Impact of the Early COVID-19 Pandemic on Incidence and Outcomes of Hepatocellular Carcinoma in the United States.

OBJECTIVES: Access to hepatocellular carcinoma (HCC) surveillance and treatments were disrupted during the COVID-19 pandemic. We aimed to characterize the impact of the pandemic on HCC incidence and mortality rates, treatment and outcomes in the U.S. METHODS: Two nationwide databases, the United States Cancer Statistics and the National Vital Statistics System, were used to investigate HCC incidence and mortality between 2001-2020. Trends in age-adjusted incidence (aIR) and mortality (aMR) rates were assessed using joinpoint analysis. The 2020 aIR and aMR were projected based on the pre-pandemic data and compared to actual values to assess the extent of underdiagnosis. We assessed differences in HCC characteristics, treatment and overall survival (OS) between 2020 and 2018-2019. RESULTS: The aIR of HCC in 2020 was significantly reduced compared to 2019 (5.22 vs 6.03/100K PY), representing a 12.2% decrease compared to the predicted aIR in 2020 (5.94/100K PY). The greatest extent of underdiagnosis was observed in Black (-14.87%) and Hispanic (-14.51%) individuals and those with localized HCC (-15.12%). Individuals staged as regional or distant HCC were also less likely to receive treatment in 2020. However, there was no significant difference in short-term OS in 2020 compared to 2018-2019, with HCC mortality rates remaining stable (aMR: 2.76 vs 2.73/100K PY in 2020 vs 2019). CONCLUSIONS: The COVID-19 pandemic resulted in underdiagnosis of HCC, particularly early-stage disease and racial ethnic minorities, and underuse of HCC-directed treatment. Longer follow-up is needed to determine the impact of the COVID-19 pandemic on HCC-related mortality.

Esophageal Self-Expandable Metal Stents Can Fracture in the Distal Third When Used for Post-Bariatric Surgery Complications: A Single Center Experience and Review of the Literature with Video.

Background: Esophageal self-expandable metal stents (SEMS) are an important endoscopic tool. These stents have now been adapted successfully to manage post-bariatric surgery complications such as anastomotic leaks and strictures. In centers of expertise, this has become the primary standard-of-care treatment given its minimally invasive nature, and that it results in early oral feeding, decreased hospitalization, and overall favorable outcomes. Self-expandable metal stents (SEMS) fractures are a rare complication of unknown etiology. We aimed to investigate possible causes of SEMS fractures and highlight a unique endoscopic approach utilized to manage a fractured and impaled SEMS. Methods: This is a retrospective study of consecutive patients who underwent esophageal SEMS placement between 2015-2021 at a tertiary referral center to identify fractured SEMS. Patient demographics, stent characteristics, and possible etiologies of fractured SEMS were identified. A comprehensive literature review was also conducted to evaluate all prior cases of fractured SEMS and to hypothesize fracture theories. Results: There were seven fractured esophageal SEMS, of which six were used to manage post-bariatric surgery complications. Five SEMS were deployed with their distal ends in the gastric antrum and proximal ends in the distal esophagus. All stents fractured within 9 weeks of deployment. Most stents (5/7) were at least 10 cm in length with fractures commonly occurring in the distal third of the stents (6/7). The wires of a fractured SEMS were embedded within the esophagogastric junction in one case, prompting the use of an overtube that was synchronously advanced while steadily extracting the stent. Discussion: We suggest the following four etiologies of SEMS fractures: anatomical, physiological, mechanical, and chemical. Stent curvature at the stomach incisura can lead to strain- and stress-related fatigue due to mechanical bending with exacerbation from respiratory movements. Physiologic factors (gastric body contractions) can result in repetitive squeezing of the stent, adding to metal fatigue. Intrinsic properties (long length and low axial force) may be contributing factors. Lastly, the stomach acidic environment may cause nitinol-induced chemical weakness. Despite the aforementioned theories, SEMS fracture etiology remains unclear. Until more data become available, it may be advisable to remove these stents within 6 weeks.

Sphincterotomy for Biliary Sphincter of Oddi Disorder and idiopathic Acute Recurrent Pancreatitis: THE RESPOND LONGITUDINAL COHORT.

