Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD).

BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD]. RESULTS: Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities. CLINICAL TRIALS REGISTRY: University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

Bile duct MALT lymphoma diagnosed with direct cholangioscopy: a case report.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) extremely rarely arise in extrahepatic biliary tract. Here, we report a case of bile duct MALT lymphoma diagnosed with direct cholangioscopy. The patient was an 80-year-old female with history of esophageal cancer, and had been occasionally treated with balloon dilatation for anastomotic stricture. She was referred to our hospital for treatment of choledocholithiasis. Since transesophageal endoscope insertion was impossible, stone extraction by transjejunal approach was performed. When gastroduodenoscope was directly inserted to the bile duct (direct cholangioscopy), accidentally two flat lesions with development of large atypical vessels in hilar region were noted. Biopsy revealed diffuse infiltration of CD20 positive small- to medium-sized atypical lymphocytes. A diagnosis of bile duct MALT lymphoma was made. The patient underwent eight courses of chemotherapy with rituximab alone, with no evident complications. Although biliary tract MALT lymphoma is rare, advances in cholangioscopy may promote encounter with such lesions. Accumulation of endoscopic figures of biliary tract MALT lymphoma is required.

Characteristics of adult patients newly diagnosed with Crohn's disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn's disease in Japan (iCREST-CD).

BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.

Precision cancer genome testing needs proficiency testing involving all stakeholders.

To implement precision oncology, analytical validity as well as clinical validity and utility are important. However, proficiency testing (PT) to assess validity has not yet been systematically performed in Japan. To investigate the quality of next-generation sequencing (NGS) platforms and cancer genome testing prevalent in laboratories, we performed pilot PT using patient samples. We prepared genomic DNA from the cancer tissue and peripheral blood of 5 cancer patients and distributed these to 15 laboratories. Most participating laboratories successfully identified the pathogenic variants, except for two closely located KRAS variants and 25 bp delins in EGFR. Conversely, the EGFR L858R variant was successfully identified, and the allele frequency was similar for all the laboratories. A high DNA integrity number led to excellent depth and reliable NGS results. By conducting this pilot study using patient samples, we were able to obtain a glimpse of the current status of cancer genome testing at participating laboratories. To enhance domestic cancer genome testing, it is important to conduct local PT and to involve the parties concerned as organizers and participants.

[A case of pancreatic actinomycosis diagnosed by EUS-FNA].

A 60-year-old male patient had alcoholic chronic pancreatitis. Three months prior, he had undergone an exchange of pancreatic duct stents. In December 201X-1, magnetic resonance imaging and computed tomography (CT) scan results showed a caput pancreatic mass and common bile duct dilatation. We considered that it was because of chronic pancreatitis and decided to follow up by imaging studies. Further, in March 201X, a CT scan result revealed worsening of the mass and bile duct dilation. We assessed the mass by endoscopic ultrasound and fine-needle aspiration. Histological findings revealed to an interstitial tissue infiltrated by several neutrophils and plasma cells and abscess-forming inflammation like sulfur granule. The mass was improved by antibiotic administration for 6 months.

Usefulness of endoscopic metal stent placement for malignant afferent loop obstruction.

BACKGROUND: Malignant afferent loop obstruction (mALO) can cause cholangitis, pancreatitis, and perforation due to blind loop dilatation. However, peritoneal dissemination, lymph node metastasis, and recurrence of the tumor are the main causes of mALO, and most cases are in the advanced stage with thoracicoabdominal fluid retention, for which surgery and percutaneous transhepatic treatment are challenging. At our hospital, endoscopic metal stent placement (EMSP) has been applied for such mALO. We retrospectively investigated the usefulness of EMSP for mALO. METHODS: We conducted a retrospective analysis of 11 mALO patients with EMSP between January 2008 and December 2018. The following items were evaluated: the characteristics of patients, technical success and adverse events of EMSP, clinical efficacy, and outcome after EMSP. RESULTS: The surgical procedures and reconstruction methods were distal gastrectomy with Billroth II reconstruction for 3 patients, pancreaticoduodenectomy with modified-Child reconstruction for 7, choledochojejunostomy with Roux-en-Y reconstruction for 1. The cause of mALO was peritoneal dissemination for 6 patients, local recurrence for 3, lymph node metastasis for 1, and afferent loop invasion for 1. EMSP was attempted in 13 sessions for 11 patients, and successful in 12 of 13 sessions. There were no adverse events. The clinical efficacy was high in successful EMSP. The median survival time after EMSP was 118 days. Ten patients died of primary disease and one patient died of uncontrollable cholangitis after the failure of EMSP. mALO recurred and EMSP was repeated for 2 of 10 patients who died of primary disease. CONCLUSIONS: The success rate of EMSP for mALO was high in patients with poor general conditions due to advanced-stage malignant tumors and it was able to be safely performed, suggesting its high clinical efficacy. The incidence of mALO recurrence after EMSP was low.

