Diagnostic yield of endoscopic and EUS-guided biopsy techniques in subepithelial lesions of the upper GI tract:a systematic review

Background and Aims: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract. Methods: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification. Results: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB. Conclusions: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events.</p

Diagnostic yield of endoscopic and EUS-guided biopsy techniques in subepithelial lesions of the upper GI tract:a systematic review

Background and Aims: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract. Methods: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification. Results: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB. Conclusions: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events.</p

Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma

Background: Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort. Methods: Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Results: In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P &lt; 0.001). Discussion: Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers

Preoperative endoscopic biliary drainage by metal versus plastic stents for resectable perihilar cholangiocarcinoma

Background and Aims: Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients. Methods:In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics. Results: A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred significantly less in the SEMSs group (31% vs 64%; P &lt; .001). Besides less cholangitis after SEMSs placement (15% vs 31%; P = .012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P = .71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients. Conclusions: Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar.</p

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.</p

Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Background: One of the cornerstones of palliative treatment for unresectable perihilar cholangiocarcinoma is biliary stent placement in order to restore biliary drainage. In this review, the potential added value of RFA with stent placement in comparison to stent placement alone in patients with unresectable perihilar cholangiocarcinoma is analyzed.  Methods: We performed a comprehensive online search for relevant articles in November 2021 (PROSPERO ID: CRD42021288180). The primary endpoint was difference in overall survival. Secondary endpoints included overall survival, stent patency and complications. Only studies comparing survival after RFA + stent placement with stent placement alone were included in the meta-analysis. Non-comparative studies or comparative studies describing stent patency only were included in the systematic review.  Results: A total of nine studies, including 217 patients with pCCA who underwent RFA + stent placement and 294 patients who underwent stent-only treatment, met the inclusion criteria for the primary endpoint analysis. Direct comparison between the two treatment groups showed a significantly longer overall survival for RFA + stent treatment, with a pooled HR of 0.65 [95% CI, 0.50–0.84, I2 = 38%]. When all eligible studies were included, RFA + stent treatment revealed an overall survival of 9.5 months [95% CI, 6.3–12.6], whereas survival for stent-only treatment was 7.0 months [95% CI, 5.7–8.2]. Due to the heterogeneity of the data, no pooled data analysis could be performed on stent patency or complications.  Conclusions: RFA + stent placement displays promising potential to prolong survival. However, further research incorporating confounding factors like use of palliative chemotherapy is necessary in order to validate these findings

Protein biomarkers in pancreatic juice and serum for identification of pancreatic cancer

Background and Aims: To date, surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) has not lived up to expectations, as identification of curable stages through imaging remains challenging. Biomarkers are therefore needed. Pancreatic juice (PJ) may be a promising source, because it is in direct contact with the ductal epithelial lining from which PDAC arises. We aimed to develop a panel of biomarkers from serum and PJ to detect PDAC for future surveillance purposes. Methods: All patients who underwent PJ collection on secretin stimulation at the Erasmus MC were included. Both PJ and serum were evaluated. Protein levels were determined by the Lowry assay. Potential biomarkers (interleukin-8, interferon-γ, neutrophil gelatinase-associated lipocalin [NGAL], mucin 5, subtype AC [MUC5AC], mucin 2, phospholipase A2 group IB) were selected based on previously reported outcomes and assessed with enzyme-linked immunosorbent assay. Serum carbohydrate antigen 19-9 (CA19-9) values were determined by electrochemiluminescence immunoassay. Results: This study included 59 cases and 126 surveilled control subjects (who underwent PJ collection), of whom 71 had a hereditary predisposition (35 genetic, 36 familial) and 55 had (suspected neoplastic) pancreatic cysts. CA19-9 values were available for 53 cases and 48 control subjects. Serum CA19-9, as well as PJ interleukin-8, NGAL and MUC5AC, were associated with PDAC independent of age, gender, and presence of diabetes mellitus. Serum CA19-9 had a significantly higher area under the curve (AUC; .86; 95% confidence interval [CI], .79-.94) than individual PJ markers (AUC, .62-.70). A combination of PJ markers and serum CA19-9 (panel 2: sensitivity 42% [95% CI, 29-57] and specificity 96% [95% CI, 86-100]) did not improve diagnostic performance compared with CA19-9 alone (sensitivity 70% [95% CI, 56-82] and specificity 85% [95% CI, 72-94]). Conclusions: High levels of serum CA19-9 and PJ-derived proteins are associated with PDAC. Prospective surveillance studies including individuals at risk of developing PDAC are required to validate these findings