Objective: Sphincter of Oddi Disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurization at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD. Design: Prospective cohort conducted at 14 U.S. centers with 12 months follow-up. Patients undergoing first-time ERCP with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP. The primary outcome was defined as the composite of improvement by Patient Global Impression of Change (PGIC), no new or increased opioids, and no repeat intervention. Missing data were addressed by hierarchal, multiple imputation scheme. Results: Of 316 screened, 213 were enrolled with 190 (89.2%) of these having a dilated bile duct, abnormal labs, iAP, or some combination. By imputation, an average of 122/213 (57.4% [95%CI 50.4-64.4]) improved; response rate was similar for those with complete follow-up (99/161, 61.5%, [54.0-69.0]); of these, 118 (73.3%) improved by PGIC alone. Duct size, elevated labs, and patient characteristics were not associated with response. AP occurred in 37/213 (17.4%) at a median of 6 months post-ERCP and was more likely in those with a history of AP (30.9 vs. 2.9%, p<0.0001). Conclusion: Nearly 60% of patients undergoing ERCP for suspected SOD improve, although the contribution of a placebo response is unknown. Contrary to prevailing belief, duct size and labs are poor response predictors. AP recurrence was common and like observations from prior non-intervention cohorts, suggesting no benefit of sphincterotomy in mitigating future AP episodes.Key Messages: WHAT IS ALREADY KNOWN ON THIS TOPIC: It is not clear if the sphincter of Oddi can cause abdominal pain (Functional Biliary Sphincter of Oddi Disorder) and idiopathic acute pancreatitis (Functional Pancreatic Sphincter of Oddi Disorder), and whether ERCP with sphincterotomy can ameliorate abdominal pain or pancreatitis.WHAT THIS STUDY ADDS: Using multiple patient-reported outcome measures, most patients with suspected sphincter of Oddi disorder improve after ERCP with sphincterotomy.Duct size, elevated pancreatobiliary labs, and baseline patient characteristics are not independently associated with response.There is a high rate of recurrent acute pancreatitis within 12 months of sphincterotomy in those with a history of idiopathic acute pancreatitis.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY: Since a discrete population with a high (> 80-90%) response rate to sphincterotomy for suspected pancreatobiliary pain could not be identified, there is a need for additional observational and interventional studies that include phenotyping of patients using novel imaging or biochemical biomarkers.There remains a pressing need for quantitative nociceptive biomarkers to distinguish pancreatobiliary pain from other causes of abdominal pain or central sensitization.Discovery of blood-, bile-, or imaging-based biomarkers for occult microlithiasis and pancreatitis may be helpful in predicting who is likely to benefit from sphincterotomy.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

5-Hydroxymethylcytosine (5-hmC) loss is a marker of malignancy in biliary neoplasms.

OBJECTIVES: Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies. METHODS: We evaluated 93 cases-20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas-for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls. RESULTS: Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P > .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases. CONCLUSIONS: Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics.

Cancer-related cells and oncosomes in the liquid biopsy of pancreatic cancer patients undergoing surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 10% due to its late diagnosis, rapid metastasis, and chemotherapeutic resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival but the effect of surgery on disease dissemination is unknown. The primary objective of this study was to characterize cellular and acellular blood-based analytes in portal and peripheral blood before pancreatic manipulation, during tumor dissection and immediately after surgical resection to determine the effects of the surgery. This study used the non-enriching third generation High-Definition Single Cell Assay (HDSCA3.0) workflow to investigate heterogeneous circulating rare cell population in the blood. Blood from both sites taken before surgical manipulation of the pancreas had significantly greater incidence of total rare cellular and acellular analytes than normal donor samples. Post-surgery portal and peripheral blood had significantly greater incidence of specific cellular and acellular subtypes compared to the matched pre- and during-surgery samples. Our results reveal that in patients with PDAC liquid biopsy analytes are increased in both the portal and peripheral blood; portal blood contains a higher frequency of analytes than in the peripheral blood; total analytes in the portal and peripheral blood samples were significantly associated with the tumor volume and pathological T stage; and the surgical procedure increased the blood levels of circulating cellular and acellular analytes, but not Epi.CTCs or Mes.CTCs. This study demonstrates liquid biopsy's utility in monitoring patients with PDAC with surgically resectable disease.