Successful biliary self-expandable metallic stenting using an ultra-slim endoscope for cholangitis caused by pancreatic cancer.

Highlight Kida and colleagues described their method for successfully performing biliary self-expandable metallic stenting with the through-the-scope technique using an ultra-slim endoscope for malignant biliary obstruction with duodenal stenosis. This procedure may be useful in cases of duodenal stenosis in which it is difficult to reach the major duodenal papilla.

Phase II clinical trial of second-line weekly paclitaxel plus trastuzumab for patients with HER2-positive metastatic gastric cancer.

BACKGROUND: Combination therapy with fluorouracil, platinum, and trastuzumab (Tmab) is the first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, and there is currently no established second-line therapy. We evaluated the efficacy and safety of weekly paclitaxel plus Tmab as second-line chemotherapy for HER2-positive gastric cancer patients. PATIENTS AND METHODS: Eligible patients were older than or equal to 20 years, had histologically confirmed gastric adenocarcinoma that was HER2 positive (immunohistochemistry 3+ or immunohistochemistry 2+ and fluorescence in-situ hybridization positive or dual color in-situ hybridization positive), and had been treated previously with chemotherapy (pretreated or not with Tmab). Patients received weekly paclitaxel plus Tmab as the second-line chemotherapy. The primary endpoint was the overall response rate (ORR; threshold ORR=20% and expected ORR=35%). RESULTS: Twenty-eight patients were enrolled. ORR was 21.4%. The median progression-free survival (PFS) was 4.6 months. The median overall survival (OS) was 9.6 months. No significant differences were observed in ORR, PFS, or OS between the Tmab beyond progression (TBP) group (n=20) and the non-TBP group (n=8). However, in the TBP group, a therapeutic effect was associated with the duration of PFS in the first-line Tmab treatment [≥6 months PFS in the first-line Tmab treatment (n=10) vs. <6 months (n=10); ORR: 40 and 10%, P=0.303, PFS: 6.2 and 2.8 months, P=0.005, OS: 15.8 and 6.5 months, P=0.006, respectively]. CONCLUSION: Weekly paclitaxel plus Tmab was not superior as second-line chemotherapy for HER2-positive gastric cancer patients, but may be effective for patients who showed better responses to Tmab-combined chemotherapy in the first-line treatment.

Pancreatic acinar cell carcinoma with extensive tumor embolism at the trunk of portal vein and pancreatic intraductal infiltration.

A 59-year-old man was admitted to the hospital with acute pancreatitis. The cause was suggested to be a pancreatic tumor based on computed tomography (CT). The pancreatic tumor was 45 mm with an extensive tumor embolism at the trunk of the portal vein and intraductal infiltration of the main pancreatic duct (MPD). The pancreatic tumor was diagnosed as acinar cell carcinoma (ACC) by endoscopic ultrasound guided fine needle aspiration. Therefore, the cause of acute pancreatitis was diagnosed to be intraductal infiltration of ACC in the MPD. Chemotherapy was initially performed because it was difficult to perform surgery due to extensive tumor embolism at the trunk of the portal vein. Degeneration and reduction of ACC and tumor embolism of the portal vein was noted on CT after chemotherapy, and extended distal pancreatectomy with portal vein reconstruction was performed. There has been no relapse for 5 years postoperative follow-up. This is an interesting and rare case because ACC with intraductal infiltration of MPD is low in frequency; most ACCs are asymptomatic when they are found, and many cases tend to have poor prognosis in spite of surgical cases.

A unique case of massive gastrointestinal bleeding.

OBJECTIVES: Lipomas are the second most common benign tumors of the small bowel, and most lipomas are asymptomatic. However, lipomas with diameters of >20 mm tend to be symptomatic, for example, to cause bleeding, obstructive jaundice, abdominal pain, intestinal obstruction, intussusception, and/or perforation. METHODS/RESULTS: We report a case of massive gastrointestinal bleeding from a jejunal lipoma combined with intussusception. A preoperative diagnosis of gastrointestinal bleeding derived from a jejunal lipoma combined with intussusception was made based on double-balloon enteroscopy and contrast-enhanced computed tomography, and partial resection of the small intestine was performed. After surgery, there was no additional gastrointestinal bleeding. CONCLUSION: There have only been a few reports about cases of jejunal lipoma involving simultaneous bleeding and intussusception. Double-balloon enteroscopy is useful for preoperatively diagnosing bleeding from a lipoma. Our case highlights that jejunal lipoma can cause massive unexplained gastrointestinal bleeding.

Gastric adenocarcinoma of the fundic gland (chief cell-predominant type): A review of endoscopic and clinicopathological features.

