Remaining Issues Related to Serum Cytokines in Patients with Unresectable Hepatocellular Carcinoma Treated by Atezolizumab plus Bevacizumab Combination Treatment.

INTRODUCTION: Atezolizumab plus bevacizumab (AteBev) combination treatment is widely used as first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). We aimed to clarify therapeutic issues regarding serum cytokines and the immune reaction in patients with uHCC treated with AteBev. METHODS: We analyzed preserved serum from a previous prospective study on adult Japanese patients with chronic liver disease and uHCC who received AteBev treatment at our hospital. In that study, AteBev were administered intravenously every 3 weeks, and blood samples were collected before and after 3 weeks' treatment. Dynamic computed tomography was performed after 6 weeks of treatment to assess response. RESULTS: In the prospective study, 21 of the 59 patients showed partial response (PR) and 19 patients showed stable disease (SD), but 19 patients showed progressive disease (PD). We found that serum levels of tumor necrosis factor-alpha, interleukin (IL)-6, and soluble IL-2 receptor (IL-2R) increased significantly in the PR group, but only soluble IL-2R increased significantly in the PD group. Regulatory T cells decreased significantly in the PD group, but there was no significant change in Th1 or Th2 cells from before to after treatment in any group. As regards soluble MHC-class I, pre-treatment levels were significantly lower in the PD group than in the PR group, and serum levels increased significantly with treatment in the PD group. CONCLUSION: These findings reveal a need to further improve T-cell priming and to further make T-cells recognize tumor antigens in uHCC.

Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

[Epstein-Barr virus-associated gastritis with perigastric lymphadenopathy accompanied by infectious mononucleosis:a case report].

A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.

Effects of Lenvatinib on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Previously, we reported that the tyrosine kinase inhibitor (TKI) sorafenib decreases serum levels of carnitine and reduces skeletal muscle volume. Moreover, others reported that TKIs might lead to cardiomyopathy or heart failure. Therefore, this study aimed to evaluate the effects of lenvatinib (LEN) on skeletal muscle volume and cardiac function in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study included 58 adult Japanese patients with chronic liver diseases and HCC treated with LEN. Blood samples were collected before and after 4 weeks of treatment, and serum carnitine fraction and myostatin levels were measured. Before and after 4-6 weeks of treatment, the skeletal muscle index (SMI) was evaluated from computed tomography images and cardiac function was assessed by ultrasound cardiography. RESULTS: After treatment, SMI, serum levels of total carnitine, and global longitudinal strain were significantly lower, but serum levels of myostatin were significantly higher. Left ventricular ejection fraction showed no significant change. CONCLUSION: In patients with HCC, LEN decreases serum levels of carnitine, skeletal muscle volume, and worsens cardiac function.

Genotype-phenotype correlation of small-intestinal polyps on small-bowel capsule endoscopy in familial adenomatous polyposis.

BACKGROUND AND AIMS: In familial adenomatous polyposis (FAP), neoplastic lesions outside the colon have become increasingly important. The genotype-phenotype correlation has been established for duodenal polyps, and regular screening is recommended. However, this correlation remains unclear for small-intestinal lesions, except for reports on the relationship between their occurrence and Spigelman stage. Here, we used small-bowel capsule endoscopy (SBCE) to investigate the genotype-phenotype correlation of small-intestinal polyps in FAP. METHODS: The genotype-phenotype correlation of small-intestinal polyps was investigated in patients with FAP who underwent SBCE, Esophagogastroduodenoscopy (EGD), and adenomatous polyposis coli (APC) gene analysis. Of 64 patients with FAP who underwent SBCE, 41 were included in the final analysis, 4 did not undergo a complete small intestine examination, and 19 did not undergo genetic analysis. RESULTS: The prevalence (median number) of small-intestinal polyps by Spigelman stage was 26% (1.5), 0% (0), 44% (5), 60% (4), and 73% (25.5) for stages 0 to IV, respectively. Significantly more small-intestinal polyps were found in Spigelman stage III and IV groups than in the stage 0 group (P < .05). The APC variant was negative for 6 patients (15%), and the sites associated with more than 5 small-intestinal polyps were codons 278, 1062, 1114, 1281, 1307, 1314, and 1504. CONCLUSIONS: In FAP patients, SBCE surveillance is potentially recommended for patients with pathogenic variants in the APC gene at codons 278 and 1062 to 1504 or with Spigelman stage III or higher.

