IS THERE A ROLE FOR BILIODIGESTIVE BYPASS SURGERY IN TREATING CHOLESTASIS IN ADVANCED PANCREATIC CANCER?

BACKGROUND: The unresectable pancreatic head tumors develop obstructive jaundice and cholestasis during follow-up. Cholestasis is associated with complications and treatment options are endoscopic stenting (ES) and biliary bypass surgery (BBS). AIMS: The aim of the current study was to compare the safety and efficacy of biliary bypass surgery (BBS) and endoscopic stenting (ES) for cholestasis in advanced pancreas cancer. METHODS: This is a retrospective cohort of patients with cholestasis and unresectable or metastatic pancreas cancer, treated with BBS or ES. Short and long-term outcomes were evaluated. We considered the need for hospital readmission due to biliary complications as treatment failure. RESULTS: A total of 93 patients (BBS=43; ES=50) were included in the study. BBS was associated with a higher demand for postoperative intensive care (37 vs.10%; p=0.002, p<0.050), longer intensive care unit stay (1.44 standard deviation±2.47 vs. 0.66±2.24 days; p=0.004, p<0.050), and longer length of hospital stay (7.95±2.99 vs. 4.29±5.50 days; p<0.001, p<0.050). BBS had a higher risk for procedure-related complications (23 vs. 8%; p=0.049, p<0.050). There was no difference in overall survival between BBS and ES (p=0.089, p>0.050). ES was independently associated with a higher risk for treatment failure than BBS on multivariate analysis (hazard ratio 3.97; p=0.009, p<0.050). CONCLUSIONS: BBS is associated with longer efficacy than ES for treating cholestasis in advanced pancreatic cancer. However, the BBS is associated with prolonged intensive care unit and hospital stays and higher demand for intensive care.

Endoscopic ultrasound-guided versus percutaneous liver biopsy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Percutaneous liver biopsy (PC-LB) has long been the usual method for acquisition of liver tissue. Recently, endoscopic ultrasound-guided liver biopsy (EUS-LB) has gained popularity as an alternative modality. We aimed to compare the efficacy and safety of EUS-LB versus PC-LB. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library databases for randomized controlled trials (RCTs) comparing EUS-LB with PC-LB published until October 20, 2023. The primary outcome was diagnostic adequacy. Secondary outcomes were: the number of complete portal tracts (CPTs), longest sample length (LSL), total sample length (TSL), post-procedure pain scores, and adverse events (AEs), including overall AEs and AEs excluding minor post-procedure symptoms. We compared binary outcomes using risk ratios (RRs) and continuous outcomes using the mean difference (MD) or standardized mean difference (SMD), with 95%CIs. RESULTS: Four RCTs (258 patients) were included. The EUS-LB group presented lower post-procedure pain scores (SMD -0.58, 95%CI -0.95 to -0.22) than the PC-LB group. Both groups performed similarly in terms of diagnostic adequacy (RR 1.0, 95%CI 0.96 to 1.04), number of CPTs (MD 2.57, 95%CI -4.09 to 9.22), LSL (MD -2.91 mm, 95%CI -5.86 to 0.03), TSL (MD 4.16 mm, 95%CI -10.12 to 18.45), overall AEs (RR 0.54, 95%CI 0.20 to 1.46), and AEs excluding minor post-procedure symptoms (RR 1.65, 95%CI 0.21 to 13.02). CONCLUSIONS: This meta-analysis suggests that EUS-LB is as safe and effective as PC-LB and is associated with lower post-procedure pain scores.Registration on PROSPERO: CRD42023469469.

