Optimization of endoscopic ultrasound-guided tissue sample acquisition for commercially available comprehensive genome profiling.

BACKGROUND AND AIM: Optimal tumor samples are crucial for successful analysis using commercially available comprehensive genomic profiling (CACGP). However, samples acquired by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are occasionally insufficient, and no consensus on the optimal number of needle passes required for CACGP exists. This study aimed to explore the optimal number of needle passes required for EUS-TA to procure an ideal sample fulfilling the prerequisite criteria of CACGPs. METHODS: Patients who underwent EUS-TA for solid masses between November 2019 and July 2021 were retrospectively studied. The correlation between the acquisition rate of an ideal sample and the number of needle passes mounted on a microscope slide was evaluated. Additionally, the factors predicting a successful analysis were investigated in patients scheduled for CACGP using EUS-TA-obtained samples during the same period. RESULTS: EUS-TAs using 22- and 19-gauge (G) needles were performed in 336 and 57 patients, respectively. There was a positive correlation between the acquisition rate and the number of passes using a 22-G needle (38.9%, 45.0%, 83.7%, and 100% for 1, 2, 3, and 4 passes, respectively), while no correlation was found with a 19-G needle (84.2%, 83.3%, and 85.0% for 1, 2, and 3 passes, respectively). The analysis success rate in patients with scheduled CACGP was significantly higher with ideal samples than with suboptimal samples (94.1% vs 55.0%, P < 0.01). CONCLUSIONS: The optimal estimated number of needle passes was 4 and 1-2 for 22- and 19-G needles, respectively.

[Successful portal vein stent placement for chronic portal vein stenosis 5 years after pancreatoduodenectomy:a case report].

A 73-year-old man underwent pancreatoduodenectomy 5 years previously, and portal vein stenosis was observed immediately after surgery. A collateral vein with varices around the hepaticojejunostomy gradually developed. The patient experienced repeated episodes of melena that required transfusion. Enteroscopy confirmed varices around the hepaticojejunostomy, caused by portal vein stenosis, which was the source of intestinal bleeding. Varices were treated by placing an expandable metallic stent in the stenotic portal vein through a percutaneous transhepatic route. Although the portal vein stenosis was severe, the guidewire was successfully maneuvered into the superior mesenteric vein and stent placement was successful. Subsequently, the collateral vein disappeared and no further melena was observed.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Biliary obstruction and pancreatitis after duodenal stent placement in the descending duodenum: a retrospective study.

BACKGROUND: Metallic stents placed in the descending duodenum can cause compression of the major duodenal papilla, resulting in biliary obstruction and pancreatitis. These are notable early adverse events of duodenal stent placement; however, they have been rarely examined. This study aimed to assess the incidence of and risk factors for biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum. METHODS: We retrospectively reviewed data of consecutive patients who underwent metallic stent placement in the descending duodenum for malignant gastric outlet obstruction at a tertiary referral cancer center between April 2014 and December 2019. Risk factors for biliary obstruction and/or pancreatitis were analyzed using a logistic regression model. RESULTS: Sixty-five patients were included. Biliary obstruction and/or pancreatitis occurred in 12 patients (18%): 8 with biliary obstruction, 2 with pancreatitis, and 2 with both biliary obstruction and pancreatitis. Multivariate analysis indicated that female sex (odds ratio: 9.2, 95% confidence interval: 1.4-58.6, P = 0.02), absence of biliary stents (odds ratio: 12.9, 95% confidence interval: 1.8-90.2, P = 0.01), and tumor invasion to the major duodenal papilla (odds ratio: 25.8, 95% confidence interval: 2.0-340.0, P = 0.01) were significant independent risk factors for biliary obstruction and/or pancreatitis. CONCLUSIONS: The incidence of biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum was non-negligible. Female sex, absence of biliary stents, and tumor invasion to the major duodenal papilla were the primary risk factors. Risk stratification can allow endoscopists to better identify patients at significant risk and permit detailed informed consent.

Comparing the 14-mm uncovered and 10-mm covered metal stents in patients with distal biliary obstruction caused by unresectable pancreatic cancer: a multicenter retrospective study.