Focal pancreatic ductal change induced by 10-Fr S-type plastic stent in chronic pancreatitis.

BACKGROUND AND AIM: Stent-induced ductal change (SIDC) is a complication of endoscopic pancreatic stenting (EPS) in patients with chronic pancreatitis (CP). However, the evaluation of SIDC associated with S-type pancreatic plastic stent (PS) and large-caliber PS, such as 10 Fr, is limited. This study aimed to analyze the SIDC of the main pancreatic duct (MPD) associated with 10-Fr S-type PS in patients with CP. METHODS: Between January 2008 and December 2021, 132 patients with CP in whom a 10-Fr S-type PS had been installed by EPS were retrospectively reviewed. The SIDC incidence rate was examined, and the clinical features of patients with and without SIDC were investigated, including the outcomes for detected SIDC. RESULTS: Stent-induced ductal change during EPS was confirmed in 41 patients (31.1%) of 132 patients at a site coincident with the PS tip or distal flap in the MPD. All patients were asymptomatic during the development of SIDC. Morphological changes in the MPD were detected as elevated (75.6%) or bearing stricture changes (24.4%). A total of 90.2% of SIDC developed after the first 10-Fr PS installation. No significant differences were noted between the patients with and without SIDC. The outcomes of continued PS installment for SIDC showed persistence and secondary change. CONCLUSIONS: Stent-induced ductal change-associated 10-Fr PS installation was performed in just under one-third of the patients, indicating a substantial incidence rate and a possible development of SIDC from early stages onwards. More emphasis should be placed on SIDC as the complication.

Clinical practice guidelines for endoscopic papillectomy.

The Japan Gastroenterological Endoscopy Society has developed the "Clinical Practice Guidelines for Endoscopic Papillectomy (EP)" as a fundamental guideline using scientific approach. EP is a recently spreading therapeutic modality for ampullary tumors ranked as high risk endoscopic technique. Because of the paucity of high level of evidence, strength of recommendations had to be determined by a consensus among specialists. These guidelines, shed light on the following five issues: Indications, Preoperative/intraoperative preparations and techniques, Early adverse events, Therapeutic outcomes and remnants/recurrences, and Follow-up and late adverse events, to guide current clinical practice on EP.

[A case of unresectable advanced gastric cancer with oral mucosal necrosis during combination therapy with nab-paclitaxel plus ramucirumab].

A 61-year-old patient with advanced gastric cancer was treated with ramucirumab plus albumin-suspended paclitaxel as second-line treatment. The treatment resulted in exposure of the right mandible around an implant. The implant was removed, and sequestration was not observed. The patient was diagnosed with oral mucosal necrosis. Thus, implants may cause mucosal necrosis due to angiogenesis inhibitors.

Gallbladder wall thickening in patients with IgG4-related diseases, with special emphasis on IgG4-related cholecystitis.

OBJECTIVES: Gallbladder (GB) wall thickening sometimes occurs in patients with autoimmune pancreatitis (AIP), a condition for which the name, IgG4-related cholecystitis, was proposed. We examined the radiological findings of the GB in patients with IgG4-related diseases and clinical features of patients with GB wall thickening and presented a hypothesis of its pathogenesis. MATERIALS AND METHODS: GB wall thickening was defined by thickness ≥ 4 mm. GB wall thickness was examined in 258 patients with IgG4-related disease. Clinical and imaging findings of 200 patients with AIP with and without GB wall thickening were then compared. RESULTS: GB wall thickening was detected in 58 patients (29%) with AIP and two patients with isolated IgG4-related sclerosing cholangitis. In the 60 GBs examined, wall thickening was diffuse, with the walls possessing a smooth inner surface. No GB wall thickening was detected among the 56 patients with IgG4-related disease without AIP or IgG4-related sclerosing cholangitis. Bile duct stenosis was detected in 56 patients (97%) with AIP with GB wall thickening. Intraductal ultrasonography indicated cystic duct wall thickening connected to bile duct wall thickening in 11 of 14 (79%) patients with AIP or IgG4-related sclerosing cholangitis with GB wall thickening. Forty-eight patients in whom IgG4-related cholecystitis was diagnosed experienced resolution of the GB wall thickening after receiving steroid therapy. CONCLUSIONS: Most cases of GB wall thickening in IgG4-related diseases are closely associated with IgG4-related sclerosing cholangitis and may be a manifestation of IgG4-related disease throughout the biliary tract, including the bile duct, cystic duct, and GB.