EUS-guided coil injection therapy in the management of gastric varices: the first U.S. multicenter experience (with video).

BACKGROUND AND AIMS: Despite the significant morbidity associated with gastric variceal bleeding, there is a paucity of high-quality data regarding optimal management. EUS-guided coil injection therapy (EUS-COIL) has recently emerged as a promising endoscopic modality for the treatment of gastric varices (GV), particularly compared with traditional direct endoscopic glue injection. Although there are data on the feasibility and safety of EUS-COIL in the management of GV, these have been limited to select centers with particular expertise. The aim of this study was to report the first U.S. multicenter experience of EUS-COIL for the management of GV. METHODS: This retrospective analysis included patients with bleeding GV or GV at risk of bleeding who underwent EUS-COIL at 10 U.S. tertiary care centers between 2018 and 2022. Baseline patient and procedure-related information was obtained. EUS-COIL entailed the injection of .018 inch or .035 inch hemostatic coils using a 22-gauge or 19-gauge FNA needle. Primary outcomes were technical success (defined as successful deployment of coil into varix under EUS guidance with diminution of Doppler flow), clinical success (defined as cessation of bleeding if present and/or absence of bleeding at 30 days' postintervention), and intraprocedural and postprocedural adverse events. RESULTS: A total of 106 patients were included (mean age 60.4 ± 12.8 years; 41.5% female). The most common etiology of GV was cirrhosis (71.7%), with alcohol being the most common cause (43.4%). Overall, 71.7% presented with acute GV bleeding requiring intensive care unit stay and/or blood transfusion. The most common GV encountered were isolated GV type 1 (60.4%). A mean of 3.8 ± 3 coils were injected with a total mean length of 44.7 ± 46.1 cm. Adjunctive glue or absorbable gelatin sponge was injected in 82% of patients. Technical success and clinical success were 100% and 88.7%, respectively. Intraprocedural adverse events (pulmonary embolism and GV bleeding from FNA needle access) occurred in 2 patients (1.8%), and postprocedural adverse events occurred in 5 (4.7%), of which 3 were mild. Recurrent bleeding was observed in 15 patients (14.1%) at a mean of 32 days. Eighty percent of patients with recurrent bleeding were successfully re-treated with repeat EUS-COIL. No significant differences were observed in outcomes between high-volume (>15 cases) and low-volume (<7 cases) centers. CONCLUSIONS: This U.S. multicenter experience on EUS-COIL for GV confirms high technical and clinical success with low adverse events. No significant differences were seen between high- and low-volume centers. Repeat EUS-COIL seems to be an effective rescue option for patients with recurrent bleeding GV. Further prospective studies should compare this modality versus other interventions commonly used for GV.

Retrospective quantification of clinical abdominal DCE-MRI using pharmacokinetics-informed deep learning: a proof-of-concept study.

Introduction: Dynamic contrast-enhanced (DCE) MRI has important clinical value for early detection, accurate staging, and therapeutic monitoring of cancers. However, conventional multi-phasic abdominal DCE-MRI has limited temporal resolution and provides qualitative or semi-quantitative assessments of tissue vascularity. In this study, the feasibility of retrospectively quantifying multi-phasic abdominal DCE-MRI by using pharmacokinetics-informed deep learning to improve temporal resolution was investigated. Method: Forty-five subjects consisting of healthy controls, pancreatic ductal adenocarcinoma (PDAC), and chronic pancreatitis (CP) were imaged with a 2-s temporal-resolution quantitative DCE sequence, from which 30-s temporal-resolution multi-phasic DCE-MRI was synthesized based on clinical protocol. A pharmacokinetics-informed neural network was trained to improve the temporal resolution of the multi-phasic DCE before the quantification of pharmacokinetic parameters. Through ten-fold cross-validation, the agreement between pharmacokinetic parameters estimated from synthesized multi-phasic DCE after deep learning inference was assessed against reference parameters from the corresponding quantitative DCE-MRI images. The ability of the deep learning estimated parameters to differentiate abnormal from normal tissues was assessed as well. Results: The pharmacokinetic parameters estimated after deep learning have a high level of agreement with the reference values. In the cross-validation, all three pharmacokinetic parameters (transfer constant Ktrans, fractional extravascular extracellular volume ve, and rate constant kep) achieved intraclass correlation coefficient and R2 between 0.84-0.94, and low coefficients of variation (10.1%, 12.3%, and 5.6%, respectively) relative to the reference values. Significant differences were found between healthy pancreas, PDAC tumor and non-tumor, and CP pancreas. Discussion: Retrospective quantification (RoQ) of clinical multi-phasic DCE-MRI is possible by deep learning. This technique has the potential to derive quantitative pharmacokinetic parameters from clinical multi-phasic DCE data for a more objective and precise assessment of cancer.