BACKGROUND: Endoscopic biliary drainage using metal stent (MSs) is an established palliative treatment for patients with unresectable malignant distal biliary obstruction (MDBO). However, a major drawback of MS is recurrent biliary obstruction (RBO). Uncovered MSs with a diameter of 14 mm (UMS-14) were developed to overcome this. We aimed to compare the clinical outcomes of UMS-14 with those of conventional covered MSs having a diameter of 10 mm (CMS-10). METHODS: Consecutive patients with MDBO caused by unresectable pancreatic cancer, who underwent UMS-14 or CMS-10 placement at two tertiary-care centers, were retrospectively examined according to the Tokyo Criteria 2014. RESULTS: Two hundred and thirty-eight patients who underwent UMS-14 (the UMS-14 group, n = 80) or CMS-10 (the CMS-10 group, n = 158) over a 62-month period were included. The technical and clinical success rates were similar between the two groups. RBO occurred in 20 (25%) and 59 (37%) patients of the UMS-14 and CMS-10 groups, respectively (p = 0.06). Median time till RBO was significantly longer in the UMS-14 group than in the CMS-10 group (not reached vs. 290 days, p = 0.04). Multivariate analysis revealed that CMS-10 placement was an independent risk factor for RBO (hazard ratio: 1.66, 95% confidence interval: 1.00-2.76). The incidence of early complications, including pancreatitis, and the overall survival (UMS-14 vs. CMS-10: 169 vs. 167 days, p = 0.83) were comparable between the two groups. CONCLUSIONS: UMS-14 stents were safe and effective for treating patients with MDBO secondary to unresectable pancreatic cancer. The insertion of UMS-14 is recommended, because it is less likely to get occluded as compared to CMS-10.

Macroscopic visible core length can predict the histological sample quantity in endoscopic ultrasound-guided tissue acquisition: Multicenter prospective study.

OBJECTIVES: Measurement of the macroscopic visible core (MVC) length during macroscopic on-site quality evaluation (MOSE) may allow estimation of sample adequacy for next-generation sequencing (NGS), and prediction of correct diagnosis in endoscopic ultrasound-guided tissue acquisition (EUS-TA) of pancreatic masses. METHODS: This multicenter prospective study included consecutive patients who underwent EUS-TA for pancreatic masses using a 22-G Franseen needle. MVC length and pathological samples obtained from two needle passes were analyzed on a per-pass basis. Outcome measures included respective correlations of MVC length with histological sample quantity and diagnostic yields. RESULTS: The analysis included 204 passes from 102 EUS-TAs. MVC length correlated positively with histological sample quantity (P < 0.01). On the receiver operating characteristic curve for MVC length, the cut-off value and area under the curve for obtaining a candidate sample for NGS were 30 mm and 0.74 (95% confidence interval [CI] 0.65-0.83), respectively. On multivariate analysis, MVC length ≥30 mm was a significant factor affecting suitability for NGS (odds ratio 6.19; 95% CI 2.72-14.10). Histologic diagnostic yield correlated positively with MVC length (P = 0.01); however, there was no positive correlation between MVC length and overall (histology plus cytology) diagnostic yield. CONCLUSIONS: Measuring MVC length to predict histological sample quantity on MOSE may be of clinical significance during EUS-TA using a 22-G Franseen needle. It may be an effective method, particularly while submitting samples for NGS. REGISTRATION: University Hospital Medical Information Network Trials Registry (UMIN000036528).

Efficacy of endoscopic samplings during initial biliary drainage for cases of pancreatic head cancer: United diagnostic yields of multiple pathological samplings.

BACKGROUND/OBJECTIVES: The diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been fully studied; however, the efficacy of other endoscopic samplings (OESs) is less clear. The aim of this study was to examine the diagnostic efficacies of OESs for pancreatic head cancer (PHC). METHODS: The diagnostic efficacies of endoscopic samplings were retrospectively analyzed in 448 PHC cases and 63 cases of mass-forming pancreatitis (MFP) during initial transpapillary biliary drainage. The OESs included duodenal biopsy (118 PHCs and 50 MFPs), biliary biopsy (218 and 51) with cytology (368 and 53), and pancreatic duct biopsy (23 and 13) with cytology (56 and 43). EUS-FNA was conducted in a different session (149 and 62). Factors associated with OES sensitivity were analyzed. The sensitivity of biliary biopsy was compared between 1.95 mm and 1.8 mm forceps. RESULTS: Cancer cells were confirmed in 87.9% of the EUS-FNA samplings and in 64.1% (268/418) obtained by combined OESs (average 1.7 OES types per case): 68.6% by duodenal biopsy, 59.6% by biliary biopsy, 32.6% by biliary cytology, 73.9% by pancreatic duct biopsy, and 33.9% by pancreatic duct cytology. No MFP cases revealed cancer by any sampling. OESs did not increase adverse events. Duodenal stenosis, serum bilirubin, tumor size, and pancreatic juice amounts were associated with OES sensitivity. Biliary biopsy had the same sensitivity with different forceps. CONCLUSION: EUS-FNA was the most diagnostic protocol; however, OESs can be safely applied during the initial biliary drainage to reduce the demand for EUS-FNA while providing good diagnostic yields.

Comparison of five-phase computed tomography images of type 1 autoimmune pancreatitis and pancreatic cancer: Emphasis on cases with atypical images.