The addition of endoscopic sphincterotomy to biliary stent placement and its impact on the risk of adverse events: an updated meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Endoscopic sphincterotomy (ES) is not mandatory before biliary stenting. The impact of ES before biliary stent placement remains uncertain. Previous studies have reported that ES can increase adverse event rates by up to 4.5 times compared with no ES. We aimed to assess the occurrence of post-ERCP adverse events following biliary stent placement with and without ES. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials. The primary outcome was post-ERCP pancreatitis (PEP). Subgroup analyses were performed with patients undergoing biliary drainage due to obstruction, using metal stents, and using plastic stents. Secondary outcomes were postprocedural bleeding, perforation, stent/catheter occlusion, stent/catheter migration, and cholangitis. Heterogeneity was examined with I2 statistics, and a random-effects model was used. Review Manager 5.4 was used for statistical analyses. RESULTS: Seven RCTs with 1022 patients were included. There was no significant difference between the ES and non-ES groups (odds ratio [OR], .46; 95% CI, .19-1.09; P = .08; I2 = 59%) regarding PEP; however, a significant difference in bleeding rates was found between groups, favoring non-ES (OR, 7.01; 95% CI, 2.24-21.99; P = .0008; I2 = 0%). The analysis of the occurrence of cholangitis (OR, 1.25; 95% CI, .58-2.69; P = .56; I2 = 67%), perforation (OR, 1.95; 95% CI, .07-55.73; P = .70; I2 = 58%), stent/catheter migration (OR, 2.15; 95% CI, .61-7.57; P = 0.23; I2 = 6%), and stent/catheter occlusion (OR, .91; 95% CI, .37-2.25; P = .84; I2 = 0%) did not favor either group. CONCLUSIONS: Performing ES before biliary drainage does not affect the PEP rate but is associated with an increased postprocedural bleeding rate.

Machine Learning-Based Prediction of Responsiveness to Neoadjuvant Chemoradiotheapy in Locally Advanced Rectal Cancer Patients from Endomicroscopy.

The protocol for treating locally advanced rectal cancer consists of the application of chemoradiotherapy (neoCRT) followed by surgical intervention. One issue for clinical oncologists is predicting the efficacy of neoCRT in order to adjust the dosage and avoid treatment toxicity in cases when surgery should be conducted promptly. Biomarkers may be used for this purpose along with in vivo cell-level images of the colorectal mucosa obtained by probe-based confocal laser endomicroscopy (pCLE) during colonoscopy. The aim of this article is to report our experience with Motiro, a computational framework that we developed for machine learning (ML) based analysis of pCLE videos for predicting neoCRT response in locally advanced rectal cancer patients. pCLE videos were collected from 47 patients who were diagnosed with locally advanced rectal cancer (T3/T4, or N+). The patients received neoCRT. Response to treatment by all patients was assessed by endoscopy along with biopsy and magnetic resonance imaging (MRI). Thirty-seven patients were classified as non-responsive to neoCRT because they presented a visible macroscopic neoplastic lesion, as confirmed by pCLE examination. Ten remaining patients were considered responsive to neoCRT because they presented lesions as a scar or small ulcer with negative biopsy, at post-treatment follow-up. Motiro was used for batch mode analysis of pCLE videos. It automatically characterized the tumoral region and its surroundings. That enabled classifying a patient as responsive or non-responsive to neoCRT based on pre-neoCRT pCLE videos. Motiro classified patients as responsive or non-responsive to neoCRT with an accuracy of ~ 0.62 when using images of the tumor. When using images of regions surrounding the tumor, it reached an accuracy of ~ 0.70. Feature analysis showed that spatial heterogeneity in fluorescence distribution within regions surrounding the tumor was the main contributor to predicting response to neoCRT. We developed a computational framework to predict response to neoCRT by locally advanced rectal cancer patients based on pCLE images acquired pre-neoCRT. We demonstrate that the analysis of the mucosa of the region surrounding the tumor provides stronger predictive power.

Endoscopic ultrasonography-guided gastroenterostomy versus uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction (DRA-GOO): a multicentre randomised controlled trial.

