Safety of biliary drainage with 6-mm metallic stent for preoperative obstructive jaundice in pancreatic cancer: PURPLE SIX STUDY.

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

Successful Response to Golimumab in a Case of Relapsing Polychondritis Overlapping with Ulcerative Colitis.

A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.

Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.

A 73-year-old woman was referred to our hospital for persistent liver dysfunction. When the patient was 45 years old, her youngest sister had been diagnosed with Wilson disease (WD). The patient therefore underwent several family screening tests, all of which were unremarkable. She had an annual medical checkup and was diagnosed with liver dysfunction and fatty liver at 68 years old. A liver biopsy and genetic testing were performed, and she was diagnosed with WD; chelation therapy was then initiated. In patients with hepatic disorders and a family history of WD, multiple medical examinations should be conducted, as the development of WD is possible regardless of age.

Primary Bile Duct Diffuse Large B-cell Lymphoma Diagnosed by Repeated Endoscopic Ultrasound-guided Fine-needle Aspiration and Endoscopic Retrograde Cholangiopancreatography.

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

Evaluation of the Jichi Medical University diverticular hemorrhage score in the clinical management of acute diverticular bleeding with emergency or elective endoscopy: A pilot study.

BACKGROUND AND AIMS: Emergency endoscopic hemostasis for colonic diverticular bleeding is effective in preventing serious consequences. However, the low identification rate of the bleeding source makes the procedure burdensome for both patients and providers. We aimed to establish an efficient and safe emergency endoscopy system. METHODS: We prospectively evaluated the usefulness of a scoring system (Jichi Medical University diverticular hemorrhage score: JD score) based on our experiences with past cases. The JD score was determined using four criteria: CT evidence of contrast agent extravasation, 3 points; oral anticoagulant (any type) use, 2 points; C-reactive protein ≥1 mg/dL, 1 point; and comorbidity index ≥3, 1 point. Based on the JD score, patients with acute diverticular bleeding who underwent emergency or elective endoscopy were grouped into JD ≥3 or JD <3 groups, respectively. The primary and secondary endpoints were the bleeding source identification rate and clinical outcomes. RESULTS: The JD ≥3 and JD <3 groups included 35 and 47 patients, respectively. The rate of bleeding source identification, followed by the hemostatic procedure, was significantly higher in the JD ≥3 group than in the JD <3 group (77% vs. 23%, p <0.001), with a higher JD score associated with a higher bleeding source identification rate. No significant difference was observed between the groups in terms of clinical outcomes, except for a higher incidence of rebleeding at one-month post-discharge and a higher number of patients requiring interventional radiology in the JD ≥3 group than in the JD <3 group. Subgroup analysis showed that successful identification of the bleeding source and hemostasis contributed to a shorter hospital stay. CONCLUSION: We established a safe and efficient endoscopic scoring system for treating colonic diverticular bleeding. The higher the JD score, the higher the bleeding source identification, leading to a successful hemostatic procedure. Elective endoscopy was possible in the JD <3 group when vital signs were stable.

Covered self-expandable metallic stents versus plastic stents for endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction.

BACKGROUND/AIMS: Covered self-expandable metallic stents (cSEMS) have become popular for endoscopic ultrasound-guided hepaticogastrostomy with transmural stenting (EUS-HGS). We compared the time to recurrent biliary obstruction (TRBO), complications, and reintervention rates between EUS-HGS using plastic stent (PS) and cSEMS in patients with unresectable malignancies at multicenter institutions in Japan. METHODS: Patients with unresectable malignant biliary obstruction who underwent EUS-HGS between April 2015 and July 2020 at any of the six participating facilities were enrolled. Primary endpoint: TRBO; secondary endpoints: rate of complications other than recurrent biliary obstruction and technical success rate of reintervention were evaluated. RESULTS: PS and cSEMS were used for EUS-HGS in 109 and 43 patients, respectively. The TRBO was significantly longer in the cSEMS group than in the PS group (646 vs. 202 days). Multivariate analysis identified two independent factors associated with a favorable TRBO: combined EUS-guided antegrade stenting with EUS-HGS and the use of cSEMS. No significant difference was observed in the rate of complications other than recurrent biliary obstruction between the two groups. The technical success rate of reintervention was 85.7% for PS and 100% for cSEMS (p=0.309). CONCLUSION: cSEMS might be a better option for EUS-HGS in patients with unresectable malignancies, given the longer TRBO.

A case of needle tract seeding that seemed to be caused by endoscopic ultrasound-guided fine-needle aspiration.

A 66-year-old man underwent a single endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) session and distal pancreatectomy for the pancreatic body adenocarcinoma measuring 12 mm in diameter. At 3 years after surgery, we diagnosed needle tract seeding (NTS) and performed total gastrectomy. NTS can occur with small tumors or after a single session of EUS-FNA.

The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy.

Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.

Utility of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for diagnosing small subepithelial lesions (< 20 mm).

