Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study.

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

Biliary Drainage in Hilar and Perihilar Cholangiocarcinoma; 25-Year Experience at a Tertiary Cancer Center.

INTRODUCTION: This study analyzes the optimal biliary stenting strategy for palliation in cholangiocarcinoma (CCA). METHODS: This is a retrospective study of patients with CCA who underwent biliary drainage from 1997-2023. A per-patient analysis of percutaneous biliary drainage (PTBD) rates, the median number of ERCPs, overall survival (OS), and a per-procedure analysis of clinical success (CS), stent-specific Adverse Events (AEs), and mean time to reintervention by stent type and laterality (unilateral(u) & bilateral(b)) is presented. RESULTS: A total of 333 patients underwent 1,050 ERCPs; 85% with plastic stents (PS). PTBD was eventually done in 23% of PS patients, 35% of whom had PS removed prior to PTBD. ERCPs with SEMS/uniSEMS use had higher CS (89%/91%) vs PS/uPS (85% both) and PS within SEMS (PS-SEMS)/uPS-SEMS (71%/74%;p=0.013/p=0.054). Compared to PS, SEMS and PS-SEMS were associated with higher stent-specific AEs (OR SEMS 4.85; 3.23-7.27; PS-SEMS 9.99; 5.33-18.71;p<0.001). Straight PS were associated with more stent-specific AEs compared to double-pigtail stents (OR 6.74; 3.95-11.45;p<0.001). More 7 Fr stents were used in cases with balloon dilation (BD, 109 vs. 88 with no BD; p<0.001). BD had 79% CS rate vs 87% without BD (p<0.001). Cases with pus on ERCP and those with BD had a shorter mean time to reintervention. On regression analyses, higher Bismuth class, PS use, and PS-SEMS use were associated with a shorter mean time to repeat ERCP. 52% of patients in the bSEMS arm died from cholangitis (p=0.005). CONCLUSION: The relatively higher clinical success of SEMS is countered by the higher stent-specific complication rate. PS can be removed and may better facilitate PTBD. Within PS types, DPTs may have fewer stent-specific AEs. Cases requiring balloon dilation and with endoscopic evidence of pus may benefit from earlier reintervention.

A decade's experience of managing suspected pancreatic adenocarcinoma at a tertiary cancer center.

Background: We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital. Method: Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016. Results: Among the 309 patients, the median age was 67 years and 56% were men. The most common presenting symptoms were abdominal pain (37%) and jaundice (29%). Concordance between radiographic diagnosis and final pathology was 89%. The mean lesion size was 34.9 mm on computed tomography and 31.5 mm on EUS. There were 197 patients (64%) with localized disease, of whom 115 (58%) had resectable lesions, 61 (31%) had borderline resectable, and 21 (11%) had unresectable lesions (mean CA 19-9 levels 1705 U/mL, 2490 U/mL, and 479 U/mL, respectively). A median of 3 FNA passes were performed to establish a pathologic diagnosis. Two patients (1%) had postprocedural adverse events. Median overall survival was 47 months in those who underwent surgery after EUS and 12 months in those who did not (P<0.001). Conclusions: A multidisciplinary approach is employed for management of suspected pancreatic neoplasm at our tertiary cancer center. A combination of cross-sectional imaging and EUS-FNA serves as a highly effective duo in establishing a tissue diagnosis and staging with a low adverse event rate. Counterintuitively, CA 19-9 is not necessarily higher with resectable lesions than with unresectable lesions, indicating the limitation of CA 19-9 as a pancreatic tumor marker.

Localized Gastroesophageal Adenocarcinoma in the Elderly: Is Age a Factor Associated with Suboptimal Treatment?

INTRODUCTION: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. METHODS: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. RESULTS: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. CONCLUSION: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.

Cryotherapy for removal of an embedded, partially covered esophageal stent.

Video 1Cryotherapy for removal of an embedded, partially covered esophageal stent.

3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).