BACKGROUND: Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is a novel endoscopic method to palliate malignant gastric outlet obstruction. We aimed to assess whether the use of EUS-GE with a double balloon occluder for malignant gastric outlet obstruction could reduce the need for reintervention within 6 months compared with conventional duodenal stenting. METHODS: The was an international, multicentre, randomised, controlled trial conducted at seven sites in Hong Kong, Belgium, Brazil, India, Italy, and Spain. Consecutive patients (aged ≥18 years) with malignant gastric outlet obstruction due to unresectable primary gastroduodenal or pancreatobiliary malignancies, a gastric outlet obstruction score (GOOS) of 0 (indicating an inability in intake food or liquids orally), and an Eastern Cooperative Oncology Group performance status score of 3 or lower were included and randomly allocated (1:1) to receive either EUS-GE or duodenal stenting. The primary outcome was the 6-month reintervention rate, defined as the percentage of patients requiring additional endoscopic intervention due to stent dysfunction (ie, restenosis of the stent due to tumour ingrowth, tumour overgrowth, or food residue; stent migration; or stent fracture) within 6 months, analysed in the intention-to-treat population. Prespecified secondary outcomes were technical success (successful placement of a stent), clinical success (1-point improvement in gastric outlet obstruction score [GOOS] within 3 days), adverse events within 30 days, death within 30 days, duration of stent patency, GOOS at 1 month, and quality-of-life scores. This study is registered with ClinicalTrials.gov (NCT03823690) and is completed. FINDINGS: Between Dec 1, 2020, and Feb 28, 2022, 185 patients were screened and 97 (46 men and 51 women) were recruited and randomly allocated (48 to the EUS-GE group and 49 to the duodenal stent group). Mean age was 69·5 years (SD 12·6) in the EUS-GE group and 64·8 years (13·0) in the duodenal stent group. All randomly allocated patients completed follow-up and were analysed. Reintervention within 6 months was required in two (4%) patients in the EUS-GE group and 14 (29%) in the duodenal stent group [p=0·0020; risk ratio 0·15 [95% CI 0·04-0·61]). Stent patency was longer in the EUS-GE group (median not reached in either group; HR 0·13 [95% CI 0·08-0·22], log-rank p<0·0001). 1-month GOOS was significantly better in the EUS-GE group (mean 2·41 [SD 0·7]) than the duodenal stent group (1·91 [0·9], p=0·012). There were no statistically significant differences between the EUS-GE and duodenal stent groups in death within 30 days (ten [21%] vs six [12%] patients, respectively, p=0·286), technical success, clinical success, or quality-of-life scores at 1 month. Adverse events occurred 11 (23%) patients in the EUS-GE group and 12 (24%) in the duodenal stent group within 30 days (p=1·00); three cases of pneumonia (two in the EUS-GE group and one in the duodenal stent group) were considered to be procedure related. INTERPRETATION: In patients with malignant gastric outlet obstruction, EUS-GE can reduce the frequency of reintervention, improve stent patency, and result in better patient-reported eating habits compared with duodenal stenting, and the procedure should be used preferentially over duodenal stenting when expertise and required devices are available. FUNDING: Research Grants Council (Hong Kong Special Administrative Region, China) and Sociedad Española de Endoscopia Digestiva.

Comparing three-dimensional endorectal ultrasound and magnification chromoendoscopy for early rectal neoplasia invasion depth assessment.

INTRODUCTION: Accurate assessment of invasion depth of early rectal neoplasms is essential for optimal therapy. We aimed to compare three-dimensional endorectal ultrasound (3D-ERUS) with magnification chromoendoscopy (MCE) regarding their accuracy in assessing parietal invasion depth (T). METHODS: Patients with middle and distal rectum neoplasms were prospectively included. Two providers blinded to each other's assessment performed 3D-ERUS and MCE, respectively. The T stage assessed through ERUS was compared to the MCE evaluation. The results were compared to the surgical specimen anatomopathological report. Sensitivity, specificity, accuracy, positive (PPV), and negative (NPV) predictive values were calculated for the T stage and for the final therapy (local excision or radical surgery). RESULTS: In 8 years, 70 patients were enrolled, and all underwent both exams. MCE and ERUS showed an accuracy of 94.3% and 85.7%, sensitivity of 83.7 and 93.3%, specificity of 96.4 and 83.6%, PPV of 86.7 and 60.9%, and NPV of 96.4 and 97.9%, respectively. Kappa for T stage assessed through ERUS was 0.64 and 0.83 for MCE. CONCLUSION: MCE and 3D-ERUS had good diagnostic performance, but the endoscopic method had higher accuracy. Both methods reliably assessed lesion extension, circumferential involvement, and distance from the anal verge.