Usefulness of Magnifying Endoscopy with Narrow-Band Imaging for Diagnosing Mixed Poorly Differentiated Gastric Cancers.

INTRODUCTION: Curative rates of endoscopic treatment for undifferentiated-type early gastric cancer (EGC), particularly mixed poorly differentiated adenocarcinoma (MIXED-POR), are lower than those of endoscopic treatment for the differentiated type. Magnifying endoscopy with narrow-band imaging (ME-NBI) is useful for diagnoses of the histological type. This study aimed to investigate the detection rates of MIXED-POR among undifferentiated-type EGCs using biopsy and ME-NBI in order to improve curative rates through endoscopic treatment. METHODS: We analyzed 267 lesions initially subjected to endoscopic submucosal resection (ESD) and histologically diagnosed as undifferentiated-type EGCs between July 2005 and December 2016 at our hospital. We obtained written informed consent from all participants. Biopsy and ME-NBI findings were compared to distinguish pure signet ring cell carcinoma (PURE-SIG) and MIXED-POR. ME-NBI findings were divided into 2 categories depending on the presence of irregular vessels. Results of biopsy and ME-NBI (combination method) were also analyzed, and detection rates of MIXED-POR and PURE-SIG were evaluated in terms of sensitivity, specificity, and accuracy. RESULTS: Overall, 114 lesions were analyzed. Fifty-eight lesions (50.9%) were identified as MIXED-POR. With biopsy, the detection rate of MIXED-POR was significantly lower than that of PURE-SIG (p < 0.0001). ME-NBI detected significantly more MIXED-POR with irregular vessels than PURE-SIG (p < 0.0001). The combination method could detect significantly more MIXED-POR than PURE-SIG (p < 0.0001). The sensitivity and accuracy for MIXED-POR diagnosis were significantly higher with the combination method than with biopsy alone (p < 0.0001). DISCUSSION/CONCLUSION: Combining biopsy and ME-NBI improved the accuracy of pretreatment diagnosis before ESD in undifferentiated-type cancer.

Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan.

OBJECTIVES: Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population. METHODS: From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model. RESULTS: Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%). CONCLUSIONS: This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.

[A case of diverticulitis in the horizontal part of the duodenum].

A 38-year-old woman was referred to our department to investigate epigastric discomfort. Laboratory studies showed increases in the peripheral white blood cell count and the level of C-reactive protein. Abdominal computed tomography depicted inflammation and a mass in the horizontal part of the duodenum. To observe it directly, we performed esophagogastroduodenoscopy (EGD), but it was very difficult to reach the lesion. Therefore, we performed enteroscopy by using SIF-H290S (Olympus Europa SE & Co. KG, Hamburg, Germany), which revealed a diverticulum containing food residue in the horizontal part of the duodenum. Using grasping forceps, we removed the food residue. The patient recovered over the next several days. Endoscopic therapy was thus effective for duodenal diverticulitis caused by food residue, but attention to technique was necessary.

Tivantinib Decreases Hepatocyte Growth Factor-Induced BCRP Expression in Hepatocellular Carcinoma HepG2 Cells.