Endoscopic Ultrasound Guided Shear Wave Elastography Is Safe With High Feasibility and Reproducibility When Used in the Pancreas: Findings From a Prospective Cohort.

OBJECTIVES: The aim of this study was to assess the safety, feasibility, and reproducibility of endoscopic ultrasound shear wave elastography (EUS-SWE) in the pancreas. METHODS: This is a prospective registry of consecutive patients undergoing clinically indicated EUS. Ten readings of SWE velocities (Vs [distance/time, m/s]) were obtained in the head (HOP), body, and tail of pancreas to quantify tissue stiffness. Each Vs score was accompanied by a reliability measurement VsN (%) with VsN >50% considered reliable. Safety was evaluated by perioperative complications rate. Feasibility was determined by technical success of obtaining measurements. Reproducibility was evaluated using intraclass correlation coefficient analysis. RESULTS: Total of 3320 EUS-SWE measurements were performed on 117 patients without perioperative complications. Measurement success rate was 100% across all locations. Reliable measurements were more common in the HOP (953/1120 [85.1%]) followed by body (853/1130 [75.5%]) and tail of pancreas (687/1070 [64.2%]) (P < 0.001). The analysis showed good reproducibility in all locations (intraclass correlation coefficient range, 0.80-0.89). CONCLUSIONS: Endoscopic ultrasound-SWE is safe, has 100% technical success rate, and is highly reproducible when used in the pancreas. Our study suggests that SWE measurements in the HOP offer the highest reliability, likely because of large study area and less respiratory artifact.

Rising Incidence of Non-Cardia Gastric Cancer among Young Women in the United States, 2000-2018: A Time-Trend Analysis Using the USCS Database.

INTRODUCTION: Although the global incidence of non-cardia gastric cancer (NCGC) is decreasing, there are limited data on sex-specific incidence in the United States. This study aimed to investigate time trends of NCGC from the SEER database to externally validate findings in a SEER-independent national database, and to further assess trends among subpopulations. METHODS: Age-adjusted incidence rates of NCGC were obtained from the SEER database from 2000 to 2018. We used joinpoint models to calculate average annual percentage change (AAPC) to determine sex-specific trends among older (≥55 years) and younger adults (15-54 years). Using the same methodology, findings were then externally validated using SEER-independent data from the National Program of Cancer Registries (NPCR). Stratified analyses by race, histopathology, and staging at diagnosis were also conducted in younger adults. RESULTS: Overall, there were 169,828 diagnoses of NCGC from both independent databases during the period 2000-2018. In SEER, among those <55 years, incidence increased at a higher rate in women (AAPC = 3.22%, p < 0.01) than men (AAPC = 1.51%, p = 0.03), with non-parallel trends (p = 0.02), while a decreasing trend was seen in both men (AAPC = -2.16%, p < 0.01) and women (AAPC = -1.37%, p < 0.01) of the ≥55 years group. Validation analysis of the SEER-independent NPCR database from 2001 to 2018 showed similar findings. Further stratified analyses showed that incidence is disproportionately increasing in young non-Hispanic White women [AAPC = 2.28%, p < 0.01] while remaining stable in their counterpart men [AAPC = 0.58%, p = 0.24] with non-parallel trends (p = 0.04). This pattern was not observed in other race groups. CONCLUSION: NCGC incidence has been increasing at a greater rate in younger women compared to counterpart men. This disproportionate increase was mainly seen in young non-Hispanic White women. Future studies should investigate the etiologies of these trends.