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC. METHODS: Patients who underwent ESD revealing T1b EC (squamous or adenocarcinoma) at 10 academic tertiary referral centers in the United States (n = 9) and Brazil (n = 1) were included. Demographic and clinical data were abstracted. ESD using either traction techniques (tunneling, pocket) or traction devices (clip line, traction wire) were classified as ESD with traction (Tr-ESD) and those without were classified as conventional ESD without traction. The primary outcome was a negative VM. Multivariable logistic regression was used to assess associations with negative VMs. RESULTS: A total of 166 patients with pathologically staged T1b EC underwent Tr-ESD (n = 63; 38%) or conventional ESD without traction (n = 103; 62%). Baseline factors were comparable between both groups. On multivariable analysis, Tr-ESD was found to be independently associated with negative VMs (odds ratio, 2.25; 95% confidence interval, 1.06-4.91; P = .037) and R0 resection (odds ratio, 2.83; 95% confidence interval, 1.33-6.23; P = .008). CONCLUSION: Tr-ESD seems to be associated with higher odds of negative VMs than ESD without traction for pathologically staged T1b EC, and future well-conducted prospective studies are warranted to establish the findings of the current study.

Underwater versus conventional endoscopic mucosal resection for colorectal lesions: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) is the established method for the resection of non-pedunculated colorectal lesions (NPCRL) ≥ 10 mm. In the last decade, underwater endoscopic mucosal resection (UEMR) has been introduced as a potential alternative. The aim of this systematic review with meta-analysis is to compare the recurrence and safety of UEMR and CEMR by analyzing only randomized controlled trials (RCTs). METHODS: We systematically searched PubMed, Cochrane Library and EMBASE until April 2023. Studies met the following inclusion criteria: (1) RCTs, (2) comparing UEMR with CEMR, (3) NPCRL ≥ 10 mm, and (4) reporting the outcomes of interest. Primary outcomes were recurrence and safety. Secondary outcomes were en bloc, R0, complete resection, clipping and adverse events per type. RESULTS: Five RCTs were included. UEMR was associated with a lower recurrence rate (OR: 0.56; 95% CI: 0.32-0.97). Thus, the RR of recurrence was 1.7 times higher in the CEMR group (95% CI, 1.04-2.77). There was no significant difference in the pooled safety analysis. UEMR showed better en bloc resection rates (OR: 1.54; 95% CI: 1.15-2.07), but subgroup analysis showed comparable rates in lesions ≥ 20 mm. R0 resection was higher in UEMR (OR: 1.72; 95% CI: 1.23-2.41). Other outcomes were not different between the 2 groups. CONCLUSIONS: UEMR is as safe as CEMR, with a higher overall R0 rate and a higher en bloc resection rate for lesions < 20 mm, leading to a lower overall recurrence rate. The results of this meta-analysis support the widespread use of UEMR.

Self-expandable metallic stent-induced esophagorespiratory fistulas in patients with advanced esophageal cancer.