Tivantinib, a mesenchymal-epithelial transition factor (cMET) inhibitor, is a molecular targeting drug that kills hepatocellular carcinoma (HCC) cells. Tivantinib alone does not affect the overall survival of patients with HCC, and combination treatment with tivantinib and other therapies has not been evaluated. This study was conducted to clarify the effect of the tivantinib in regulating breast cancer therapy-resistant protein (BCRP), a key transporter of 5-fluorouracil (5-FU), and dihydropyridine dehydrogenase (DPYD), a major metabolic enzyme of 5-FU. To this end, cMET gene expression was determined by RT-PCR in HepG2 (human hepatoma) cells. The transcriptional start sites of BCRP were determined by 5'-rapid amplification of cDNA ends (5'-RACE). BCRP and DPYD mRNA levels were determined by real-time RT-PCR, and promoter activities were measured by dual-luciferase assays. Results show that hepatocyte growth factor (HGF) upregulated the mRNA level of BCRP, but not DPYD, in HepG2 cells. The upregulation of BCRP expression by HGF was down-regulated by tivantinib. We also identified two transcriptional start sites (E1α, E1ß) in BCRP by 5'-RACE. The transcriptional activity of the region -287 to E1α of BCRP was upregulated by HGF, which was decreased by tivantinib, whereas activity of the region -297 to E1ßo f BCRP was not affected by tivantinib. Therefore, tivantinib regulates BCRP expression upstream of exon 1α. Combination treatment of tivantinib and 5-FU should be further evaluated for HCC therapy.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staff need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with the relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.

Immunohistochemical analysis of tumor budding as predictor of lymph node metastasis from superficial esophageal squamous cell carcinoma.

BACKGROUND: Tumor budding is known predictors of lymph node metastasis from esophageal squamous cell carcinoma. However, it is not easy to detect such small cell clusters on hematoxylin-eosin (HE) staining. Therefore, we evaluated tumor budding using immunohistochemistry (IHC) for epithelial cell markers. METHOD: We analyzed tumor budding in 50 cases of superficial esophageal squamous cell carcinoma. We evaluated the impact of clinicopathological factors and tumor budding to predict lymph node metastasis. A total of 565 tumor sections were assessed using HE staining and IHC for cytokeratin 5/6. RESULTS: Based on receiver operating characteristic curves, the cut-off values for high-grade tumor budding evaluated using HE staining or IHC were 2 and 11, respectively. High-grade tumor budding evaluated using HE staining (P = 0.007) and IHC (P ≤ 0.001) were significantly correlated with lymph node metastasis. For tumors with pT1a-MM to pT1b-SM1, high-grade tumor budding evaluated using IHC was correlated with lymph node metastasis (P = 0.050). CONCLUSIONS: Tumor budding was significantly associated with lymph node metastasis. The optimal cut-off values of tumor budding on HE staining and tumor budding on IHC were 2 and 11, respectively. Even though both tumor budding on HE staining and tumor budding on IHC were significantly associated with lymph node metastasis, tumor budding on IHC tend to be more associated with lymph node metastasis.

Clinicopathological characteristics and frequency of multiple rectal neuroendocrine tumors: a single-center retrospective study.

BACKGROUND: Rectal multiple neuroendocrine tumors (M-NETs) are rare, with only few epidemiologic reports on the topic. Therefore, their clinicopathological features are not completely known, and the appropriate treatment strategy has not been established. PURPOSE: This study aimed to compare the clinicopathological malignant potential (lymphatic or venous invasion-positive and lymph node metastasis rates) of M-NETs with that of solitary NETs (S-NETs). METHODS: We retrospectively investigated 369 patients with NETs of the rectum. Patients who underwent colonoscopy at the Cancer Institute Hospital between January 1979 and 2016 and diagnosed with S-NETs were included, and S-NETs were found in 348 patients. Patients with M-NETs were classified into two groups as follows: patients with < 8 tumors (several (S) group, n = 21) and those with ≥ 8 tumors (numerous (N) group, n = 3). RESULTS: The overall frequency of M-NETs was 5.7% and that of the N group was 0.8%. The mean tumor diameter in the N group was 6.0 mm (range, 4-8 mm). The lymphatic invasion rates of the S-NETs, and S and N groups of the M-NETs were 8.9%, 5.6%, and 66.7%, respectively. Moreover, the lymph node metastasis rates were 9.2%, 11.1%, and 33.3, respectively. CONCLUSIONS: While M-NETs in the S and N groups had different characteristics, they were rarer in the N group. The N group may have higher rates of lymphatic invasion and lymph node metastasis regardless of tumor size.

A Prospective Multicenter Study of a Fully Covered Metal Stent in Patients with Distal Malignant Biliary Obstruction: WATCH-2 Study.