AIM: Subepithelial lesions (SELs) are defined as being located under the mucosa. Presently, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is commonly performed to diagnose SELs. With the development of new puncture needles, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB), which allows for the acquisition of large tissue samples, has been proposed. However, studies on EUS-FNB of SELs measuring < 20 mm have not yielded satisfactory results. Therefore, we aimed to assess the performance and usefulness of EUS-FNB of SELs measuring less than < 20 mm. METHODS: The present study included 62 patients who underwent EUS-FNA or EUS-FNB for SELs at our hospital between January 2015 and March 2019. EUS-FNA was performed using fine-needle aspiration needles, and EUS-FNB was performed using fine-needle biopsy needles. These needles, which come in different shapes and diameters, were compared in terms of their usefulness in performing procedures for SELs measuring ≥ 20 mm and those measuring < 20 mm. RESULTS: For SELs measuring ≥ 20 mm, the use of needles with a large diameter, such as 19 or 20 G, resulted in significantly improved diagnostic rates. For SELs measuring < 20 mm, the use of FNB needles showed significantly improved diagnostic rates, regardless of the size of the puncture needles. CONCLUSION: Even when SELs are less than 20 mm, they might have malignant potential, and histological diagnosis may be desirable in some cases. EUS-FNB has an advantage over EUS-FNA in the diagnosis of SELs measuring < 20 mm.

A Comparative Study of Endoscopic Ultrasonography and Histopathology Images for the Diagnosis of Early Chronic Pancreatitis.

OBJECTIVE: The concept of early chronic pancreatitis (ECP) and its diagnostic criteria were first proposed by Japan, using endoscopic ultrasonography (EUS) findings for diagnosis. However, these findings have not been supported by pathological findings. We aimed to examine the association between the EUS and pathological findings of the same area of the pancreas. METHODS: In 12 patients who underwent pancreaticoduodenectomy for distal bile duct cancer without accompanying pancreatitis, a comparative analysis between preoperative EUS and pathological findings was performed. The part of the pancreas adjoining the portal vein was evaluated. RESULTS: In 7 cases, abnormal EUS findings included in the diagnostic criteria for ECP were seen; the correlation of the accuracy of lobularity seen on EUS compared with the pathological findings of the pancreatic parenchyma (inflammatory cell infiltration, atrophy of acinar cells, and fibrosis) was high (83.3%-91.7%). Pancreatic duct findings revealed that the accuracy of the hyperechoic margin of the pancreatic duct on EUS compared with pathological findings (wall thickness of pancreatic duct) was high (83.3%). CONCLUSIONS: Endoscopic ultrasonography findings for ECP, according to Japan's 2019 revised criteria, lobularity, and the hyperechoic margin of the pancreatic duct may highly correspond to the pathological findings of chronic inflammation.

Investigation of the Indications for Endoscopic Papillectomy and Transduodenal Ampullectomy for Ampullary Tumors.

OBJECTIVE: The standard treatment for ampullary tumors is pancreaticoduodenectomy. However, minimally invasive procedures such as endoscopic papillectomy (EP) and transduodenal ampullectomy (TDA) have recently gained popularity. Therefore, we aimed to evaluate the effectiveness of these minimally invasive procedures for ampullary tumors. METHODS: We conducted a retrospective study of 42 patients who underwent either EP or TDA for ampullary tumors between June 2011 and November 2020. RESULTS: We found that in patients with significantly larger tumors, TDA was often selected. Patients who underwent EP had significantly shorter hospital stays. No significant differences were observed regarding procedural accidents, tumor size, and recurrence. CONCLUSION: No differences were observed regarding the treatment outcomes of EP and TDA except hospital stay. EP is less invasive and can be the initial choice of procedure. TDA is performed when EP is not technically feasible. No significant relationship was noted between tumor size and recurrence, and careful observation of the patient's postoperative course is required.

[A case of gastric hamartomatous inverted polyp (GHIP), preoperatively diagnosed based on EUS findings].

We report the case of a patient with a gastric hamartomatous inverted polyp (GHIP) and discuss the relevant literature. A 65-year-old woman was referred to our hospital because of a slow-growing pedunculated polyp measuring 30mm in diameter, present in the greater curvature of the fundic region of the stomach. It was covered with normal gastric mucosa, and the top was reddish. A biopsy specimen taken from the reddish area;it showed inflamed gastric mucosa with hyperplastic and mildly distorted foveolar glands. Abdominal contrast computed tomography showed a protruding tumor that was unevenly enhanced and contained multiple cystic lesions inside. Endoscopic ultrasonography (EUS, Olympus GIF-UCT260) showed a heterogeneous tumor with multiple anechoic or low-echoic cystic lesions, originating from the second or third layer of the stomach wall. The patient had no clinical symptoms, no family history, and no laboratory data abnormalities. Based on these findings, we diagnosed her with GHIP. As the polyp had shown an increase in size (5mm/5 years) and about 20% of GHIPs were reported to coexist with precancerous or cancerous lesions, we performed endoscopic polypectomy. The tumor was histologically characterized by submucosal growth of hypertrophic glands with cystic dilatation, accompanied by smooth muscle proliferation, branching from the bundles. Thus, the final diagnosis was GHIP. Though GHIP is a rare and basically benign polyp, the rate with gastric cancer was reported to be relatively high. EUS findings are important for the diagnosis and when GHIP is suspected, the lesion requires to be monitored closely. If there are some signs that suggest a malignancy (growth, changes in surface mucosa, etc.), endoscopic en bloc resection or surgical resection should be considered.

