A novel endoscopic technique using fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy: the saddle-cross technique (with video).

BACKGROUND: In recent years, the number of patients with hepaticojejunostomy anastomotic strictures has increased. Balloon dilation and placement of multiple plastic stents have proven effective for hepaticojejunostomy anastomotic strictures. However, for refractory strictures, there is often a need for repeated endoscopic procedures within a short period. This study aimed to assess the efficacy and safety of the new saddle-cross technique, which uses two fully covered self-expandable metallic stents. METHODS: This was a retrospective analysis of 20 patients with benign hepaticojejunostomy anastomotic strictures who underwent placement of two fully covered self-expandable metallic stents at the National Cancer Center, Japan, from November 2017 to June 2021. RESULTS: The technical and clinical success rates were 100% (20/20). The median time of the procedure was 61 (range 25-122) min. The scheduled stent removal rate was 70% (14/20). Spontaneous dislodgement of the stent was observed on computed tomography in five patients (25.0%). The non-restenosis rate 12 months after the saddle-cross technique was 88.2% (15/17). Procedure-related early adverse events included mild ascending cholangitis in three patients (15.0%) and sepsis in one patient (5.0%). Procedure-related late adverse events included mild ascending cholangitis in three patients (15.0%) and bile duct hyperplasia in one patient (5.0%). CONCLUSIONS: The saddle-cross technique performed using two fully covered self-expandable metallic stents resulted in promising long-term stricture resolution with a high technical success rate. Based on these findings, the saddle-cross method can be considered an option for the standard procedure for benign hepaticojejunostomy anastomotic strictures.

A prospective multicenter study of endoscopic ultrasound-guided fine needle biopsy using a 22-gauge Franseen needle for pancreatic solid lesions.

BACKGROUND AND AIM: While encouraging data of endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) using a 22-gauge Franseen needle have been reported, large-scale data of per pass and quantitative analyses are still lacking. METHODS: This was a multicenter prospective study of EUS-FNB using the 22-gauge Franseen needle for a pancreatic solid lesion. Cytological and histological analyses per pass were evaluated and semi-quantitative analyses were performed on core tissue and blood contamination. Primary end-point was diagnostic accuracy per session. Prognostic factors were analyzed for diagnostic accuracy, sensitivity, core tissue, and blood contamination. RESULTS: A total of 629 passes were performed in 244 cases at 14 centers between 2018 and 2019. The median tumor size was 29 mm, and the puncture was transduodenal in 43%. The median pass number was 2. Diagnostic accuracy per session, at a first pass, and per pass were 93%, 90%, and 88%. In 198 cases with pancreatic cancer, diagnostic sensitivity per session, at a first pass, and per pass were 94%, 89%, and 89%. The rates of core tissue score of 4 and blood contamination score of 3 were 50% and 47%. The adverse event rate was 1.6%. In the multivariate analysis, tumor size ≤20 mm (odds ratio [OR] of 0.46, P = 0.03), transduodenal puncture (OR of 0.53, P = 0.04), and suction (OR of 0.16, P = 0.01) were associated with lower diagnostic accuracy. CONCLUSIONS: The EUS-FNB using the 22-gauge Franseen needle for pancreatic solid lesions showed high per pass and overall diagnostic accuracy.

Pancreatic Ductal Adenocarcinoma: Epidemiology and Risk Factors.

The number of new cases of pancreatic ductal adenocarcinoma is increasing with a cumulative total of 495,773 cases worldwide, making it the fourteenth most common malignancy. However, it accounts for 466,003 deaths per year and is the seventh leading cause of cancer deaths. Regional differences in the number of patients with pancreatic ductal adenocarcinoma appear to reflect differences in medical care, as well as racial differences. Compared to the prevalence of other organ cancers in Japan, pancreatic ductal adenocarcinoma ranks seventh based on the number of patients, eighth based on morbidity, and fourth based on the number of deaths, with a continuing increase in the mortality rate. Risk factors for developing pancreatic ductal adenocarcinoma include family history, genetic disorders, diabetes, chronic pancreatitis, and intraductal papillary mucinous neoplasms. An issue that hinders improvement in the prognosis of patients with pancreatic ductal adenocarcinoma is the development of a strategy to identify patients with these risk factors to facilitate detection of the disease at a stage when intervention will improve survival.

The Diagnosis of Autoimmune Pancreatitis Using Endoscopic Ultrasonography.

