Germline multigene panel testing in acute and chronic pancreatitis.

BACKGROUND/OBJECTIVES: Germline genetic testing is recommended for younger patients with idiopathic pancreatitis but there has been a lack of consensus in recommendations for those over age 35. We aimed to analyze the results of genetic testing among subjects of varying ages. METHODS: Individuals who underwent germline multigene testing for pancreatitis susceptibility genes (CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1) through a large commercial laboratory between 2017 and 2022 were included. Test results and information collected from test requisition forms were evaluated. Multivariable logistic regression models were performed to identify factors associated with a positive pancreatitis panel (pathogenic, likely pathogenic, and/or increased risk variants) in pancreatitis-related genes. RESULTS: Overall, 2,468 subjects with primary indication of acute pancreatitis (AP) (n = 401), chronic pancreatitis (CP) (n = 631), pancreatic cancer (n = 128), or other indications (n = 1,308) completed germline testing. Among patients with AP or CP, the prevalence of any positive result for those <35 versus ≥35 years of age was 32.1% and 24.5% (p = 0.007), and the prevalence of a clinically meaningful result was 10.8% and 5.4%, respectively (p = 0.001). Positive family history of pancreatitis was associated with increased odds ratio (OR) of 8.59 (95% confidence interval (CI) 2.92-25.25) for a clinically significant panel result while each 5-year increase in age at test completion had lower odds (OR 0.89, 95% CI 0.83-0.95). CONCLUSIONS: The highest prevalence of pathogenic variants is seen in younger individuals with a positive family history of pancreatitis. However, clinically meaningful results are identified in older subjects, suggesting that genetic counseling and testing should be considered for all age groups.

Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study.

Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort. Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 µg/g; severe FE-1 level ≤100 µg/g; mild FE-1 101-200 µg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398. Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%). Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening. Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

Immune markers of severe acute pancreatitis.

PURPOSE OF REVIEW: Acute pancreatitis is a common acute inflammatory disorder of the pancreas, and its incidence has been increasing worldwide. Approximately 10% of acute pancreatitis progresses to severe acute pancreatitis (SAP), which carries significant morbidity and mortality. Disordered immune response to pancreatic injury is regarded as a key event that mediates systemic injury in SAP. In this article, we review recent developments in immune biomarkers of SAP and future directions for research. RECENT FINDINGS: Given the importance of the NLRP3-inflammasome pathway in mediating systemic inflammatory response syndrome and systemic injury, recent studies have investigated associations of SAP with systemic levels of activators of NLRP3, such as the damage associated molecular patterns (DAMPs) for the first time in human SAP. For example, circulating levels of histones, mitochondrial DNAs, and cell free DNAs have been associated with SAP. A panel of mechanistically relevant immune markers (e.g., panel of Angiopoeitin-2, hepatocyte growth factor, interleukin-8 (IL-8), resistin and sTNF-α R1) carried higher predictive accuracies than existing clinical scores and individual immune markers. Of the cytokines with established relevance to SAP pathogenesis, phase 2 trials of immunotherapies, including tumor necrosis factor (TNF)-alpha inhibition and stimulation of IL-10 production, are underway to determine if altering the immunologic response can reduce the severity of acute pancreatitis (AP). SUMMARY: Circulating systemic levels of various DAMPs and a panel of immune markers that possibly reflect activities of different pathways that drive SAP appear promising as predictive biomarkers for SAP. But larger multicenter studies are needed for external validation. Studies investigating immune cellular pathways driving SAP using immunophenotyping techniques are scarce. Interdisciplinary efforts are also needed to bring some of the promising biomarkers to the bedside for validation and testing for clinical utility. Studies investigating the role of and characterization of altered gut-lymph and gut-microbiota in severe AP are needed.

SPARC - A multi-disciplinary team program for retroperitoneal sarcoma: the Royal Prince Alfred Hospital and Chris O'Brien Lifehouse Collaboration.