BACKGROUND: Both fully covered (FC) and partially covered (PC) self-expandable metal stents (SEMSs) are now commercially available for distal malignant biliary obstruction (MBO). While FCSEMS can be easily removed at the time of re-interventions, it is theoretically prone to migration. However, few comparative data between FC and PC SEMSs have been reported. AIMS: The aim of this study was to compare clinical outcomes of FCSEMS with those of PCSEMS. METHODS: This was a multicenter, prospective study of FCSEMS for unresectable distal MBO with a historical control of PCSEMS, which was previously reported as the WATCH study. The primary outcome was recurrent biliary obstruction (RBO), and secondary outcomes were stent migration, stent removal, stent-related adverse events, and survival. RESULTS: A total of 151 cases with unresectable distal MBO undergoing FCSEMS placement were enrolled and compared with a historical cohort of 141 cases undergoing PCSEMS placement. No significant differences were found in the rate of RBO (29 vs. 33%; P = 0.451), time to RBO (318 vs. 373 days; P = 0.382), and survival (229 vs. 196 days; P = 0.177) between FCSEMS and PCSEMS. The rate of stent migration also did not differ significantly between the two groups (14 vs. 8%; P = 0.113). The removal of FCSEMSs was successful in all 24 attempted cases (100%). CONCLUSIONS: FCSEMSs appeared comparable to PCSEMSs in terms of RBO without a significant increase in stent migration rate in patients with unresectable distal MBO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000007131.

Japan Gastroenterological Endoscopy Society guidelines for endoscopic papillary large balloon dilation.

The Japan Gastroenterological Endoscopy Society has developed the 'EPLBD Clinical Practice Guidelines' as fundamental guidelines based on new scientific techniques. EPLBD is a treatment method that has recently become widely used for choledocolithiasis. The evidence level in this field is usually low, and in many instances, the recommendation grading has to be determined on the basis of expert consensus. At this point, the guidelines are divided into the following six sections according to the 'EST Clinical Practice Guidelines': (i) Indications, (ii) procedures, (iii) special cases, (iv) procedure-related adverse events, (v) treatment outcomes, and (vi) postoperative follow up observation.

Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn's Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography.

BACKGROUND & AIMS: Previous studies have not found a correlation between fecal level of calprotectin and small bowel Crohn's disease (CD). However, these studies evaluated patients mainly by ileocolonoscopy, which views up to only the terminal ileum rather than entire small intestine. We investigated whether level of fecal calprotectin (FC) is a marker of active CD of the small bowel, identified by balloon-assisted enteroscopy and computed tomography enterography (CTE). METHODS: We performed a prospective study of 123 patients with CD (35 with ileitis, 72 with ileocolitis, and 16 with colitis) evaluated by balloon-assisted enteroscopy from May 2012 through July 2015 at Toho University Sakura Medical Centre in Japan. Patients with strictures detected by balloon-assisted enteroscopy were evaluated by CTE (n = 17). Fecal samples were collected from each patient, and levels of calprotectin were measured; patient demographic variables and medical history were also collected. We developed a CTE scoring system for disease severity that was based on bowel wall thickness, mural hyperenhancement, and engorged vasa recta. The association between level of FC and simple endoscopic index for CD score or CTE was evaluated by using Spearman rank correlation coefficient. RESULTS: Level of FC correlated with the simple endoscopic index for CD score (r = 0.6362, P < .0001), even in patients with only active disease of the small intestine (r = 0.6594, P = .0005). In the 17 patients with strictures that could not be passed with the enteroscope, CTE detected all lesions beyond the strictures as well as areas in the distal side of the strictures. Level of FC correlated with CTE score in these patients (r = 0.4018, P = .0011, n = 63). In receiver operating characteristic analyses, the FC cutoff value for mucosal healing was 215 µg/g; this cutoff value identified patients with healing with 82.8% sensitivity, 71.4% specificity, positive predictive value of 74.3%, negative predictive value of 80.6%, odds ratio of 12.0, and area under the receiver operating characteristic curve value of 0.81. CONCLUSIONS: A combination of measurement of level of FC and CTE appears to be effective for monitoring CD activity in patients with small intestinal CD, including patients with strictures that cannot be passed by conventional endoscopy.