Search

Background/Aims: To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC). Methods: Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings. Results: We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively. Conclusions: The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%. [ABSTRACT FROM AUTHOR]

Tumor sensitivity to platinum (Pt)‐based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency‐causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan‐cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan‐cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell‐free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events—BRCA1 (n = 3), BRCA2 (n = 18)—including eight pure deletions, one single‐nucleotide variant, six multinucleotide variants, and six deletion–insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology‐mediated end‐join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP‐inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt‐based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA‐associated cancers, our findings suggest that reversion mutations due to Pt‐chemotherapy might be correlated with BRCA1/2‐mediated tumorigenesis even in non‐BRCA‐associated histologies. [ABSTRACT FROM AUTHOR]

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation‐specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS‐FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS‐FNA cytology. [ABSTRACT FROM AUTHOR]

Background/aims: In stereomicroscopic sample isolation processing, the cutoff value (≥4 mm) of stereomicroscopically visible white cores indicates high diagnostic sensitivity. We aimed to evaluate endoscopic ultrasound-guided tissue acquisition (EUS-TA) using a simplified stereomicroscopic on-site evaluation of upper gastrointestinal subepithelial lesions (SELs)., Methods: In this multicenter prospective trial, we performed EUS-TA using a 22-gauge Franseen needle in 34 participants with SELs derived from the upper gastrointestinal muscularis propria, requiring pathological diagnosis. The presence of stereomicroscopically visible white core (SVWC) in each specimen was assessed using stereomicroscopic on-site evaluation. The primary outcome was EUS-TA's diagnostic sensitivity with stereomicroscopic on-site evaluation based on the SVWC cutoff value (≥4 mm) for malignant upper gastrointestinal SELs., Results: The total number of punctures was 68; 61 specimens (89.7%) contained stereomicroscopically visible white cores ≥4 mm in size. The final diagnoses were gastrointestinal stromal tumor, leiomyoma, and schwannoma in 76.5%, 14.7%, and 8.8% of the cases, respectively. The sensitivity of EUS-TA with stereomicroscopic on-site evaluation based on the SVWC cutoff value for malignant SELs was 100%. The per-lesion accuracy of histological diagnosis reached the highest level (100%) at the second puncture., Conclusion: Stereomicroscopic on-site evaluation showed high diagnostic sensitivity and could be a new method for diagnosing upper gastrointestinal SELs using EUS-TA.

Endoscopic retrograde cholangiopancreatography (ERCP) remains challenging in patients who have undergone surgical reconstruction of the intestine. Recently, many studies have reported that balloon-enteroscope-assisted ERCP (BEA-ERCP) is a safe and effective procedure. However, further improvements in outcomes and the development of simplified procedures are required. Percutaneous treatment, Laparoscopy-assisted ERCP, endoscopic ultrasound-guided anterograde intervention, and open surgery are effective treatments. However, treatment should be noninvasive, effective, and safe. We believe that these procedures should be performed only in difficult-to-treat patients because of many potential complications. BEA-ERCP still requires high expertise-level techniques and is far from a routinely performed procedure. Various techniques have been proposed to facilitate scope insertion (insertion with percutaneous transhepatic biliary drainage (PTBD) rendezvous technique, Short type single-balloon enteroscopes with passive bending section, Intraluminal injection of indigo carmine, CO2 inflation guidance), cannulation (PTBD or percutaneous transgallbladder drainage rendezvous technique, Dilation using screw drill, Rendezvous technique combining DBE with a cholangioscope, endoscopic ultrasound-guided rendezvous technique), and treatment (overtube-assisted technique, Short type balloon enteroscopes) during BEA-ERCP. The use of these techniques may allow treatment to be performed by BEA-ERCP in many patients. A standard procedure for ERCP yet to be established for patients with a reconstructed intestine. At present, BEA-ERCP is considered the safest and most effective procedure and is therefore likely to be recommended as first-line treatment. In this article, we discuss the current status of BEA-ERCP in patients with surgically altered gastrointestinal anatomy.

Aim: To evaluate short-type-single-balloon enteroscope (SBE) with passive-bending, high-force transmission functions for endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anastomosis., Methods: Short-type SBE with this technology (SIF-Y0004-V01; working length, 1520 mm; channel diameter, 3.2 mm) was used to perform 50 ERCP procedures in 37 patients with Roux-en-Y anastomosis. The rate of reaching the blind end, time required to reach the blind end, diagnostic and therapeutic success rates, and procedure time and complications were studied retrospectively and compared with the results of 34 sessions of ERCP performed using a short-type SBE without this technology (SIF-Y0004; working length, 1520 mm; channel diameter, 3.2 mm) in 25 patients., Results: The rate of reaching the blind end was 90% with SIF-Y0004-V01 and 91% with SIF-Y0004 (P = 0.59). The median time required to reach the papilla was significantly shorter with SIF-Y0004-V01 than with SIF-Y0004 (16 min vs 24 min, P = 0.04). The diagnostic success rate was 93% with SIF-Y0004-V01 and 84% with SIF-Y0004 (P = 0.17). The therapeutic success rate was 95% with SIF-Y0004-V01 and 96% with SIF-Y0004 (P = 0.68). The median procedure time was 40 min with SIF-Y0004-V01 and 36 min with SIF-Y0004 (P = 0.50). The incidence of hyperamylasemia was 6.0% in the SIF-Y0004-V01 group and 14.7% in the SIF-Y0004 group (P = 0.723). The incidence of pancreatitis was 0% in the SIF-Y0004-V01 group and 5.9% in the SIF-Y0004 group (P > 0.999). The incidence of gastrointestinal perforation was 2.0% (1/50) in the SIF-Y0004-V01 group and 2.9% (1/34) in the SIF-Y0004 group (P > 0.999)., Conclusion: SIF-Y0004-V01 is useful for ERCP in patients with Roux-en-Y anastomosis and may reduce the time required to reach the blind end.

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.

Aim: To evaluate the effectiveness of a short-type single-balloon-enteroscope (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a reconstructed intestine., Methods: Short-type SBE was developed to perform ERCP in postoperative patients with a reconstructed intestine. Short-type SBE is a direct-viewing endoscope with the following specifications: working length, 1520 mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE has a water-jet channel. The study group comprised 22 patients who underwent 31 sessions of short-type SBE-assisted ERCP from June 2011 through May 2012. Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8 sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the rate of reaching the blind end (papilla of Vater or choledochojejunal anastomosis), mean time required to reach the blind end, diagnostic success rate (defined as the rate of successfully imaging the bile and pancreatic ducts), therapeutic success rate (defined as the rate of successfully completing endoscopic treatment), mean procedure time, and complications., Results: Among the 31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1 min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic success rates in all patients and those with an intact papilla were respectively 86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The therapeutic success rates in all patients and those with an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and 92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel diameter was 3.2 mm, stone extraction could be performed with a wire-guided basket in 12 sessions, and wire-guided intraductal ultrasonography could be performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise in serum amylase levels to more than 3 times the upper limit of normal) occurred in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions) with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2 patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding. Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved after conservative treatment., Conclusion: Short-type SBE is effective for ERCP in patients with a reconstructed intestine and allows most conventional ERCP devices to be used.