BACKGROUND: The Royal Prince Alfred Hospital (RPAH) and Chris O'Brien Lifehouse (COBLH) established a formal Sarcoma of the Pelvic and Abdominal Retroperitoneum Collaboration (SPARC) in November 2020. An established multidisciplinary team (MDT) with the aims to centralise patient referrals and treatment, establish database and research, coordinate surgical resections is critical in improving patient outcomes and quality of life. METHODS: A prospective database was established in October 2021. Clinical, pathological and radiological data points were recorded for all patients since the inception of SPARC. Quality of Life questionnaires were included and follow-up planned regularly for 5 years. RESULTS: From November 2020 to Feb 2024, 294 new referrals were discussed at the MDT meeting. Majority were from the metropolitan area (182) followed by regional NSW (87), interstate (20) and five internationals. 141 operations were performed during this period compared to 119 operations from 2010 to November 2020 in RPAH. The inception of the SPARC program has resulted in exponential growth in operations, improving from the previous rate of 15 cases annually to 35. Liposarcomas followed by leiomyosarcomas are the most common types of sarcomas resected. The majority were extended resections (81.6%) and 22% were pelvic exenterations. Overall R0 rate is 54.6%, R1 38.3% and R2 1.4% (131 (92.9%) had R0/R1 resections. Overall complication rate is 35.5% with one in-hospital mortality. CONCLUSION: Success and expansion of a robust retroperitoneal sarcoma program requires a collaborative surgical approach, an MDT meeting, centralized referral process, and a research team in specialized tertiary institutions.

Pelvic exenteration for locally advanced and recurrent prostate cancer.

Locally advanced or recurrent prostate cancer which invades adjacent pelvic organs, bone or other soft tissue structures is a rare situation. This study aimed to report the outcomes of ten consecutive patients who underwent total pelvic exenteration for prostate cancer at a high-volume specialist centre. Two patients had locally advanced primary tumours, while eight had locally recurrent prostate cancer. Median operating time, blood loss, ICU stay, and hospital stay was 12.2 h (range 9.6-13.8), 2500 ml (500-3000), 4.5 days (2-7) and 36 days (21-78), respectively. There was no inpatient, 30-day, or 90-day mortality. Six patients developed a Clavien-Dindo III complication. R0 resection was achieved in eight patients. Median follow up was 16 months (range 2-77). At last follow up, five patients were alive without disease. These findings suggest that pelvic exenteration for locally advanced and recurrent prostate cancer is safe and represents a potentially curative treatment option for highly selected patients.

Development of a novel CT-based index for predicting the number of extracorporeal shockwave lithotripsy (ESWL) sessions required for successful fragmentation of obstructing pancreatic duct stones.

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Critical appraisal of machine learning prognostic models for acute pancreatitis: protocol for a systematic review.

Acute pancreatitis (AP) is an acute inflammatory disorder that is common, costly, and is increasing in incidence worldwide with over 300,000 hospitalizations occurring yearly in the United States alone. As its course and outcomes vary widely, a critical knowledge gap in the field has been a lack of accurate prognostic tools to forecast AP patients' outcomes. Despite several published studies in the last three decades, the predictive performance of published prognostic models has been found to be suboptimal. Recently, non-regression machine learning models (ML) have garnered intense interest in medicine for their potential for better predictive performance. Each year, an increasing number of AP models are being published. However, their methodologic quality relating to transparent reporting and risk of bias in study design has never been systematically appraised. Therefore, through collaboration between a group of clinicians and data scientists with appropriate content expertise, we will perform a systematic review of papers published between January 2021 and December 2023 containing artificial intelligence prognostic models in AP. To systematically assess these studies, the authors will leverage the CHARMS checklist, PROBAST tool for risk of bias assessment, and the most current version of the TRIPOD-AI. (Research Registry ( http://www.reviewregistry1727 .).

Alterations in exocrine pancreatic function after acute pancreatitis.

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps.

Optimizing theatre utilization for abscess drainage: going beyond priority categories.

BACKGROUND: Day-only emergency surgery for abscess drainage is poorly implemented in Australia. This study assessed the feasibility, outcomes, cost, and impact of an acute day-only surgery (ADOS) program. METHOD: A retrospective pre-post implementation study of patients requiring abscess drainage in theatre was performed. Following implementation of an ADOS program for abscess management, eligible patients were discharged from the emergency department and prioritized first on the following day's emergency list. Outcomes from the first 12 months of the ADOS era were compared with those of the preceding 6 months (pre-ADOS). Primary outcome was length of hospital stay (LOS). Secondary outcomes included 30-day complications, admission costs, and impact on overall emergency theatre workflow (measured by emergency appendicectomy metrics). RESULTS: Overall, 266 patients during the ADOS era (including 95 eligible for the ADOS pathway) were compared with 115 patients during the pre-ADOS era. Baseline characteristics were comparable. Median LOS was shorter during the ADOS era (21.9 h (IQR 11.8-43.3) vs. 30.1 h (IQR 24.7-48.8), P < 0.001). Median LOS was 10.2 h (IQR 8.9-13.1) for patients on the ADOS pathway. There were no significant differences in 30-day complications (9.3% vs. 9.5%), emergency department re-presentations (7.4% vs. 5.1%), or abscess recurrence (5.6% vs. 5.7%). Average cost per patient was lower during the ADOS era ($4155 vs. $4916, p = 0.005). ADOS did not appear to materially impact other emergency procedures. CONCLUSION: ADOS for abscess drainage is feasible, safe, and produces cost savings, while being implemented without significant additional resources.