Gastric adenocarcinoma of the fundic gland (chief cell-predominant type, GA-FG-CCP) is a rare variant of well-differentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.

Gastric adenocarcinoma of fundic gland type: Five cases treated with endoscopic resection.

Recently, a new disease entity termed gastric adenocarcinoma of fundic gland type (GA-FG) was proposed. We treated five cases of GA-FG with endoscopic submucosal dissection. All tumors were small and located in the upper third of the stomach. Four tumors were macroscopically identified as 0-IIa and one was identified as 0-IIb. Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder. All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion. Lymphatic invasion was seen only in one case, while no venous invasion was recognized. All tumors were positive for pepsinogen-I  and MUC6 by immunohistochemistry. None showed p53 overexpression, and the labeling index of Ki-67 was low in all cases. All cases have been free from recurrence or metastasis. Herein, we discussed the clinicopathological features of GA-FG in comparison with past reports.

A pedunculated polyp-shaped small-bowel lymphangioma causing gastrointestinal bleeding and treated by double-balloon enteroscopy.

We report a rare case of a small-bowel lymphangioma causing massive gastrointestinal (GI) bleeding that we successfully diagnosed and treated using double-balloon enteroscopy (DBE). An 81-year-old woman suffering from repeated GI bleeding of unknown origin underwent a capsule endoscopy at a previous hospital. She was suspected of having bleeding from the jejunum, and was referred to our department for diagnosis and treatment. An oral DBE revealed a 20 mm × 10 mm, regularly surfaced, white to yellowish, elongated, pedunculated jejunal polyp with small erosions at 10 cm distal to the ligament of Treiz. Since no other source of bleeding was identified by endoscopy in the deep jejunum, an endoscopic polypectomy (EP) was performed for this lesion. A subsequent histopathological examination of the resected polyp showed clusters of lymphatic vessels with marked cystic dilatation in the submucosa and the deep layer of the lamina propria mucosae. These characteristics are consistent with the typical features of small-bowel lymphangioma with erosions. Although clipping hemostasis was performed during EP, re-bleeding occurred. Finally, a complete hemostasis was achieved by performing an additional argon plasma coagulation.

[A case of hepatocellular carcinoma showed the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology using the cell block technique for differential diagnosis of gastric submucosal tumor].

A mass lesion presenting difficulty in differential diagnosis between a tumor in the lateral segment of the liver and a gastric submucosal tumor (SMT) was found in a 59-year-old man with chronic hepatitis B. For differential diagnosis between the 2 lesions, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was performed. EUS showed a tumor exhibiting a mosaic pattern with a halo derived from the lateral segment of the hepatic left lobe in contact with the stomach. FNA using the cell block technique revealed findings consistent with HCC. No examination-associated complications developed. In patients with HCC that is in contact with the stomach and shows extrahepatically protruding growth, which is difficult to differentiate from gastric SMT, EUS-FNA is a method worthy of trying.

A case of pancreatic cancer with formation of a mass mimicking alcoholic or autoimmune pancreatitis in a young man. Possibility of diagnosis by hypermethylation of pure pancreatic juice.

CONTEXT: Mass-forming pancreatitis can be divided into two distinct types: alcoholic and autoimmune. There have been some cases of an ambiguous diagnosis although care was taken to differentiate between alcoholic mass-forming pancreatitis, focal type autoimmune pancreatitis and pancreatic cancer. CASE REPORT: We report a case of pancreatic cancer mimicking alcoholic or autoimmune pancreatitis with the formation of a mass in a 32-year-old man with a history of heavy drinking. Although both serum immunoglobulin G and immunoglobulin G4 levels were normal, many serum auto-antibodies, including the antinuclear antibody, were detected. After he stopped drinking, abdominal computed tomography showed a pancreatic head mass 28 mm in diameter with little and weak enhancement in the early and delayed phases, respectively. Endoscopic retrograde cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and marked stenosis of the lower common bile duct. Although a percutaneous ultrasound-guided pancreatic biopsy demonstrated no evidence of autoimmune pancreatitis, he was treated with prednisolone to test the efficacy of steroid therapy. However, the pancreatic mass became enlarged after steroid therapy, and he underwent surgery during which the mass was found to be pancreatic cancer. Although the patient was treated with gemcitabine, he died 5 months after surgery. We retrospectively assessed DNA hypermethylation in the patient's pure pancreatic juice obtained on admission. We observed hypermethylation of the cancer-specific gene tissue factor pathway inhibitor 2 (TFPI2). CONCLUSION: This finding suggests that if the DNA hypermethylation of pure pancreatic juice had been assayed before steroid therapy, it would have supported the diagnosis of pancreatic cancer, and steroid therapy could have been avoided.