Increased relative risk of delayed hemorrhage in patients taking anticoagulant/antiplatelet medications with concurrent aspirin therapy: implications for clinical practice based on 3-year retrospective analysis in a large health system.

PURPOSE: The incidence of delayed posttraumatic intracranial hemorrhage (DH) in patients on anticoagulant (AC) and antiplatelet (AP) medications, especially with concurrent aspirin therapy, is not well established, with studies reporting disparate results with between 1-10% risk of DH and 0-3% mortality. The purpose of this 3-year retrospective study is to evaluate the true risk of DH in patients on AP/AC medications with or without concurrent aspirin therapy. METHODS: One thousand forty-six patients taking AP and AC medications presenting to network emergency departments with head trauma who had repeat CT to evaluate for DH were included in the study. Repeat examinations were typically performed within 24 h (average follow-up time was 21 h and 99% were within 3 days). Mean time to DH was 20 h. All positive studies were reviewed by two board-certified neuroradiologists. Patients were excluded from the study if hemorrhage was retrospectively identified on the initial examination. Cases were reclassified as negative if hemorrhage on the follow-up examination was thought to be not present or artifactual. Cases were considered positive if the initial examination was negative and the follow-up examination demonstrated new hemorrhage. RESULTS: Overall, there was 1.91% incidence (20 patients) of DH and 0.3% overall mortality (3 patients). The group of patients taking warfarin or AP agents demonstrated a significantly higher rate of DH (3.2% compared to 0.9%) and higher mortality (0.9% compared to 0.0%) compared to the DOAC group (p < 0.01). The risk of DH in patients taking AC or AP agents with aspirin (13/20 cases) was significantly higher (RR 3.8, p < 0.01) than that of patients taking AC or AP alone (7/20 cases). CONCLUSION: The risk of DH was significantly higher in patients taking aspirin in addition to AC/AP medications. Repeat imaging should be obtained for trauma patients taking AC/AP agents with concurrent aspirin. The rate of DH was also significantly higher in patients taking warfarin or AP agents when compared to patients taking DOACs. Repeat examination should be strongly considered on patients taking warfarin or AP agents without aspirin. Given the relatively low risk of DH in patients taking DOACs alone, repeat imaging could be reserved for patients with external signs of trauma or dangerous mechanism of injury.

Adequacy evaluation and use of pancreatic adenocarcinoma specimens for next-generation sequencing acquired by endoscopic ultrasound-guided FNA and FNB.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition (EUS-TA), especially endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), is the mainstay of tissue acquisition for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using flexible biopsy needles has been used for patients with PDAC in an effort to increase diagnostic yields and biomarker testing. However, the role of EUS-TA in biomarker testing for personalized therapy or precise chemotherapy for PDAC is not well established. METHODS: PDAC cases with specimens acquired through concurrent EUS-FNA and EUS-FNB were identified retrospectively. Smears were prepared from EUS-FNA sampling, and cell blocks (CBs) were prepared from EUS-FNB sampling. Rapid onsite evaluation was conducted for all cases for diagnostic adequacy. The adequacy for biomarker testing, including next-generation sequencing (NGS) and immunohistochemistry (IHC) assays, was evaluated, and cases with smears and CBs adequate for NGS were processed for targeted NGS. RESULTS: There were 26 PDAC cases concurrently sampled by EUS-FNA and EUS-FNB. EUS-FNA smears for all 26 cases and EUS-FNB CBs for 20 cases (77%) were diagnostic for PDAC. Twenty-one smears (81%) and 11 CBs (42%) were adequate for NGS. Nine cases with both smears and CBs adequate for NGS underwent NGS, which identified clinically significant gene mutation variants, including KRAS, TP53, and SMAD4 mutations. CONCLUSIONS: Both EUS-FNA and EUS-FNB can provide optimal material for targeted NGS for PDACs. In PDAC cases subjected to concurrent EUS-FNA and EUS-FNB, EUS-FNA specimens had greater diagnostic yields and more adequate material for NGS than EUS-FNB specimens, whereas EUS-FNB was more suitable for IHC-based biomarker testing.