Impact of Intraoperative Decision-Making on Pathological Margin Status in Patients Undergoing Pelvic Exenteration for Locally Recurrent Rectal Cancer.

BACKGROUND: A key component of preoperative preparation for pelvic exenteration surgery is the development of an operative plan in a multidisciplinary setting based on the extent of local tumor invasion on preoperative imaging. Changes to the extent of resection or operative plan may occur intraoperatively based on intraoperative findings. OBJECTIVE: To report the frequency and extent of intraoperative deviation from the planned extent of resection during pelvic exenteration for locally recurrent rectal cancer and determine whether this resulted in a more or less radical resection. DESIGN: Retrospective observational study. SETTINGS: A high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between January 2015 and December 2020. MAIN OUTCOME MEASURES: Frequency and extent of intraoperative deviation from the planned extent of resection, R0 resection rate. RESULTS: One hundred thirty-six patients underwent pelvic exenteration for locally recurrent rectal cancer, of whom 110 (81%) had R0 resection margins. Twelve patients were excluded because of missing information, and 49 patients (40%) had a change to the operative plan. Operative changes were major in 30 patients (61%), more radical in 40 patients (82%), and margin relevant in 24 patients (49%). In patients in whom there was a change to the operative plan and R0 resection was achieved, the median distance to a relevant margin was 2.5 mm (range, 0.1-10 mm). Of 8 patients with a change in operative plan and R1 resection, 3 were margin relevant, of whom all were considered major, and 2 were more radical and 1 was less radical. LIMITATIONS: Generalizability outside of specialist units may be limited. CONCLUSIONS: Intraoperative changes to the planned extent of resection occur commonly and most often result in an unanticipated major or more radical resection. Such changes may contribute to high rates of R0 resection margins in specialist pelvic exenteration units that use an ultraradical approach in these patients. See Video Abstract . IMPACTO DE LA TOMA DE DECISIONES INTRAOPERATORIA SOBRE EL ESTADO DEL MARGEN PATOLGICO EN PACIENTES SOMETIDOS A EXENTERACIN PLVICA POR RECURRENCIA LOCAL EN CNCER DE RECTO: ANTECEDENTES:Un componente clave de la preparación preoperatoria para exenteración pélvica es el desarrollo de un plan quirúrgico en un entorno multidisciplinario, basado en el grado de invasión tumoral local en las imágenes preoperatorias. Es posible que se produzcan cambios intraoperatorios en la extensión de la resección o en el plan quirúrgico según los hallazgos intraoperatorios.OBJETIVO:Informar la frecuencia y la extensión de la desviación intraoperatoria de la extensión planificada de la resección durante la exenteración pélvica para el cáncer de recto localmente recurrente, y si esto resultó en una resección más o menos radical.DISEÑO:Estudio observacional retrospectivo.ESCENARIO:Un centro de exenteración pélvica de alto volumen.PACIENTES:Pacientes sometidos a exenteración pélvica por cáncer de recto localmente recurrente entre enero de 2015 y diciembre de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia y extensión de desviación intraoperatoria de la extensión planeada de resección, tasa de resección R0.RESULTADOS:136 pacientes fueron sometidos a exenteración pélvica por cáncer de recto localmente recurrente, de los cuales 110 (81%) tuvieron márgenes de resección R0. 12 pacientes fueron excluidos por falta de información y 49 pacientes (40%) tuvieron un cambio en el plan quirúrgico. Los cambios operatorios fueron mayores en 30 pacientes (61%), más radicales en 40 pacientes (82%) y con relevancia sobre márgenes en 24 pacientes (49%). En los pacientes en los que hubo un cambio en el plan quirúrgico y se logró la resección R0, la distancia mediana hasta un margen relevante fue de 2.5 mm (rango 0.1-10 mm). De ocho pacientes con un cambio en el plan quirúrgico y resección R1, tres tuvieron relevancia sobre márgenes de los cuales todos se consideraron mayores, dos fueron más radicales y uno fue menos radical.LIMITACIONES:La generalización fuera de las unidades especializadas puede ser limitada.CONCLUSIONES:Los cambios intraoperatorios en la extensión planificada de la resección ocurren comúnmente y con mayor frecuencia resultan en una resección mayor imprevista y más radical. Dichos cambios pueden contribuir a altas tasas de márgenes de resección R0 en unidades especializadas en EP que emplean un enfoque ultrarradical en estos pacientes. (Traducción-Dr. Jorge Silva Velazco ).