BACKGROUND/AIMS: Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMS-ERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer. METHODS: This retrospective study was performed at the Instituto do Cancer do Estado de São Paulo. All patients with malignant esophageal strictures who underwent esophageal SEMS placement between 2009 and 2019 were included in the study. RESULTS: Of the 335 patients, 37 (11.0%) developed SEMS-ERF, with a median time of 129 days after SEMS placement. Stent flare of 28 mm (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.15-5.51; p=0.02) and post-stent chemotherapy (HR, 2.0; 95% CI, 1.01-4.00; p=0.05) were associated with an increased risk of developing SEMS-ERF, while lower-third tumors were a protective factor (HR, 0.5; 95% CI, 0.26-0.85; p=0.01). No difference was observed in overall survival. CONCLUSION: The incidence of SEMS-ERFs was 11%, with a median time of 129 days after SEMS placement. Post-stent chemotherapy and a 28 mm stent flare were associated with a higher risk of SEMS-ERF.

The Role of Probe-Based Confocal Laser Endomicroscopy (pCLE) in the Diagnosis of Sustained Clinical Complete Response Under Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Adenocarcinoma: a Score Validation.

BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Impact of radiotherapy on adverse events of self-expanding metallic stents in patients with esophageal cancer.

Self-expanding metallic stents (SEMS) are considered the treatment of choice for the palliation of dysphagia and fistulas in inoperable esophageal neoplasms. However, the safety of SEMSs in patients who received or who will be submitted to radiotherapy (RT) is uncertain. The study aimed to evaluate the impact of RT on adverse events (AEs) in patients with esophageal cancer with SEMSs. This is a retrospective study conducted at a tertiary cancer hospital from 2009 to 2018. We collected information regarding RT, the histological type of the tumor, the model of SEMSs and AEs after stent placement. Three hundred twenty-three patients with malignant stenosis or fistula were treated with SEMSs. The predominant histological type was squamous cell carcinoma (79.6%). A total of 282 partially covered and 41 fully covered SEMSs were inserted. Of the 323 patients, 182 did not received RT, 118 received RT before SEMS placement and 23 after. Comparing the group that received RT before stent insertion with the group that did not, the first one presented a higher frequency of severe pain (9/118 7.6% vs. 3/182 1.6%; P = 0.02). The group treated with RT after stent placement had a higher risk of global AEs (13/23 56.5% vs. 63/182 34.6%; P = 0.019), ingrowth/overgrowth (6/23 26.1% vs. 21/182 11.5%; P = 0.045) and gastroesophageal reflux (2/23 8.7% vs. 2/182 1.1%; P = 0.034). Treatment with RT before stent placement in patients with inoperable esophageal neoplasm prolongs survival and is associated with an increased risk of severe chest pain. Treatment with RT of patients with an esophageal stent increases the frequency of minor, not life-threatening AEs.

Results of endoscopic biliary drainage in patients with malignant hilar stricture.

In Malignant Hilar Biliary Stricture (MHBS) palliative biliary drainage is a frequent strategy, improving the quality of life, reducing pruritus, loss of appetite and relieving cholangitis. The endoscopic approach is an effective, although challenging procedure. This study aimed to evaluate technical and clinical success rates of biliary drainage by ERCP. This is a retrospective study including all patients with MHBS referred to Instituto do Cancer do Hospital de São Paulo (ICESP) submitted to biliary drainage by ERCP, between January 2010 and December 2017. Multivariable logistic regression was performed to evaluate predictors of clinical failure, as total bilirubin levels, Bismuth classification, number of hepatic sectors drained and presence of cholangitis. In total, 82 patients presenting unresectable MHBS were included in this study. 58.5% female and 41.5% male, with a mean age of 60±13 years. Bismuth classification grades II, IIIA, IIIB and IV were noted in 23.2%, 15.9%, 14.6% and 46.3%, respectively. Technical and clinical success was achieved in 92.7% and 53.7% respectively. At multivariable logistic-regression analyses, Bismuth IV strictures were related to higher clinical failure rates when compared to other strictures levels, with an Odds Ratio of 5.8 (95% CI 1.28‒20.88). In conclusion, endoscopic biliary drainage for malignant hilar biliary stricture had a high technical success but suboptimal clinical success rate. Proximal strictures (Bismuth IV) were associated with poor drainage outcomes.