Upfront endoscopic necrosectomy or step-up endoscopic approach for infected necrotising pancreatitis (DESTIN): a single-blinded, multicentre, randomised trial.

BACKGROUND: Although the preferred management approach for patients with infected necrotising pancreatitis is endoscopic transluminal stenting followed by endoscopic necrosectomy as step-up treatment if there is no clinical improvement, the optimal timing of necrosectomy is unclear. Therefore, we aimed to compare outcomes between performing upfront necrosectomy at the index intervention versus as a step-up measure in patients with infected necrotising pancreatitis. METHODS: This single-blinded, multicentre, randomised trial (DESTIN) was done at six tertiary care hospitals (five hospitals in the USA and one hospital in India). We enrolled patients (aged ≥18 years) with confirmed or suspected infected necrotising pancreatitis with a necrosis extent of at least 33% who were amenable to endoscopic ultrasound-guided drainage. By use of computer-generated permuted block randomisation (block size four), eligible patients were randomly assigned (1:1) to receive either upfront endoscopic necrosectomy or endoscopic step-up treatment. Endoscopists were not masked to treatment allocation, but participants, research coordinators, and the statistician were. Lumen-apposing metal stents (20 mm diameter; 10 mm saddle length) were used for drainage in both groups. In the upfront group, direct necrosectomy was performed immediately after stenting in the same treatment session. In the step-up group, direct necrosectomy or additional drainage was done at a subsequent treatment session if there was no clinical improvement (resolution of any criteria of systemic inflammatory response syndrome or sepsis or one or more organ failure and at least a 25% percentage decrease in necrotic collection size) 72 h after stenting. The primary outcome was the number of reinterventions per patient to achieve treatment success from index intervention to 6 months' follow-up, which was defined as symptom relief in conjunction with disease resolution on CT. Reinterventions included any endoscopic or radiological procedures performed for necrosectomy or additional drainage after the index intervention, excluding the follow-up procedure at 4 weeks for stent removal. All endpoints and safety were analysed by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT05043415 and NCT04113499, and recruitment and follow-up have been completed. FINDINGS: Between Nov 27, 2019, and Oct 26, 2022, 183 patients were assessed for eligibility and 70 patients (24 [34%] women and 46 [66%] men) were randomly assigned to receive upfront necrosectomy (n=37) or step-up treatment (n=33) and included in the intention-to-treat population. At the time of index intervention, seven (10%) of 70 patients had organ failure and 64 (91%) patients had walled-off necrosis. The median number of reinterventions was significantly lower for upfront necrosectomy (1 [IQR 0 to 1] than for the step-up approach (2 [1 to 4], difference -1 [95% CI -2 to 0]; p=0·0027). Mortality did not differ between groups (zero patients in the upfront necrosectomy group vs two [6%] in the step-up group, difference -6·1 percentage points [95% CI -16·5 to 4·5]; p=0·22), nor did overall disease-related adverse events (12 [32%] patients in the upfront necrosectomy group vs 16 [48%] patients in the step-up group, difference -16·1 percentage points [-37·4 to 7·0]; p=0·17), nor procedure-related adverse events (four [11%] patients in the upfront necrosectomy group vs eight [24%] patients in the step-up group, difference -13·4 percentage points [-30·8 to 5·0]; p=0·14). INTERPRETATION: In stabilised patients with infected necrotising pancreatitis and fully encapsulated collections, an approach incorporating upfront necrosectomy at the index intervention rather than as a step-up measure could safely reduce the number of reinterventions required to achieve treatment success. FUNDING: None.

Constant-severe pain in chronic pancreatitis is associated with genetic loci for major depression in the NAPS2 cohort.

BACKGROUND: Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. STUDY: A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. RESULTS: Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10- 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). CONCLUSION: Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted. CLINICAL TRIALS REGISTRATION: Clinicaltriasl.gov.# NCT01545167.

A Rare Cause of Acute Pancreatitis in a Transgender Female.