Outcomes Following Pelvic Exenteration for Locally Recurrent Rectal Cancer With and Without En Bloc Sacrectomy.

BACKGROUND: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit. OBJECTIVE: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer. DESIGN: Comparative cohort study with retrospective analysis of prospectively collected data. SETTING: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022. MAIN OUTCOME MEASURES: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes. RESULTS: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p = 0.059). Quality-of-life scores were not significantly different across physical component ( p = 0.346), mental component ( p = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p = 0.679) scores at 24-month follow-up. LIMITATIONS: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis. CONCLUSIONS: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract . RESULTADOS DESPUS DE LA EXENTERACIN PLVICA PARA EL CNCER DE RECTO CON RECURRENCIA LOCAL, CON Y SIN SACRECTOMA EN BLOQUE: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy ).

A Review on Endoscopic Management of Acute Cholecystitis: Endoscopic Ultrasound-Guided Gallbladder Drainage and Endoscopic Transpapillary Gallbladder Drainage.

A percutaneous cholecystostomy tube (PCT) is the conventionally favored nonoperative intervention for treating acute cholecystitis. However, PCT is beset by high adverse event rates, need for scheduled reintervention, and inadvertent dislodgement, as well as patient dissatisfaction with a percutaneous drain. Recent advances in endoscopic therapy involve the implementation of endoscopic transpapillary drainage (ETP-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), which are increasingly preferred over PCT due to their favorable technical and clinical success combined with lower complication rates. In this article, we provide a comprehensive review of the literature on EUS-GBD and ETP-GBD, delineating instances when clinicians should opt for endoscopic management and highlighting potential risks associated with each approach.

Comparison of urological outcomes and quality of life after pelvic exenteration: partial vs radical cystectomy.

OBJECTIVE: To compare perioperative morbidity, functional and quality-of-life (QoL) outcomes in patients with partial cystectomy vs radical cystectomy as part of pelvic exenteration. PATIENTS AND METHODS: Retrospective analysis of a prospectively maintained database of pelvic exenteration patients (1998-2021) was conducted in a single centre. Study outcomes included postoperative complications, quality-of-life, functional and stoma-related outcomes. The 36-item Short-Form Health Survey Physical and Mental Health Components, Functional Assessment of Cancer Therapy-Colorectal questionnaires and Distress Thermometer were available pre- and postoperatively. QoL outcomes were compared at the various time points. Stoma embarrassment and care scores were compared between patients with a colostomy, urostomy, and both. RESULTS: Urological complications were similar between both groups, but patients with partial cystectomy experienced less wound-related complications. Overall, 34/81 (42%) partial cystectomy patients reported one or more long-term voiding complication (i.e., incontinence [17 patients], frequency [six], retention [three], high post-voiding residuals [10], permanent suprapubic catheter/indwelling catheter [14], recurrent urinary tract infection [nine], percutaneous nephrostomy [three], progression to urostomy [three]). The QoL improved following surgery in both the partial and radical cystectomy groups, differences between cohorts were not significant. Patients with two stomas reported higher embarrassment scores than patients with one stoma, although this did not result in more difficulties in stoma care. CONCLUSIONS: Partial cystectomy patients have fewer postoperative wound-related complications than radical cystectomy patients, but often experience long-term voiding issues. The QoL outcomes are similar for both cohorts, with significant improvement following surgery.

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol.

AIMS: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. METHODS: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). RESULTS: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). CONCLUSION: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

Pelvic exenteration for chronic fistulating pelvic sepsis after multimodal treatment of pelvic malignancy.