Autoimmune pancreatitis (AIP) is characterized by enlargement of the pancreas and irregular narrowing of the main pancreatic duct. It is often associated with IgG4-related sclerosing cholangitis (IgG4-SC), in which the bile duct narrows. Although characteristic irregular narrowing of the pancreatic duct caused by endoscopic retrograde cholangiopancreatography is noted in AIP, it is difficult to differentiate between localized AIP and pancreatic carcinoma based on imaging of the pancreatic duct. While stenosis of the bile duct in IgG4-SC is characterized by longer-length stenosis than in cholangiocarcinoma, differentiation based on bile duct imaging alone is challenging. Endoscopic ultrasound (EUS) can characterize hypoechoic enlargement of the pancreas or bile duct wall thickening in AIP and IgG4-SC, and diagnosis using elastography and contrast-enhanced EUS are being evaluated. The utility of EUS-guided fine needle aspiration for the histological diagnosis of AIP has been reported and is expected to improve diagnostic performance for AIP. Findings in the bile duct wall from endoscopic retrograde cholangiopancreatography followed by intraductal ultrasonography are useful in differentiating IgG4-SC from cholangiocarcinoma. Diagnoses based on endoscopic ultrasonography play a central role in the diagnosis of AIP.

Recurrent intestinal inflammation with a perianal abscess is not always Crohn's disease: a patient with a complex Meckel's diverticulum diagnosed by double-balloon endoscopy.

Recurrent intestinal inflammation and refractory perianal abscesses are typical manifestations of Crohn's disease. However, these conditions are not always due to Crohn's disease. A 25-year-old male with recurrent perianal abscesses for 1 year, suspected to be due to Crohn's disease, was referred for further evaluation. Computed tomography scan showed a perianal abscess abutting the small intestine. A complicated Meckel's diverticulum was suspected based on these findings. Meckel's diverticulum scintigraphy was negative. Bidirectional double-balloon endoscopy (DBE) identified a long diverticulum in the ileum. In this long diverticulum, a tight stricture was seen 5 cm distal to the diverticular opening. A selective contrast study showed a 10 cm diverticulum distal to the stricture, with three strictures in the long diverticulum. Inflammation of the Meckel's diverticulum due to bacterial overgrowth was suspected as a cause of the refractory perianal abscesses. Laparoscopic diverticulectomy was performed, and the specimen showed a 10 cm diverticulum containing post-inflammatory changes with scar formation. The perianal abscess was confirmed to be caused by an inflamed Meckel's diverticulum. The patient has been asymptomatic for 6 years after resection. DBE before exploratory laparotomy should be considered to investigate the cause of an abscess that could be secondary to small intestinal pathology.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Esophageal seeding after endoscopic ultrasound-guided fine-needle aspiration of a mediastinal tumor.

Background and study aims Tumor seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is rare. A 53-year-old man underwent transesophageal EUS-FNA for diagnosis of a 6-cm mass in the mediastinum as seen by computed tomography (CT). Four weeks later, repeat CT scan revealed a mass in the esophageal wall. Upper gastrointestinal endoscopy confirmed a lesion in the mid-esophagus, which was biopsied and found to be consistent with needle tract seeding after EUS-FNA. Tumor seeding in the gastrointestinal wall or peritoneum after EUS-FNA is rare, but may adversely affect the prognosis. Indications for EUS-FNA must be carefully considered.

Multiple orifices and cholangiography with a "fire-like" appearance after Kasai hepatoportoenterostomy for biliary atresia.

A 21-year-old female underwent a Kasai hepatoportoenterostomy with Roux-en-Y reconstruction for typeIII biliary atresia at age 63 days. At the age of 19 years, she developed cholangitis and CT scan revealed hepatolithiasis. She presented for treatment of the intrahepatic stone and the hepatportoenterostomy was directly visualized with double-balloon endoscopy (DBE). Endoscopic findings showed multiple intrahepatic bile ducts open to the jejunum through multiple orifices. Cholangiography showed narrowing of intrahepatic bile duct branches with a "fire-like" appearance. These findings have not been previously reported, since endoscopic approaches to patients with a hepaticojejunostomy were limited. DBE was useful to directly visualize the anastomosis in a patient status-post the Kasai operation for biliary atresia with a Rouxen-Y reconstruction.

Endoscopic diagnosis of extrahepatic bile duct carcinoma: Advances and current limitations.