Acute pancreatitis is defined as an acute inflammation of the pancreas and is most commonly caused by gallstones and alcohol followed by elevated triglycerides and medications. Estrogen as a cause of secondary hypertriglyceridemic pancreatitis is a rare but known phenomenon in females on hormonal therapy; however, it is not well described in the transgender female population. In this article, we present a case of a 31-year-old transgender female who developed acute, severe pancreatitis after a few months of using estrogen as transition therapy. To our knowledge, this is the third case report of a transgender female presenting with acute pancreatitis secondary to estrogen. Long-term supraphysiologic doses of sex hormones are required to maintain secondary sex characteristics placing this population at a higher risk of developing acute pancreatitis. Further research is needed to determine risk and screening methods to prevent this side effect.

Incidence of Venous Air Embolism During Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Known complications of endoscopic retrograde cholangiopancreatography (ERCP) include pancreatitis, bleeding, duodenal perforation, and venous air embolism (VAE). The aim of this study was to determine the incidence of VAE during ERCP and be able to differentiate high-risk versus low-risk ERCP procedures. METHODS: This is a prospective cohort study consisting of patients who underwent ERCP and were monitored with a precordial Doppler ultrasound (PDU) for VAE. PDU monitoring was digitally recorded and analyzed to confirm the suspected VAE. Demographic and clinical data related to the anesthetic care, endoscopic procedure, and intraoperative hemodynamics were analyzed. RESULTS: A total of 843 ERCP procedures were performed over a 15-month period. The incidence of VAE was 2.4% (20 patients). All VAE's occurred during procedures in which stent placement, sphincterotomy, biopsy, duct dilation, gallstone retrieval, cholangioscopy, or necrosectomy occurred. Ten of 20 (50%) of VAEs were associated with hemodynamic alterations. None occurred if the procedure was only diagnostic or for stent removal. Subanalysis for the type of procedure showed that VAE was statistically more frequent when stents were removed and then replaced or if a cholangioscopy was performed. CONCLUSIONS: The high incidence of VAE highlights the need for practitioners to be aware of this potentially serious event. Use of PDU can aid in the detection of VAE during ERCP and should be considered especially during high-risk therapeutic procedures. Detection may allow appropriate interventions before serious adverse events such as cardiovascular collapse occur.

International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club.

BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of Early CP is not possible using imaging criteria alone. If this were possible and early treatment instituted, the later, irreversible features and complications of CP could possibly be prevented. METHOD: An international working group supported by four major pancreas societies (IAP, APA, JPS, and EPC) and a PancreasFest working group sought to develop a consensus definition and diagnostic criteria for Early CP. Ten statements (S1-10) concerning Early CP were used to gauge consensus on the Early CP concept using anonymous voting with a 9 point Likert scale. Consensus required an alpha ≥0.80. RESULTS: No consensus statement could be developed for a definition of Early-CP or diagnostic criteria. There was consensus on 5 statements: (S2) The word "Early" in early chronic pancreatitis is used to describe disease state, not disease duration. (S4) Early CP defines a stage of CP with preserved pancreatic function and potentially reversible features. (S8) Genetic variants are important risk factors for Early CP and can add specificity to the likely etiology, but they are neither necessary nor sufficient to make a diagnosis. (S9) Environmental risk factors can provide evidence to support the diagnosis of Early CP, but are neither necessary nor sufficient to make a diagnosis. (S10) The differential diagnosis for Early CP includes other disorders with morphological and functional features that overlap with CP. CONCLUSIONS: Morphology based diagnosis of Early CP is not possible without additional information. New approaches to the accurate diagnosis of Early CP will require a mechanistic definition that considers risk factors, biomarkers, clinical context and new models of disease. Such a definition will require prospective validation.

Oxalate Concentrations in Human Gastrointestinal Fluid.

