Successful management of bile duct injury with duodenal perforation using endoscopic naso-pancreatic drainage and fully covered self-expandable metallic stent deployment.

Video 1A case of bile and pancreatic duct injury with duodenal perforation during endoscopic submucosal dissection for superficial duodenal epithelial neoplasia.

Non-interventional Management of Asymptomatic Diminutive Choledocholithiasis Versus Endoscopic Extraction in Consecutive Patients.

BACKGROUND: Current guidelines recommend treating choledocholithiasis, regardless of symptoms or stone size, with endoscopic retrograde cholangiopancreatography (ERCP). However, asymptomatic choledocholithiasis, discovered incidentally on imaging, may carry a higher risk of ERCP-related adverse events, and some asymptomatic and diminutive stones may not cause biliary adverse events during extended follow-up. Therefore, we aimed to clarify the best treatment strategies for asymptomatic choledocholithiasis based on stone size. METHODS: We retrospectively identified patients with incidental imaging-found asymptomatic diminutive (≤ 4 mm) or non-diminutive (> 4 mm) choledocholithiasis and divided them into two groups: those who did not undergo ERCP and were treated when complications arose (on-demand group) and those who underwent ERCP before being symptomatic (intervention group). Adverse events were defined as any biliary or pancreatic complication related to ERCP or arising during observation or after intervention. The primary outcome was the adjusted overall adverse event-free survival using the propensity score-based matching weights method comparing the two groups of stone size. RESULTS: Among 148 patients identified (median follow-up period, 969 days), 68 had diminutive stones and 80 had non-diminutive stones. Of the 68 patients with diminutive stones, 51 were in the on-demand group and 17 in the intervention group. The overall adjusted adverse event-free survival was significantly higher in the on-demand group for diminutive stones (97.4% and 70.1%, respectively, at 3 years; p = 0.01). DISCUSSION: Patients with incidental imaging-detected asymptomatic diminutive choledocholithiasis may benefit from clinical observation, pursuing ERCP when symptoms develop.

Successful radiotherapy for recurrent obstructive pancreatitis secondary to pancreatic metastasis from cervical squamous-cell carcinoma.

Metastatic pancreatic cancer is a rare condition and cases of pancreatic metastasis from cervical cancer are infrequently reported. Furthermore, the incidence rates of pancreatic tumors as the cause of pancreatitis and of pancreatitis in patients with pancreatic tumors are similarly low. Pancreatitis may occur when a tumor obstructs the pancreatic duct. This condition may be difficult to manage and significantly reduces the quality of life because of severe abdominal pain. Here, we present a rare case of obstructive pancreatitis caused by pancreatic metastasis from cervical squamous-cell carcinoma, pathologically confirmed using endoscopic ultrasonography-guided fine-needle biopsy and treated with palliative irradiation to achieve rapid therapeutic relief. It is important to obtain appropriate tissue samples, confirm the pathological diagnosis, and compare the pathological findings with those of the primary tumor to select the appropriate treatment for obstructive pancreatitis caused by a metastatic pancreatic tumor.

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants.

Importance: Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. Objective: To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A. Design, Setting, and Participants: This case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome-associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome-associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021. Main Outcomes and Measures: For the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome-associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV. Results: In total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77). Conclusions and Relevance: In this case series, the presence of PGVs in 9 cancer syndrome-associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.

Association between computerized tomography (CT) study of body composition and severity of acute pancreatitis: Use of a novel Z-score supports obesity paradox.

