did not reach statistical significance ( P  = 0.148). No significant differences were observed for the incidence of adverse events. Conclusions This is the first study reporting the advantages of the PCM over the CM for ESD of gastric lesions involving the pyloric ring. We believe that the PCM is an effective strategy to compress the pyloric sphincter and facilitates R0 resection.

Double-balloon endoscopy facilitates efficient endoscopic resection of duodenal and jejunal polyps in patients with familial adenomatous polyposis.

BACKGROUND : Many patients with familial adenomatous polyposis (FAP) have adenomatous polyps of the duodenum and the jejunum. We aimed to elucidate the long-term outcomes after double-balloon endoscopy (DBE)-assisted endoscopic resection of duodenal and jejunal polyps in patients with FAP. METHODS : We retrospectively reviewed patients who underwent more than two sessions of endoscopic resection using DBE from August 2004 to July 2018. RESULTS : A total of 72 DBEs were performed in eight patients (median age 30 years, range 12-53; 1.4 DBE procedures/patient-year) during the study period, and 1237 polyps were resected. The median observation period was 77.5 months (range 8-167). There were 11 adverse events, including seven delayed bleeds and four episodes of acute pancreatitis. No delayed bleeding occurred after cold polypectomy. Although, in one patient, one endoscopically resected duodenal polyp was diagnosed as being intramucosal carcinoma, none of the patients developed an advanced duodenal or jejunal cancer during the study period. CONCLUSIONS : Endoscopic resection of duodenal and jejunal polyposis using DBE in patients with FAP can be performed safely, efficiently, and effectively.

Endoscopic ischemic polypectomy for small-bowel polyps in patients with Peutz-Jeghers syndrome.

BACKGROUND: To decrease the risk of bleeding or perforation, ischemic polypectomy is performed using a detachable snare or endoclip with double-balloon endoscopy (DBE) for small-bowel polyps in patients with Peutz - Jeghers syndrome. The aim of this study was to determine the effectiveness and feasibility of ischemic polypectomy. METHODS: We retrospectively reviewed patients who underwent two or more sessions of ischemic polypectomy using DBE from July 2004 to August 2017. RESULTS: 67 therapeutic DBEs were performed in nine patients during the study period and 352 polyps were treated. The median observation period was 34 months (range 12 - 66). There was a declining trend over time in the median number of polyps > 15 mm treated per patient first DBE session 6, second 2, third 1.5, fourth 0.5, fifth 0.5; P = 0.11, Friedman test). No patient required laparotomy due to intussusception during the study period. One patient developed mild acute pancreatitis after the procedure. CONCLUSIONS: Ischemic polypectomy was feasible for the control of small-bowel polyps in patients with Peutz - Jeghers syndrome.

The pocket-creation method may facilitate endoscopic submucosal dissection of large colorectal sessile tumors.

Background and study aims Resecting large colorectal sessile tumors using endoscopic submucosal dissection (ESD) is challenging because of severe submucosal fibrosis. Previously, we reported that ESD strategy using the pocket-creation method (PCM) is useful for large colorectal sessile tumors, but there are no large studies reporting the effectiveness and safety of the PCM for resection of large colorectal sessile tumors. Patients and methods This was a retrospective review of 90 large colorectal sessile tumors in 89 patients who underwent ESD in our institution. Large colorectal sessile tumors were defined as polypoid lesions 20 mm or more in diameter. We divided them into PCM (n = 40) and conventional method (CM) groups (n = 50). The primary outcome measure was en bloc resection. The inverse-probability-treatment weighting (IPTW) approach was used to adjust for selection bias. Results Both PCM and CM achieved high en bloc resection (100 % vs. 94 %, non-adjusted P  = 0.25, IPTW-adjusted P  = 0.19) and R0 resection rates (88 % vs. 78 %, non-adjusted P  = 0.28, IPTW-adjusted P  = 0.27). When PCM was used, the rate of pathologically negative vertical margins was significantly greater than with the CM (IPTW-adjusted P  = 0.045). The dissection time was significantly shorter (IPTW-adjusted P  = 0.025) and dissection speed faster (IPTW-adjusted P  = 0.013) using the PCM than when the CM was used. There was no significant difference in the incidence of adverse events (intraprocedural perforation and delayed bleeding, IPTW-adjusted P  = 0.68). Conclusion Although en bloc resection and R0 resection rates were similar, PCM significantly increased the rate of negative vertical margins with rapid dissection for treatment of large colorectal sessile tumors.