BACKGROUND AND PURPOSE: Urinary oxalate excretion is a risk factor for nephrolithiasis and is a result of endogenous metabolism and gastrointestinal processes. Gastrointestinal absorption of oxalate has been well demonstrated but to our knowledge evidence for secretion of oxalate is absent in humans. The objective of this study was to measure the amount and conformation of oxalate in the stomach and small intestine of adult subjects undergoing gastrointestinal endoscopy. MATERIALS AND METHODS: Eleven adults participated in this study. Gastrointestinal fluid was collected from the stomach and small intestine during endoscopy. A determination of the soluble and insoluble components of oxalate was made by centrifugation of the sample and subsequent acidification of the resultant pellet and supernatant. Samples were processed and the amount of oxalate was measured by ion chromatography, the limit of which is 1.6 µM. RESULTS: The majority of small intestinal samples contained some degree of oxalate. This is in contrast to the stomach where minimal oxalate was detected. There was a wide range of oxalate concentrations and a greater degree of insoluble oxalate in small intestinal samples. CONCLUSIONS: Our results suggest that some degree of oxalate secretion in the small intestine may occur in the fasted state while this is less likely in the stomach. Further studies are warranted to provide definitive evidence of gastrointestinal secretion of oxalate.

Incidence and predictors of post-ERCP pancreatitis in patients with suspected sphincter of Oddi dysfunction undergoing biliary or dual sphincterotomy: results from the EPISOD prospective multicenter randomized sham-controlled study.

BACKGROUND AND STUDY AIM: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a significant and potentially life-threatening adverse event and is common in patients with suspected sphincter of Oddi dysfunction (SOD). Here we aimed to identify predictors of the risk in this population. PATIENTS AND METHODS: The Evaluating Predictors and Interventions in SOD (EPISOD) study prospectively enrolled 214 post-cholecystectomy patients with SOD type III in seven US centers. Patients were randomized, using a 2:1 allocation, to sphincterotomy or sham procedure, irrespective of the results of sphincter of Oddi manometry. Patients in the sphincterotomy arm who had elevated pancreatic sphincter pressure were randomized to biliary only or to dual (biliary and pancreatic) sphincterotomy. All but one patient received prophylactic pancreatic stents, but none received pharmacological prophylaxis. Post ERCP pancreatitis (PEP) was defined as acute pancreatitis within the subsequent 7 days. Blinded research coordinators at each site called patients at 1 week post-procedure. RESULTS: PEP occurred in 26 patients, in 10.6 % (15/141) in the sphincterotomy arm and 15.1 % (11/73) in the sham arm; unadjusted relative risk 0.71 (95 % confidence interval [95 %CI] 0.34 - 1.46). PEP rate was not significantly different in patients who received sphincterotomy compared with those undergoing sham treatment. In addition, the proportion was not statistically different in those who received biliary sphincterotomy alone (12/94; 12.8 % [95 %CI 6.0 % - 19.5 %]) compared with dual sphincterotomy (3/47; 6.4 % [95 %CI 0.0 % - 13.4 %]). Multivariate analysis identified an interaction between duration of ERCP and sedation type (P < 0.02). CONCLUSION: The performance of biliary or dual sphincterotomy does not increase the risk of PEP in patients suspected of SOD. However, the high rate of PEP in patients with suspected SOD, despite pancreatic stenting in expert centers, is confirmed in this prospective study. The combined effect of duration of ERCP and sedation type on the development of PEP should be further explored.Clinicaltrials.gov registration: NCT00688662.

A novel composite endpoint to evaluate the gastrointestinal (GI) effects of nonsteroidal antiinflammatory drugs through the entire GI tract.

OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAID) not only cause damage to the upper gastrointestinal (GI) tract but also affect the lower GI tract. To date, there is no endpoint that evaluates serious GI events in the entire GI tract. The objective of this report is to introduce a novel composite endpoint that measures damage to the entire GI tract - clinically significant upper and lower GI events (CSULGIE) - in patients with NSAID-induced GI damage. METHODS: We reviewed the data from largescale, multicenter, randomized, clinical trials on lower GI toxicity associated with NSAID use. The rationale for using CSULGIE as a primary endpoint in 2 ongoing trials - the Celecoxib vs Omeprazole and Diclofenac for At-risk Osteoarthritis (OA) and Rheumatoid Arthritis (RA) Patients (CONDOR) trial and the Gastrointestinal Randomized Events and Safety Open-Label NSAID Study (GI-REASONS) - is also discussed. RESULTS: Previous randomized trials focused primarily on damage to the upper GI tract and often neglected the lower GI tract. The CSULGIE endpoint extends the traditional "perforation, obstruction, and bleeding" assessment of upper GI complications by including events in the lower GI tract (small/large bowel) such as perforation, bleeding, and clinically significant anemia. CONCLUSION: By providing clinicians with a new, descriptive language for adverse events through the entire GI tract, the CSULGIE endpoint has the potential to become a standard tool for evaluating the GI effects of a range of therapies.