Increasing Pancreatic Cancer Incidence in Young Women in the United States: A Population-Based Time-Trend Analysis, 2001-2018.

BACKGROUND & AIMS: Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data. METHODS: PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults. RESULTS: A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001). CONCLUSION: Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.

Pancreatic Cancer Incidence Trends by Race, Ethnicity, Age and Sex in the United States: A Population-Based Study, 2000-2018.

BACKGROUND AND AIMS: Pancreatic cancer (PC) incidence is increasing at a greater rate in young women compared to young men. We performed a race- and ethnicity-specific evaluation of incidence trends in subgroups stratified by age and sex to investigate the association of race and ethnicity with these trends. METHODS: Age-adjusted PC incidence rates (IR) from the years 2000 to 2018 were obtained from the SEER 21 database. Non-Hispanic White (White), Non-Hispanic Black (Black) and Hispanic patients were included. Age categories included older (ages ≥ 55) and younger (ages < 55) adults. Time-trends were described as annual percentage change (APC) and average APC (AAPC). RESULTS: Younger White [AAPC difference = 0.73, p = 0.01)], Black [AAPC difference = 1.96, p = 0.01)] and Hispanic [AAPC difference = 1.55, p = 0.011)] women experienced a greater rate of increase in IR compared to their counterpart men. Younger Hispanic women experienced a greater rate of increase in IR compared to younger Black women [AAPC difference = -1.28, p = 0.028)] and younger White women [AAPC difference = -1.35, p = 0.011)]. CONCLUSION: Younger women of all races and ethnicities experienced a greater rate of increase in PC IR compared to their counterpart men; however, younger Hispanic and Black women experienced a disproportionately greater increase. Hispanic women experienced a greater rate of increase in IR compared to younger Black and White women.

US Nationwide Insight Into All-cause 30-day Readmissions following Inpatient Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with a high risk for morbidity, mortality, and hospital readmission. Data regarding those risks in the United States is scarce. We assessed post-ERCP 30-day readmission rates, their etiologies, and impact on the health care system using national data. METHODS: Using the National Readmission Database 2016, we identified patients who underwent inpatient ERCP from January 2016 to December 2016 using ICD-10-CM procedure codes. The primary endpoint was all-cause 30-day readmission rate. Etiologies of readmission were identified by tallying primary diagnosis. Multivariable logistic regression with complex survey design was used to identify independent risk factors associated with readmission. RESULTS: A total of 130,145 patients underwent ERCP, 16,278 (12.5%) were readmitted within 30 days, with an associated cost of 268 million dollars. Nearly 40% of readmissions occurred within 7 days, and 47.9% were related to gastrointestinal etiologies. Male gender, increased comorbidities, cirrhosis, Medicare insurance, and pancreatitis or pancreatitis-related indications for ERCP were readmission risk factors. Performance of cholecystectomy on index hospitalization decreased odds of readmission by 50% (adjusted odds ratio: 0.48, 95% confidence interval: 0.45-0.52, P <0.0001). While academic and nonacademic centers had similar readmission rates, high ERCP volume centers had higher rates compared with low-volume centers (adjusted odds ratio:1.10, P =0.008). CONCLUSION: All-cause 30-day readmission rates after inpatient ERCPs are high, mostly occur shortly postdischarge, and impose a heavy health care system burden. Large, multicenter prospective studies assessing the impact of center procedure volume on complications and readmission rates are needed.

Early Application of Next-Generation Sequencing Identifies Pancreatic Mass as Metastasis From an EGFR-Mutated Lung Adenocarcinoma.

Pancreatic metastasis of primary lung adenocarcinoma is a rare occurrence, accounting for <0.3% of all pancreatic malignancies. Given that the prognosis and treatment options for primary pancreatic cancer differ greatly from pancreatic metastases from a primary site, an accurate diagnosis is critical. This report presents a unique case of a 65-year-old man who was admitted with significant unintentional weight loss, fatigue, abdominal pain, and jaundice, and found to have a pancreatic mass initially thought to be primary pancreatic adenocarcinoma and subsequently diagnosed as an EGFR-mutated lung adenocarcinoma with metastases to the pancreas via early application of next-generation sequencing (NGS). The use of NGS early in the patient's clinical course not only changed the treatment strategy but also drastically altered the prognosis. Although metastatic pancreatic adenocarcinoma has a poor prognosis and survival rate, treatment of EGFR-mutated non-small cell lung cancer with EGFR tyrosine kinase inhibitors is associated with high response rates. Importantly, our case demonstrates that timely application of NGS very early in the disease course is paramount to the diagnosis, management, and prognosis of solid malignancies.