Salvage Esophagectomy Definition Influences Comparative Outcomes in Esophageal Squamous Cell Cancers.

BACKGROUND: In retrospective studies the definition of salvage esophagectomy has been inconsistent and is a source of bias. We sought to describe how variability in the definition of salvage affects comparative outcomes of trimodality therapy (TMT) and bimodality therapy (BMT). METHODS: Patients with locally advanced esophageal squamous cell carcinoma who completed chemoradiation therapy (CRT) from 2002 to 2017 were identified. TMT included patients who had a planned esophagectomy after CRT. BMT included patients treated with CRT only plus salvage esophagectomy, variably defined as an esophagectomy occurring (A) 3 months after CRT; (B) 3 months after CRT, excluding delayed recovery; (C) 3 months after CRT, excluding delayed workup; or (D) 6 months after CRT. Long-term survival outcomes between the TMT and BMT groups were compared for each definition of salvage esophagectomy. Time to surgery was included a priori in a multivariable model for overall survival. RESULTS: Of 143 patients, 90 (63%) underwent esophagectomy and 53 (37%) received CRT only. Although the total patients remained the same, the composition of the TMT and BMT groups varied by salvage definitions A through D. Various definitions resulted in different 5-year survival rates for TMT vs BMT groups: (A) 56% vs 39%, (B) 61% vs 34%, (C) 50% vs 42%, and (D) 51% vs 39%. In a Cox multivariable analysis age and proximal/middle esophageal tumors were associated with worse postoperative survival, but time to surgery was not. CONCLUSIONS: Slight variations in the definition of salvage esophagectomy can influence the interpretation of TMT and BMT outcomes. Future studies should consistently define treatment groups.

How much progress have we made?: a 20-year experience regarding esophageal stents for the palliation of malignant dysphagia.

Esophageal stents are widely used for the palliation of malignant esophageal obstruction. Advances in technology have made esophageal stenting technically feasible and widespread for such obstruction, but complications remain frequent. We present outcomes of a large cohort undergoing esophageal stent placement for malignant esophageal obstruction at a tertiary care cancer center. Patients who underwent placement of esophageal stents for malignancy-related esophageal obstruction between 1 January 2001 and 31 July 2020 were identified. Exclusion criteria included stents placed for benign stricture, fistulae, obstruction of proximal esophagus (proximal to 24 cm from incisors), or post-surgical indications. Patient charts were reviewed for demographics, procedure and stent characteristics, complications, and follow-up. A total of 242 patients underwent stent placement (median age: 64 years, 79.8% male). The majority, 204 (84.3%), had esophageal cancer. During the last two decades, there has been an increasing trend in the number of esophageal stents placed. Though plastic stents were previously used, these are no longer utilized. Complications are frequent and include early complications of pain in 68 (28.1%) and migration in 21 (8.7%) and delayed complications of recurrent symptoms of dysphagia in 46 (19.0%) and migration in 26 (10.7%). Over the study period, there has not been a significant improvement in the rate of complications. During follow-up, 92 (38%) patients required other enteral nutrition modalities after esophageal stent placement. No patient, treatment, or stent characteristics were significantly associated with stent complication or outcome. Esophageal stent placement is an increasingly popular method for palliation of malignant dysphagia. However, complications, particularly pain, migration, and recurrent symptoms of dysphagia are common. Almost 40% of patients may also require other methods of enteral access after esophageal stent placement. Given the high complication rates and suboptimal outcomes, removable stents should be considered as first-line in the case of poor palliative response.

Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies.

PURPOSE: Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. With molecular subtypes of PDAC gaining relevance in the context of therapeutic stratification, the ability to characterize heterogeneity of cancer-specific gene expression patterns is of great interest. In addition, understanding patterns of immune evasion within PDAC is of importance as novel immunotherapeutic strategies are developed. EXPERIMENTAL DESIGN: Single-cell RNA sequencing (scRNA-seq) is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. RESULTS: Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. CONCLUSIONS: Our analysis demonstrates that the use of de novo biopsies from patients with PDAC paired with scRNA-seq may facilitate therapeutic prediction from limited biopsy samples.

Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.

OBJECTIVE: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. METHODS: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation. RESULTS: Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity. CONCLUSIONS: Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.

Integrated genomic profiling and modelling for risk stratification in patients with advanced oesophagogastric adenocarcinoma.

OBJECTIVE: Prognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes. DESIGN: We profiled 40 untreated mEGACs (20 shorter survivors <13 months and 20 longer survivors >36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts. RESULTS: KMT2C alterations were exclusively observed in shorter survivors together with high level of intratumour heterogeneity and complex clonal architectures, whereas the APOBEC mutational signatures were significantly enriched in longer survivors. Notably, the loss of heterozygosity in chromosome 4 (Chr4) was associated with shorter survival and 'cold' immune phenotype characterised by decreased B, CD8, natural killer cells and interferon-gamma responses. Unsupervised transcriptomic clustering revealed a shorter survivor subtype with distinct expression features (eg, upregulated druggable targets JAK2, MAP3K13 and MECOM). An integrated model was then built based on clinical variables and the identified molecular determinants, which significantly segregated shorter and longer survivors. All the above features and the integrated model have been validated independently in multiple TCGA cohorts. CONCLUSION: This study discovered novel molecular features prognosticating overall survival in patients with mEGAC and identified potential novel targets in shorter survivors.

Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples.

PURPOSE: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. EXPERIMENTAL DESIGN: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. RESULTS: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. CONCLUSIONS: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.

Efficacy of uncovered colonic stents for extrinsic versus intrinsic malignant large bowel obstruction.

BACKGROUND: Previous studies evaluating self-expandable metal stents (SEMS) for management of malignant extrinsic colon obstruction have yielded conflicting results. We evaluated the efficacy of uncovered SEMS for extrinsic colon malignancy (ECM) versus intrinsic colon malignancy (ICM). METHODS: Retrospective review of all patients referred for colonic SEMS at a tertiary cancer center between 2007 and 2018 was performed. Primary outcome measures were technical success, clinical success, intervention rate, and overall survival. RESULTS: 138 patients with ECM and 119 patients with ICM underwent attempted stent placement. The rectum and/or sigmoid colon was the most common stricture site. Technical success was lower in the ECM group [86% vs 96% (p = .009)]. Clinical success was lower in the ECM group both at 7 days [82% vs 95% (p = .004)] and at 90 days [60% vs 86% (p < .001)]. Subsequent intervention was required more frequently [44% vs 35%; p = .23] and earlier [median 9 vs 132 days; p < .001] in the ECM group. Median overall survival in the ECM group was 92 vs 167 days. Among predictive variables analyzed, the ECM group had a higher frequency of peritoneal metastasis (87% vs 32%; p < .001), multifocal strictures with requirement for multiple stents (20% vs 6%; p = .002), sharp angulated strictures (39% vs 25%; p = .04) , and radiation therapy (21% vs 10%; p = .02). CONCLUSIONS: Colonic SEMS for ECM is associated with lower technical and clinical success with earlier intervention rates compared with ICM. Our findings can be used to better inform patients and referring providers as well as guide new stent design to enhance efficacy in this population.

