Accuracy of Clinical Staging in Early-Stage Pancreatic Ductal Adenocarcinoma.

This study evaluates the accuracy of clinical staging in early-stage pancreatic ductal adenocarcinoma.

Irregular Z-Line: To Biopsy or Not to Biopsy?

The z-line refers to the squamocolumnar junction which marks the transition between the normal stratified squamous epithelium of the distal esophagus and the columnar epithelium of the gastric cardia. An "irregular" z-line refers to an irregular appearing squamocolumnar junction characterized by the presence of columnar mucosa less than 1 cm in length that extends above the gastroesophageal junction. In contrast, Barrett's esophagus is diagnosed when columnar mucosa of at least 1 cm is seen in the distal esophagus extending above the gastroesophageal junction with biopsies demonstrating specialized intestinal metaplasia. Current guidelines recommend against taking routine biopsies from a normal or irregular z-line in the absence of visible abnormalities and advise against endoscopic surveillance in this patient population, in large part due to multiple studies demonstrating lack of progression to advanced neoplasia such as high-grade dysplasia or esophageal adenocarcinoma in patients with an irregular z-line. Despite these recommendations, a sizable number of patients without Barrett's esophagus undergo biopsies from the z-line and are subsequently recommended to have surveillance endoscopies. Furthermore, patients with an irregular z-line are often mislabelled as Barrett's esophagus resulting in significant downstream consequences including higher healthcare costs and reduced health-related quality of life. In this review, we highlight the importance of landmark identification of the distal esophagus and gastroesophageal junction at the time of endoscopy, share recommendations from current guidelines related to the z-line, examine rates of neoplastic progression in those with an irregular z-line, discuss consequences of routinely biopsying an irregular z-line, and highlight strategies on how to approach an irregular z-line if seen on endoscopy. A careful, high-quality endoscopic examination can help to identify visible abnormalities at the z-line, which, if present, should be targeted for biopsies to rule out dysplasia and neoplasia.

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.

Rapid Diagnosis of Pneumocystis jirovecii Pneumonia and Respiratory Tract Colonization by Next-Generation Sequencing.

OBJECTIVES: To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia. METHODS: We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics. RESULTS: Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-ß-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved. CONCLUSION: Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.

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.

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.

Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.

OBJECTIVES: Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC). METHODS: Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response. RESULTS: Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively. CONCLUSIONS: Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.

Rapid diagnosis of fatal Nocardia kroppenstedtii bacteremic pneumonia and empyema thoracis by next-generation sequencing: a case report.

Nocardia species do not replicate as rapidly as other pyogenic bacteria and nocardial infections can be highly fatal, particularly in immunocompromised patients. Here, we present the first report of fatal Nocardia kroppenstedtii bacteremic pneumonia and empyema thoracis diagnosed by next-generation sequencing (NGS) using the Oxford Nanopore Technologies' MinION device. The bacterium was not identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Due to its low equipment cost, short turn-around-time, and portable size, the Oxford Nanopore Technologies' MinION device is a useful platform for NGS in routine clinical microbiology laboratories.

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.

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.

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.

Endoscopic closure of refractory upper GI-tracheobronchial fistulas with a novel occluder: a prospective, single-arm, single-center study (with video).

BACKGROUND AND AIMS: Upper GI-tracheobronchial fistula is a morbid condition with high mortality. It is a challenge for endoscopists because currently available treatments have severe limitations. In this study we assessed the efficacy and safety of an occluder we invented for endoscopic closure of refractory upper GI-tracheobronchial fistulas. METHODS: This was a prospective, single-arm, single-center trial conducted between September 2020 and March 2022. All patients undergoing occluder placement were eligible to enroll. The primary endpoints were clinical success rate (CSR) and complete closure rate (CCR) at 3 months and safety. Secondary efficacy endpoints were technical success rates, CSRs and CCRs at 1 and 6 months, near-complete closure rates, change from baseline in body mass index (BMI), and health-related quality of life (HRQoL) at 1, 3, and 6 months. RESULTS: Twenty-eight patients (mean age, 63.2 years; 23 men) were enrolled. Eighteen through-the-scope occluders (TTSOs) and 10 through-the-overtube occluders (TTOOs) were implanted, with a technical success rate of 100%. The mean procedure time for the TTSO and TTOO groups were 28.0 ± 8.0 minutes and 31.8 ± 7.7 minutes, respectively. The CSRs at 1, 3, and 6 months were 92.9%, 96.4%, and 92.0% and the CCRs were 60.7%, 60.7%, and 60.0%, respectively. The mean BMI at 3 and 6 months and HRQoL at 1, 3, and 6 months were significantly increased compared with baseline (P < .05). Two completely occluded fistulas had 1-sided or complete healing by coverage of granulation tissue and re-epithelialized mucosa at a follow-up of 6 and 12 months. All 14 adverse events were either mild and transient or easily corrected. CONCLUSIONS: Our clinical outcomes suggest that this novel GI occluder is a safe and effective salvage option for patients with refractory upper GI-tracheobronchial fistulas. (Clinical trial registration number: ChiCTR2000038566.).

Impact of COVID-19 infection and vaccination in pancreatobiliary IgG4-related disease patients: An international multicenter study.

BACKGROUND AND AIM: Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown. METHODS: Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort. RESULTS: Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed. CONCLUSION: While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

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.

Chemical Exchange Saturation Transfer for Pancreatic Ductal Adenocarcinoma Evaluation.

OBJECTIVES: The aims of the study are to evaluate the feasibility of using pH-sensitive magnetic resonance imaging, chemical exchange saturation transfer (CEST) in pancreatic imaging and to differentiate pancreatic ductal adenocarcinoma (PDAC) with the nontumor pancreas (upstream and downstream) and normal control pancreas. METHODS: Sixteen CEST images with PDAC and 12 CEST images with normal volunteers were acquired and magnetization transfer ratio with asymmetric analysis were measured in areas of PDAC, upstream, downstream, and normal control pancreas. One-way analysis of variance and receiver operating characteristic curve were used to differentiate tumor from nontumor pancreas. RESULTS: Areas with PDAC showed higher signal intensity than upstream and downstream on CEST images. The mean (standard deviation) values of magnetization transfer ratio with asymmetric analysis were 0.015 (0.034), -0.044 (0.030), -0.019 (0.027), and -0.037 (0.031), respectively, in PDAC area, upstream, downstream, and nontumor area in patient group and -0.008 (0.024) in normal pancreas. Significant differences were found between PDAC and upstream ( P < 0.001), between upstream and normal pancreas ( P = 0.04). Area under curve is 0.857 in differentiating PDAC with nontumor pancreas. CONCLUSIONS: pH-sensitive CEST MRI is feasible in pancreatic imaging and can be used to differentiate PDAC from nontumor pancreas. This provides a novel metabolic imaging method in PDAC.