Quality improvement project on the development of a management algorithm for iatrogenic perforations and the long-term impact on physician knowledge.

Background and study aims Acute iatrogenic endoscopic perforations (AIEPs) can have high morbidity and mortality, especially colonic perforations. Knowledge of diagnosis and AIEP management can improve patient care. The aims of this study were to: develop an evidence-based AIEP management algorithm; study its short-term and long-term impact on physician knowledge; and evaluate physician knowledge using hypothetical clinical scenarios. Methods An institutional AIEP management algorithm was created using the most current recommendations from the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy. Input from advanced endoscopists, nurses, and anesthesiologists was also obtained. We assessed change in physician knowledge using a 10-item questionnaire before (pretest), a standardized one-page AIEP educational material and algorithm immediately after (post-test) to test short-term retention, and 6 months later (6-month reassessment) to test long-term retention. With the 6-month reassessment, two clinical scenarios based on real AIEP were presented to evaluate application of knowledge. Results Twenty-eight subjects (8 gastroenterology fellows and 20 practicing gastroenterologists) participated in the assessments. Pretest and immediate post-test accuracies were 75 % and 95 % ( P  < 0.01), respectively. Six-month reassessment accuracies were 83.6 %, significantly worse compared to post-test accuracies ( P  < 0.05), but significantly improved compared to pretest accuracies ( P  < 0.05). Accuracies for clinical scenarios #1 and #2 were 67.5 % and 60.3 %, respectively. Fellows had similar accuracies when compared to practicing gastroenterologists. Conclusions Using standardized methodology and a multidisciplinary approach, an AIEP management algorithm was created to improve patient care and alleviate physician and staff stress. In addition, we showed that a one-page educational document on perforations can significantly improve short-term and long-term physician knowledge, although periodic reeducation is needed.

Risk prediction of pancreatic cancer using AI analysis of pancreatic subregions in computed tomography images.

Early detection of Pancreatic Ductal Adenocarcinoma (PDAC) is complicated as PDAC remains asymptomatic until cancer advances to late stages when treatment is mostly ineffective. Stratifying the risk of developing PDAC can improve early detection as subsequent screening of high-risk individuals through specialized surveillance systems reduces the chance of misdiagnosis at the initial stage of cancer. Risk stratification is however challenging as PDAC lacks specific predictive biomarkers. Studies reported that the pancreas undergoes local morphological changes in response to underlying biological evolution associated with PDAC development. Accurate identification of these changes can help stratify the risk of PDAC. In this retrospective study, an extensive radiomic analysis of the precancerous pancreatic subregions was performed using abdominal Computed Tomography (CT) scans. The analysis was performed using 324 pancreatic subregions identified in 108 contrast-enhanced abdominal CT scans with equal proportion from healthy control, pre-diagnostic, and diagnostic groups. In a pairwise feature analysis, several textural features were found potentially predictive of PDAC. A machine learning classifier was then trained to perform risk prediction of PDAC by automatically classifying the CT scans into healthy control (low-risk) and pre-diagnostic (high-risk) classes and specifying the subregion(s) likely to develop a tumor. The proposed model was trained on CT scans from multiple phases. Whereas using 42 CT scans from the venous phase, model validation was performed which resulted in ~89.3% classification accuracy on average, with sensitivity and specificity reaching 86% and 93%, respectively, for predicting the development of PDAC (i.e., high-risk). To our knowledge, this is the first model that unveiled microlevel precancerous changes across pancreatic subregions and quantified the risk of developing PDAC. The model demonstrated improved prediction by 3.3% in comparison to the state-of-the-art method that considers the global (whole pancreas) features for PDAC prediction.

Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma.

In this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (-3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (-0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.