The accurate diagnosis of extrahepatic bile duct carcinoma is difficult, even now. When ultrasonography (US) shows dilatation of the bile duct, magnetic resonance cholangiopancreatography followed by endoscopic US (EUS) is the next step. When US or EUS shows localized bile duct wall thickening, endoscopic retrograde cholangiopancreatography should be conducted with intraductal US (IDUS) and forceps biopsy. Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity. In patients with papillary type bile duct carcinoma, three biopsies are sufficient. In patients with nodular or infiltrating-type bile duct carcinoma, multiple biopsies are warranted, and IDUS can compensate for the limitations of biopsies. In preoperative staging, the combination of dynamic multi-detector low computed tomography (MDCT) and IDUS is useful for evaluating vascular invasion and cancer depth infiltration. However, assessment of lymph nodes metastases is difficult. In resectable cases, assessment of longitudinal cancer spread is important. The combination of IDUS and MDCT is useful for revealing submucosal cancer extension, which is common in hilar cholangiocarcinoma. To estimate the mucosal extension, which is common in extrahepatic bile duct carcinoma, the combination of IDUS and cholangioscopy is required. The utility of current peroral cholangioscopy is limited by the maneuverability of the "baby scope". A new baby scope (10 Fr), called "SpyGlass" has potential, if the image quality can be improved. Since extrahepatic bile duct carcinoma is common in the Far East, many researchers in Japan and Korea contributed these studies, especially, in the evaluation of longitudinal cancer extension.

A case of intraductal papillary mucinous neoplasms after recurrent acute pancreatitis.

We report a case of main pancreatic duct (MPD)-type intraductal papillary mucinous neoplasms of the pancreas (IPMNs), in whom diagnostic imaging modalities showed abnormal findings after 4 episodes of acute pancreatitis. The patient was 51 years old at his first admission for acute pancreatitis. He experienced two more episodes of acute pancreatitis, though repeated computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) showed no abnormality to explain the cause of the pancreatitis. After 3½ years from his first episode of pancreatitis, CT and endoscopic ultrasonography revealed pancreatic duct dilation of the pancreas head. Seven years after the first admission, a second ERCP and intraductal ultrasonography revealed a partially dilated MPD with papillary tumors. He underwent pancreaticoduodenectomy, and the pathological diagnosis was intraductal papillary mucinous adenoma with moderate atypia. This case suggests that acute pancreatitis can precede visualized IPMNs. Therefore, acute recurrent pancreatitis with unknown etiology should be followed up for the possibility of IPMNs, in order to detect neoplastic changes in the early stage to provide a better prognosis for the patient.

Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas containing foci of early carcinoma: correlations with cathepsin D expression and other malignant features.

BACKGROUND: Cathepsin D (CD) is an aspartyl lysosomal protease, and the prognostic value of CD expression has been studied in a variety of tumors, however, its role in early adenocarcinomas remains unclear. AIM OF THE STUDY: We evaluated the expression of CD in a series of colorectal adenomas with severe dysplasia containing foci of early carcinoma and compared the results to several histopathological and immunohistochemical features. METHODS: Adenomas were obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33 adenomas contained well-differentiated adenocarcinomas and nine adenomas contained moderately differentiated adenocarcinomas. RESULTS: Positive CD expressions were observed in 25% of well-differentiated adenocarcinomas and in 66.7% of moderately differentiated adenocarcinomas (p < 0.05). Of the 12 adenocarcinomas with positive CD expression, four had positive CD expression in their adenomas (p < 0.01), 6 showed positive Ki-67 expression in their adenomas (NS), and 10 had positive p53 expression in their adenomas (p < 0.05). No significant association was seen between the level of CD expression and adenoma size. CONCLUSIONS: The expression of CD in adenocarcinoma correlated significantly with differentiation, and with the levels of CD and p53 expression in the adenomas of the polyp.

Effectiveness of doxifluridine (5'-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens.

A 58-year-old man was diagnosed as having type 3 gastric cancer (poorly differentiated adenocarcinoma). He underwent total gastrectomy with splenectomy, as well as D3 dissection, and received postoperative chemotherapy combining oral uracil and futrafur (UFT) with cisplatin (CDDP), but results showed recurrence of multiple abdominal lymph node metastases around the aorta. He therefore received various anticancer drug regimens (irinotecan [CPT-11]/CDDP; 1 M tegafur-0.4 M gimeracil-1 M oteracil potassium [TS-1], methotrexate (MTX)/5-fluorouracil); however, final results showed growth of lymph node metastasis and simultaneous worsening of his general condition. The patient then received combined administration of doxifluridine (5'-DFUR)/docetaxel (5'-DFUR, 1000 mg/body [666.7 mg/m(2)], given by consecutive daily administration, orally, for days 1-14; and docetaxel, 80 mg/body [60 mg/m(2)], on day 8, by venous drip, every 3 weeks). Three courses of this regimen resulted in approximately 90% reduction of the abdominal lymph node size, disappearance of the right cervical lymph node metastasis, reductions of the levels of two tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA]19-9), and improvement of his general condition. In total, seven courses of the regimen were carried out. The patient died on day 298 after starting this combined regimen and showed a response period of 126 days. The primary toxicity identified was neutropenia (grade 4), as well as other low-grade (grade 1, 2) hematological and nonhematological toxicities. In the field of gastric cancer treatment, especially for patients showing multiple resistance to anticancer drugs, an effective therapy is critically needed.