Introduction of gastric endoscopic submucosal dissection and skill acquisition in a regional hospital.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is standard treatment for early gastric cancer. With aging of the population in Japan being more pronounced in rural areas, the availability of ESD at regional hospitals is becoming important. Here, we assessed the learning curve of one physician for skill acquisition in gastric ESD. METHODS: The subjects were 34 patients (38 lesions) who underwent gastric ESD at a regional hospital between October 2014 and March 2017 and 15 patients (15 lesions) who underwent the procedure at a university hospital between April 2017 and April 2018. The resection periods of the first 19 lesions and subsequent 19 lesions at the regional hospital were defined as the first and seconds periods, and the resection period of 15 lesions at the university hospital was defined as the third period. The learning curve across the three periods was assessed using the cumulative sum analysis method. RESULTS: The resection speed in the first, second, and third periods were 6.4 ± 4.1, 6.9 ± 3.4, and 9.4 ± 5.4 mm2/min, respectively (not significant). The slope of the learning curve began to increase at the 30th patient. The en bloc resection and curative resection rates did not differ significantly among the three periods. There were no serious procedure-related complications. CONCLUSION: This study showed that the introduction of gastric ESD at a regional hospital is possible, and that a certain skill level was acquired by the 30th patient. Furthermore, with careful patient selection, favorable results can be obtained and procedural safety ensured.

Rupture of Hepatic Pseudoaneurysm Formed Nine Years after Carbon Ion Radiotherapy for Hepatocellular Carcinoma.

An 83-year-old man with a history of carbon ion radiotherapy for hepatocellular carcinoma nine years ago presented to a primary care hospital with a fever and abdominal pain. He underwent computed tomography, which revealed the rupture of a hepatic pseudoaneurysm close to the fiducial marker for carbon ion radiotherapy and bleeding into the bile duct. He was successfully treated with transcatheter arterial embolization. Thereafter, re-rupture occurred from a site proximal to the first rupture, and this was treated similarly. It is necessary to be alert for not only tumor recurrence but also pseudoaneurysm occurrence after carbon ion radiotherapy.

Appropriate Timing of Discontinuation of Tacrolimus Therapy for Refractory Ulcerative Colitis.

BACKGROUND AND OBJECTIVES: Tacrolimus is very effective at inducing remission in patients with refractory ulcerative colitis. However, the optimal time-point for the discontinuation of tacrolimus is controversial because administration of tacrolimus for > 3 months is currently not approved for insurance reimbursement in Japan. We conducted this study to determine the optimal time of discontinuation of tacrolimus in patients with ulcerative colitis. METHODS: Of 38 patients who received tacrolimus as remission induction therapy for refractory active ulcerative colitis between 2009 and 2018, this study included 21 patients who received tacrolimus for ≥ 3 months before being switched to thiopurines. These patients were divided into two groups for analysis: the confirmed switch (CS) group (n = 13), in which tacrolimus was switched to azathioprine after endoscopic confirmation of mucosal improvement, and the mandatory switch (MS) group (n = 8), in which tacrolimus was switched to a thiopurine agent without endoscopic confirmation of improvement. RESULTS: The relapse rates after the switch to azathioprine were 23% and 88% in the CS and MS groups, respectively (p = 0.0075). No patient of the CS group underwent surgery, while 50% of patients of the MS group underwent surgery (p = 0.0117). The cumulative event-free rates at 6 months, 1 year, and 2 years were 92%, 92%, and 65%, respectively, in the CS group and 15%, 15%, and 0%, respectively, in the MS group (p < 0.0001). The incidence rate of adverse reactions was 31% in the CS group and 13% in the MS group, but there were no serious adverse reactions. CONCLUSIONS: It seems preferable to discontinue tacrolimus after endoscopic confirmation of mucosal healing. However, attention should be paid to the potential occurrence of adverse reactions associated with long-term tacrolimus therapy.

A Diagnostically Challenging Case of Autoimmune Pancreatitis Due to Contamination of the Pathological Specimen with Early Gastric Cancer.

A 73-year-old man with worsened diabetes underwent abdominal computed tomography and was diagnosed with localized enlargement of the pancreatic tail. Based on the suspicion of autoimmune pancreatitis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. A cytologic examination showed findings suggestive of adenocarcinoma. Due to discrepancies between the imaging and pathological findings, esophagogastroduodenoscopy was performed. An extensive early gastric cancer lesion was detected in the posterior wall of the gastric corpus. It was therefore likely that puncturing through the tumor resulted in the contamination with cancer tissue. The possibility of a concomitant malignancy should be considered in EUS-FNA, and thorough examinations should be conducted.