BACKGROUND/OBJECTIVES: International consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images. METHODS: Five-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items. RESULTS: ICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase. CONCLUSIONS: Ordinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. "Delayed enhancement" is characteristic to ordinary AIPs, however, "pancreatic-phase enhancement" is more diagnostic for atypical AIPs.

Can regular follow-up imaging contribute to the determination of appropriate timing of surgery in patients with undiagnosed mucinous cystic neoplasm? A multicenter retrospective study.

OBJECTIVE: Guidelines suggest that patients with undiagnosed pancreatic cystic lesions should be monitored despite a lack of evidence supporting surveillance for undiagnosed mucinous cystic neoplasms (MCNs). We aimed to investigate the pre- and post-operative clinical course of patients with MCN and the utility of follow-up for patients who were not diagnosed with MCN at initial examination. PATIENTS AND METHODS: This multicenter retrospective study enrolled 28 patients with resected pathology-proven MCN; 12 and 16 patients underwent surgery within and after 6 months from the initial examination (Groups A and B, respectively). Outcome measures included changes in imaging findings until surgery in Group B, pathological findings between both groups and differences in pathological findings between patients with and without regular follow-up imaging in Group B. RESULTS: In Group B, the median cyst size was 30 and 48 mm at the initial examination and immediately before surgery, respectively. The incidence of mural cysts, thickened walls and mural nodules were 25, 19 and 0%, respectively, at the initial examination and 69, 56 and 31%, respectively, immediately before surgery. There were no significant differences in the invasive carcinoma rates between Groups A and B (13 vs. 17%). Regular follow-up imaging was offered to Group B. Among these, invasive carcinoma was found in one patient exhibiting no recurrence. One patient without follow-up imaging had invasive carcinoma recurrence post-operatively. CONCLUSIONS: MCNs increased in size, and typical imaging findings appeared over time. For undiagnosed MCN, regular follow-up examination contributed to the determination of the appropriate surgical timing.

Bile aspiration during EUS-guided hepaticogastrostomy is associated with lower risk of postprocedural adverse events: a retrospective single-center study.

BACKGROUND: In endoscopic retrograde cholangiopancreatography (ERCP), reduction of pressure inside of the bile duct by bile aspiration is a well-known method to lower the rate of adverse events (AEs) including cholangitis. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been introduced as an alternative to ERCP. The use of self-expandable metallic stents is recommended in EUS-HGS to reduce bile leak; however, other methods to reduce the rate of AEs including bile leak, abdominal pain, fever, and sepsis, have not been elucidated yet. This study investigated whether bile aspiration during EUS-HGS decreased the rate of postprocedural AEs. METHODS: Consecutive patients who underwent EUS-HGS between July 2016 and April 2020 were retrospectively evaluated in this study. EUS-HGS was performed at a tertiary cancer center. Patient characteristics, site of biliary obstruction, the quantity of bile aspirated during EUS-HGS, type of stent, whether or not antegrade stenting (AS) was performed, procedure time, and AEs were assessed based on a prospectively recorded institutional endoscopy database. Logistic regression analysis was performed to identify factors affecting postprocedural AEs. RESULTS: Ninety-six patients were included in the study. EUS-guided HGS with and without AS was performed in 45 and 51 patients, respectively. Bile was aspirated in 71 patients (74%). The quantity of bile aspirated was 0-10 mL and > 10 mL in 40 and 56 patients, respectively. AEs including fever, abdominal pain, postprocedural cholangitis, sepsis, acute pancreatitis, and bleeding occurred in 45 patients (47%). The AE rates were 65% (26/40) and 34% (19/56), for 0-10 mL and > 10 mL bile, respectively (p = 0.004). Using multivariate analysis, the only independent factor affecting the occurrence of AEs was found to be an aspirated bile amount of 0-10 mL (odds ratio: 4.16; 95% CI 1.6-10.8). CONCLUSIONS: Bile aspiration of more than 10 mL during EUS-HGS contributes to reducing the rate of postprocedural AEs.

Transrectal laparoscopy using flexible endoscopy with a submucosal tunneling method: Porcine survival model.

OBJECTIVES: Transrectal laparoscopy (TRLS) using a flexible endoscope was recently proposed for peritoneal observation. Although previous studies have reported its feasibility, follow-up durations were insufficient to ascertain technical safety. Moreover, knowledge about the technical feasibility of collecting peritoneal cytological lavage or ascites during TRLS is limited. Thus, this study aimed to confirm the safety and efficacy of TRLS in a porcine survival model. METHODS: After creating artificial ascites in 10 animals, TRLS was performed as follows: submucosal tunnel creation on the anterior wall of the rectum, intentional perforation at the distal end of the tunnel, endoscopic ascites collection and intraperitoneal observation, and clip closure at the mucosal incision site. The pigs were administered antibiotics orally for 7 days after TRLS and killed for histological evaluation and bacterial culture after 28 days of observation. RESULTS: The technical success rates of insertion into the abdominal cavity, ascites collection, and clip closure were 100%. All frequent anatomical sites for peritoneal dissemination including the stomach, subdiaphragmatic space, and pelvic space were fully observable without adverse events. The median procedure time was 36.3 min. Full 28-day survival was observed in all cases without any infection. The autopsies showed no infection, including abscess formation. Bacterial cultures of the peritoneal cavity were negative 28 days after TRLS in all cases. CONCLUSIONS: Transrectal laparoscopy enabled ascites collection and intraperitoneal observation without adverse events. All animals survived without peritonitis. Therefore, TRLS can be an option for intraperitoneal examination.