Frequency and Implications of Paratracheal Lymph Node Metastases in Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the frequency of paratracheal lymph nodes (LN) metastases and their prognostic influence. SUMMARY BACKGROUND DATA: Paratracheal LNs are considered regional nodes in the esophageal cancer classification, but their metastatic rate and influence on survival remain unclear. METHODS: One thousand one hundred ninety-nine patients with resectable esophageal or gastroesophageal junction adenocarcinoma (EAC) (January 2002 and December 2016) in our Gastrointestinal Medical Oncology Database were analyzed. Paratracheal LNs were defined as1R, 1L, 2R, 2L, 4R, and 4L, according to the 8th American Joint Committee on Cancer classification. RESULTS: Of 1199 patients, 73 (6.1%) had positive paratracheal LNs at diagnosis. The median overall survival (OS) of 73 patients with initial paratracheal LN involvement was 2.10 years (range 0.01-10.1, 5-yrs OS 24.2%). Of 1071 patients who were eligible for recurrence evaluation, 70 patients (6.5%) developed paratracheal LN metastases as the first recurrence. The median time to recurrence was 1.28 years (range 0.28-5.96 yrs) and the median OS following recurrence was only 0.95 year (range 0.03-7.88). OS in 35 patients who had only paratracheal LN recurrence was significantly longer than in patients who had other recurrences (median OS 2.26 vs 0.51 yrs, 5-yrs OS; 26.8% vs 0%, P < 0.0001). Higher T stage (T3/T4) was an independently risk factor for paratracheal LN recurrence (odds ratio 5.10, 95% confidence interval 1.46-17.89). We segregated patients in 3 groups based on the distance of tumor's proximal edge to esophagogastric junction (low; ≤2 cm, medium; 2.0-7.0 cm, and high; >7.0 cm). Paratracheal LN metastases were more frequent with the proximal tumors (low, 4.2%; medium, 12.0%; high, 30.3%; Cochran-Armitage Trend test, P < 0.001). CONCLUSION: Paratracheal LN metastases were associated with a shorter survival in resectable EAC patients. Alternate approaches to prolong survival of this group of patients are warranted.

Safety of the LMA®Gastro™ for Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) patients typically receive either tubeless anesthesia or general endotracheal anesthesia (GETA). Patients receiving propofol-based total intravenous anesthesia (TIVA) are at higher risk of sedation-related adverse events (SRAEs) than patients receiving GETA, primarily due to the need for additional airway maneuvers. The increasing use of non-operating room (OR) anesthesia and the perception of a higher incidence of adverse outcomes in non-OR areas has led to the development of devices to improve safety while maintaining efficiency. The purpose of this study was to evaluate if the LMA Gastro™ could be used as a safe alternative to tubeless anesthesia for successfully completing ERCPs. METHODS: Eligible subjects were identified within the patient population at MD Anderson Cancer Center. Inclusion criteria consisted of adult patients (≥18 years old) scheduled for elective ERCP with TIVA. This was a prospective observational study in which the following data were collected: number of attempts and time to successful supraglottic airway (SGA) placement, vital signs, peripheral oxygen saturation (SpO2), median end-tidal CO2, practitioner satisfaction, and any complications. RESULTS: A total of 30 patients were included in this study. The overall rate of successful SGA placement within 3 attempts was 96.7% (95% confidence interval [CI], 82.8-99.9) or 29/30. The rate of successful ERCP with SGA placement within 3 attempts was 93.3% (95% CI, 77.9-99.2) or 28/30. Both the gastroenterologist and anesthesiologist reported satisfaction with the device in 90% of the cases (in 66.7% of the cases both anesthesiologist and gastroenterologist scored the device a 7/7 for satisfaction). Patients maintained an SpO2 of 95%-100% from induction to discharge, with the exception of 1 patient who had an SpO2 of 93%. The median end-tidal CO2 during the procedure for all patients was 35 mm Hg. Observed aspiration did not occur in any patient. Symptoms of hoarseness (13.3%), mouth soreness (6.7%), sore throat (6.6%), and minor bleeding/cuts/redness/change in taste to the tongue (3.3%) were determined through patient questioning before postanesthesia care unit (PACU) discharge. CONCLUSIONS: Our study suggests that the LMA Gastro might be a safe alternative for ERCP procedures. There was a high level of practitioner satisfaction. Only minor complications, such as hoarseness, mouth or throat soreness, or minor trauma to the tongue were experienced by patients. Similar incidences of complications may occur with GETA and tubeless anesthesia. The procedure was well tolerated by all patients; all patients maintained adequate oxygenation and required only minimal blood pressure support.