A prospective evaluation of an algorithm incorporating routine preoperative endoscopic ultrasound-guided fine needle aspiration in suspected pancreatic cancer.

BACKGROUND: Whether tissue diagnosis is required in the preoperative evaluation of patients with suspected pancreatic cancer remains controversial. We prospectively evaluated the accuracy, safety, and potential impact on surgical intervention of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the preoperative evaluation of suspected pancreatic cancer. METHODS: All patients who underwent EUS-FNA at our institution (n = 547) over a 4.5-year period were enrolled. Patients underwent surgical exploration and resection based on their comorbidity status, evidence of resectability based on spiral computed tomography (CT) and EUS imaging reviewed in a multidisciplinary approach. RESULTS: Of 547 patients enrolled (median age 64 years, 60% male), 49% presented with obstructive jaundice. The operating characteristics of EUS-FNA of solid pancreatic masses were: sensitivity 95% (95% CI: 93.2-95.4), specificity 92% (95% CI: 86.6-95.7), positive predictive value 98% (95% CI: 97-99), negative predictive value 80% (95% CI: 74.9-82.7). The overall accuracy of EUS-FNA was 94.1% (95% CI: 92.0-94). Of the 414 true positive patients by EUS-FNA, 138 (33%) were explored. Of patients deemed operable by combined imaging, 42% had surgical resection. Eighty-two percent of true positive patients were ultimately found inoperable and received palliative therapy or chemotherapy. Of the 94 patients with true negative cytology based on extended follow-up, only 7 (7%) underwent surgical resection. Of those with false negative diagnoses (n = 24), 5 patients underwent exploration/resection based on detection of mass lesions by EUS. The remaining patients had unresectable disease. Mild self-limiting pancreatitis occurred in (0.91%). CONCLUSIONS: EUS-FNA is a safe and highly accurate method for tissue diagnosis in suspected pancreatic cancer. This approach allows for preoperative counseling of patients, minimizing surgeon's operative time in cases of unresectable disease, and avoids surgical biopsies in the majority of patients with inoperable disease. In addition, it allows for conservative management of patients with benign biopsies. We still, however, recommend exploration of patients with clinical scenario suspicious for pancreatic cancer, a mass found on EUS or CT, but inconclusive or negative cytology.

Relationship among hospital ERCP volume, length of stay, and technical outcomes.

BACKGROUND: The relationship between hospital procedure volume and outcome has been recognized for various specialties and procedures. Although increasingly used and in existence for 40 years, to date, data on the relationship between hospital volume and outcome of ERCP are scant. OBJECTIVE: We sought to examine health-related outcomes after ERCP in relation to hospital procedure volume. DESIGN: Secondary analysis of a national administrative database. We used the National Inpatient Sample (NIS) database to evaluate health-related outcomes among patients who underwent ERCP from 1998 to 2001. MAIN OUTCOME MEASUREMENTS: Logistic and multiple regression models were used to estimate the association of hospital ERCP volume with length of stay (LOS), rates of procedural failure, and mortality. Fixed effect models were used to adjust for all time invariant hospital characteristics for each hospital within the dataset. RESULTS: Data from 2629 hospitals that performed 199,625 ERCPs were evaluated. The median number of ERCPs performed in participating hospitals was 49 per year (range, 1-1004), with 25% of hospitals performing > or =100 ERCPs per year and 5% performing > or =200 per year. Significant trends in the relationship between volume and outcome were observed with respect to LOS and procedural failure: the median LOS was lower in high-volume (> or =200 ERCP/y) than low-volume (< or =100 ERCP/y) hospitals (6.9 vs 7.8 days, p < 0.0001) and the mean difference in expected LOS was 1.08 days (p < 0.0001). Multivariate regressions with hospital level fixed effects found significant negative relationships between procedure volume and procedure failure rates, but no significant effect on inpatient mortality rates was detected. LIMITATIONS: NIS database permits analyses of only inpatient ERCPs. It precludes analysis of procedural complications, reinterventions, and influence of individual provider volume on outcomes. CONCLUSIONS: Inpatients who undergo ERCP at high-volume hospitals have shorter LOS and lower procedural failure rates than those undergoing ERCP at low-volume hospitals. These findings have important implications for health care policy decision making and resource utilization.