Gross visual inspection by endosonographers during endoscopic ultrasound-guided fine needle aspiration.

BACKGROUND/OBJECTIVES: A clear criterion for terminating endoscopic ultrasound fine needle aspiration (EUS-FNA) without rapid on-site evaluation (ROSE) has not been established. However, a possible solution includes gross visual inspection (GVI) of the sample obtained with EUS-FNA. We performed a retrospective study to elucidate the efficacy of GVI for the diagnostic yield of EUS-FNA. METHODS: Patients who underwent EUS-FNA of a pancreatic mass using a standard 22-G needle from January 2017 to December 2017 were included in the study. At least two punctures were performed for each patient, and GVI was performed for each pass by endoscopists. The correlation between GVI and pathological findings were investigated per needle pass for the first two passes. Regarding GVI, we evaluated the presence of a visible core (with or without) and the sample quantity (large or small). RESULTS: We evaluated 126 EUS-FNA specimens and analyzed 252 needle passes. A final diagnosis of malignancy was made for 119 patients (94%). Accuracy rates were 92.5% with a visible core and 70.0% without a visible core (p < 0.01), and 85.2% for large sample quantities and 70.2% for small sample quantities (p < 0.01). Univariate analysis indicated that the presence of a visible core and large sample quantity were associated with accuracy. Multivariate analysis indicated that only the presence of a visible core was significant. CONCLUSIONS: GVI can predict the correct diagnosis when ROSE is unavailable. Evaluating the presence of a visible core is more sensitive than assessing the quantity of the sample obtained.

Benefit of high negative pressure during endoscopic ultrasound-guided fine-needle aspiration with standard 22-gauge needles for pancreatic lesions: a retrospective comparative study.

OBJECTIVES: Few studies are available on high negative pressure (HNP) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study compared the diagnostic yield between HNP and normal negative pressure (NNP) during EUS-FNA for solid pancreatic masses. METHODS: Consecutive patients with pancreatic masses who underwent EUS-FNA using a 22-G needle with either HNP or NNP for both the first and second passes were retrospectively examined for diagnostic yield. Rapid on-site evaluation (ROSE) was unavailable at our center. The main outcome measures were the number of passes, diagnostic accuracy and quantity of histological samples. RESULTS: Two hundred patients underwent EUS-FNA (n = 97, HNP; n = 103, NNP) over a 22-month period. A significantly lower median number of passes was required for HNP than for NNP (2 vs. 3; p < .001). There was no significant difference in diagnostic accuracy between the two groups. The rate of obtaining a histological sample larger than a 10× power field in length was significantly higher for HNP than for NNP (76.4% vs. 59.6%; p = .0019). In the multivariate analysis, a large tumor size (>20 mm) and HNP were identified as factors influencing the acquisition of a larger histological sample. CONCLUSIONS: There was no significant difference in diagnostic accuracy between HNP and NNP. HNP required fewer passes without ROSE and was related to the acquisition of a larger histological sample. HNP may be useful when few samples are available for EUS-FNA with NNP or a larger histological sample is needed.

[A case of jejunal neuroendocrine carcinoma complicated with dermatomyositis].

A 65-year-old woman who had been diagnosed with dermatomyositis presented to the hospital with a small bowel mass. She had tested positive for fecal occult blood test and anemia at a medical checkup;therefore, computerized tomography (CT) was performed at the previous hospital and it had revealed thickening of the intestinal wall. Abdominal contrast-enhanced CT, single-balloon assisted enteroscopy, and biopsy led to a diagnosis of poorly differentiated jejunal adenocarcinoma. The patient underwent laparoscopic segmental resection of the jejunum with dissection of mesenteric lymph nodes. A histological examination revealed that the tumor was neuroendocrine carcinoma (NEC), large-cell type of the jejunum, pT3, pN0, sM0, and pStage IIA. Immunohistochemically, the NEC component was positive for chromogranin A and negative for neural cell adhesion molecule and synaptophysin. The MIB-1 index was 60%. Four courses of postoperative chemotherapy using cisplatin and etoposide were administered. The patient is currently doing well without any recurrence or metastasis. To the best of the author's knowledge, this is the first report of dermatomyositis associated with primary jejunal NEC.