BACKGROUND & AIMS: The association between body composition parameters measured on computed tomography (CT) and severity of acute pancreatitis (AP) is conflicting because these composition parameters vary considerably by sex and age. We previously developed normative body composition data, in healthy subjects. Z-score calculated from the normative data gives age and sex adjusted body composition parameters. We studied the above association using this novel Z-score in a large cohort of patients with AP. METHODS: Between January 2014 and March 2018, patients admitted with AP and had CT scans within a week of admission, were enrolled. Body composition data including skeletal muscle (SM), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were calculated from the CT scan using deep learning automated algorithm. Then we converted the value to Z-score, and then compared the same score between mild AP, moderately severe AP and severe AP defined by revised Atlanta criteria. RESULTS: Out of 514 patients, 336 (65.4%) are mild AP, 130 (25.3%) moderately severe AP, and 48 (9.3%) severe AP. Patients with moderately severe AP had significantly lower SM-z-score than those with mild AP (1.21 vs1.73, p = 0.048) and patients with severe AP had significantly lower SAT-z-score than those with mild AP (0.70 vs.1.29, p = 0.016). VAT-z-score was not significantly different between three groups. (p = 0.76). CONCLUSION: Lower SM-z-score and SAT-z-score were associated with moderately severe and severe types of AP, respectively. Future prospective studies in patients with AP using Z-scores, may define the association between body composition and severity of AP, and explain the inconsistencies reported in previous studies.

Microangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described. MATERIALS AND METHODS: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival. RESULTS: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/µL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P < .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12). CONCLUSION: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone.

Superiority of urgent vs early endoscopic hemostasis in patients with upper gastrointestinal bleeding with high-risk stigmata.

BACKGROUND: Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). METHODS: Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. RESULTS: HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0-4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5-19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09-0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16-0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P < 0.001). CONCLUSIONS: A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.

Diagnosing Biliary Strictures: Distinguishing IgG4-Related Sclerosing Cholangitis From Cholangiocarcinoma and Primary Sclerosing Cholangitis.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

Impact of Enteral Nutrition Within 24 Hours Versus Between 24 and 48 Hours in Patients With Severe Acute Pancreatitis: A Multicenter Retrospective Study.

OBJECTIVES: In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown. METHODS: We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality. RESULTS: Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29). CONCLUSIONS: Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment.

Pancreatic cancer is the most lethal solid malignancy, and the number of patients with pancreatic cancer is increasing. Systemic chemotherapies are often ineffective for such patients, and there is an urgent need for personalized medicine. Unlike other types of cancer, personalized treatments for pancreatic cancer are still in development. Consequently, pancreatic cancer is less sensitive to anticancer drugs and is often refractory to common treatments. Therefore, advances in personalized medicine for pancreatic cancer are necessary. This review examined advances in personalized medicine for pancreatic cancer, including the use of endoscopic ultrasound (EUS)-guided sampling. EUS-guided sampling is widely used for diagnosing pancreatic tumors and is expected to be applied to sampled tissues. Additionally, there has been an increase in clinical research using EUS-guided sampling. The combination of precision medicine using genomic testing and pharmacological profiles based on high-throughput drug sensitivity testing using patient-derived organoids is expected to revolutionize pancreatic cancer treatment.

Endoscopic Diagnosis of Biliary Stricture Combined with Digital Cholangioscope: A Case Series.

The endoscopic diagnosis of biliary tract lesions is applied as a non-invasive method; however, its diagnostic accuracy is not yet high. Moreover, digital cholangioscopy is used for directly visualizing the inside of the bile duct, resulting in a more precise biopsy. We present the case series of the outcomes of diagnosis using digital cholangioscopy in patients who underwent cholangioscopy for the evaluation of biliary stenosis in our department between January 2014 and March 2021. The controls were those who underwent a biopsy for biliary stenosis with conventional endoscopic retrograde cholangiopancreatography (ERCP). Background data for each case were collected, and the clinical outcomes by biopsy were evaluated, focusing on the accuracy of the diagnosis. Cholangioscopy was performed in 15 cases, while a conventional biopsy by ERCP was performed in 172 cases. Nine of 15 cases (60.0%) were diagnosed with cholangiocarcinoma. The number of specimens obtained through conventional ERCP and cholangioscopy was 2.5 ± 1.3 and 3.3 ± 1.5, respectively (p = 0.043). The diagnostic accuracy of conventional ERCP and cholangioscopy were 65.7% (113 of 172 cases) and 100%, respectively, which was significantly higher in the group with cholangioscopy. Digital cholangioscopy is useful when the diagnosis of the biliary stricture using the conventional ERCP method is difficult.

Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

OBJECTIVES: Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP. METHODS: A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis. RESULTS: Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047). CONCLUSIONS: We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.