Efficiency issues in sedation and monitoring.

Sedation and monitoring are key elements of the endoscopy process. There continues to be intense study of better methods for sedation and monitoring to improve the endoscopic "experience" for both patient and physicians alike. Our current practices will likely change in the future with technologic advances (monitoring) and expansion of our pharmacologic armamentarium (sedation).

Efecto de los antiinflamatorios no esteroidales sobre el tubo digestivo: prevención de lesiones / Effect of antiinflammatory non esteroidales agents on digestive tube: prevention of injuries

Los AINE son causa frecuente de lesiones gastrointestinales con morbimortalidad secundaria significativa. El AAS (Aspirina©) causa lesiones a corto plazo independiente de las dosis. En la prevención de estas lesiones, los bloqueadores de H2 no producen efecto, los bloqueadores de la bomba de protones son más eficaces que el misoprostol. Los factores de riesgo de enfermedad por AINE son edad mayor de 75 años, antecedentes de úlcera, sangrado gastrointestinal y enfermedad cardiovascular. Respecto del H pylori, la sola erradicación no bastaría como prevención; se debe realizar antes de iniciar un tratamiento con AINE a largo plazo. Diferentes estudios con inhibidores de la ciclooxigenasa-2 demuestran que no impiden la aparición de las úlceras gástricas, pero que, en comparación con AINE comunes, disminuyen las complicaciones de las úlceras. Por último, se entregan recomendaciones para evitar las complicaciones derivadas del uso de AINE, en las diversas situaciones clínicas, algunas de ellas en curso de debate

Patología digestiva alta y SIDA / Upper digestive pathology and AIDS

Para el manejo de la patología digestiva alta es necesario conocer el espectro de causas. Se debe determinar el estado de la infección por VIH para estratificar el riesgo de una infección oportunista. La historia es inmensamente útil para definir la etiología probable. También es importante definir la presencia de odinofagia. Es necesario hacer un diagnóstico diferencial endoscópico, con el objeto de tomar las muestras según corresponda. La toma de muestras y sus procesamiento se debe hacer de acuerdo con este diagnóstico diferencial

Diarrea en el paciente con SIDA / Diarrhea in AIDS patient

En el enfoque inicial de pacientes con diarrea y SIDA es esencial conocer la terapia antiviral que recibe, su riesgo de infección oportunista (estado de infección por VIH), antecedente de infección oportunista, la epidemiología de infecciones locales. La historia clínica para orientación de la ubicación de la diarrea (colon o intestino delgado), leucocitos fecales y estudio de deposiciones, mínimo 3, son esenciales. El espectro de agentes infecciosos es muy amplio. Los más frecuentes son el Criptosporidium (50 por ciento), en especial el intestino delgado; el CMV (20 por ciento), en especial en colon; y el Mycobacterium avium (MAC). Otros menos frecuentes son Microsporidium y Giardia. Se indica colonoscopía con toma de biopsias si los exámenes de deposiciones son negativos, algunos agentes escapan al diagnóstico aún con este tipo de estudio. Para el estudio del CMV puede bastar con una sigmoidoscopía y biopsias, pero su presentación endoscópica es variable y simula otras enfermedades (EII, linfoma, etc). Se propone un algoritmo para el estudio de la diarrea crónica en estos pacientes. Interesa destacar que algunas infecciones han disminuido en forma importante en pacientes con SIDA sometidos al nuevo esquema antiviral