BACKGROUND: Chronic fistulating pelvic sepsis is an uncommon complication of multimodal treatment of visceral pelvic tumours. Radical multi-visceral resection is reserved for patients with persistent, debilitating symptoms despite less invasive treatments and for which there is minimal published data. This study aimed to report the rates of morbidity and long-term sepsis control after pelvic exenteration for chronic fistulating pelvic sepsis. METHODS: This retrospective cohort study was conducted at a high-volume pelvic exenteration referral centre. Patients who underwent pelvic exenteration for chronic fistulating pelvic sepsis between September 1994 and January 2023 after previous treatment for pelvic malignancy were included. Data relating to postoperative morbidity, mortality and the rate of recurrent pelvic sepsis or fistulae were retrospectively collected. RESULTS: 19 patients who underwent radical resection for chronic fistulating pelvic sepsis after previous pelvic cancer treatment were included. 11 patients were male (58 %) and median age was 62 years (range 42-79). Previously treated rectal (8 patients, 42 %), prostate (5, 26 %) and cervical cancer (5, 26 %) were most common. 18 patients (95 %) had previously received high-dose pelvic radiotherapy, and 14 (74 %) had required surgical resection. Total pelvic exenteration was performed in 47 % of patients, total cystectomy in 68 % and major pubic bone resection in 37 %. There was no intraoperative or postoperative mortality. Major complication rate was 32 %. 12-month readmission rate was 42 %. At last follow up, 74 % had no signs or symptoms of persisting pelvic sepsis. CONCLUSIONS: Pelvic exenteration for refractory pelvic sepsis following treatment of malignancy is safe and effective in selected patients.

Incident diabetes following acute pancreatitis in a multicenter prospective observational cohort.

Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and risk factors. We evaluated data from a prospective, multicenter observational cohort study that enrolled adults hospitalized with AP between 2017 and 2021 and followed them for one year. Ninety-eight participants who completed 12-month follow-up were included in this analysis. Diabetes status was assessed using a combination of measured glycated hemoglobin (HbA1c) at predetermined time intervals or physician diagnosis. In 68 participants without diabetes at enrollment, the cumulative incidence of new-onset diabetes was 4.4 % (n = 3) at 3 months and 10.3 % (n = 7) at 12 months. No differences were observed in demographic or pancreatitis-related characteristics between those who did versus did not develop diabetes, in part due to small sample size. In summary, new-onset diabetes was identified in approximately 10 % within one year after an episode of AP. Larger prospective studies are needed to further define the incidence, risk factors, and mechanisms of diabetes and pre-diabetes following AP. NCT03063398.

Dilation balloon-occlusion technique for EUS-guided gastrojejunostomy.

Video 1Dilation balloon-occlusion technique for EUS-guided gastrojejunostomy.

Pelvic Exenteration for Squamous Cell Carcinoma of the Anus: Oncological, Morbidity, and Quality-of-Life Outcomes.

BACKGROUND: Salvage surgery is the only potentially curative treatment option for recurrent squamous cell carcinoma of the anus. Where adjacent pelvic viscera, soft tissues, and bone are involved, pelvic exenteration with a wide perineal excision may be required to ensure clear surgical margins and increase the likelihood of long-term survival. OBJECTIVE: To report oncological, morbidity, and quality-of-life outcomes of pelvic exenteration for anal squamous cell carcinoma. DESIGN: Cohort study with retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Those who underwent pelvic exenteration for anal squamous cell carcinoma between 1994 and 2022. MAIN OUTCOME MEASURES: Local recurrence-free and overall survival, intraoperative and postoperative complication rates, R0 resection rate, and long-term quality-of-life outcomes. RESULTS: Of 958 patients who underwent pelvic exenteration, 66 (6.9%) had anal squamous cell carcinoma. Thirty-two patients (48.5%) were male and the median age was 57 years (range, 31-79). Ten patients (15%) had primary anal squamous cell carcinoma, 49 (74%) had a recurrent tumor, and 7 (11%) had a re-recurrent tumor. Twenty-two patients (33%) and 16 patients (24%) had a major complication and unplanned return to the operating theater, respectively. Of the 62 patients who underwent pelvic exenteration with curative intent, 50 (81%) had R0 resection, and the 5-year overall and local recurrence-free survival rates were 41% and 37%, respectively. R0 resection was associated with a higher 5-year overall survival (50% vs 8%, p < 0.001). The mental health component scores and several individual quality-of-life domains presented improved trajectories postoperatively (all p values <0.05). LIMITATIONS: The generalizability of the findings outside specialist pelvic exenteration centers may be limited. CONCLUSIONS: Morbidity, long-term survival, and quality-of-life outcomes after pelvic exenteration for anal squamous cell carcinoma are comparable to published outcomes of pelvic exenteration for other tumor types. EXENTERACIN PLVICA POR CARCINOMA EPIDERMOIDE DE ANO RESULTADOS ONCOLGICOS, DE MORBILIDAD Y DE CALIDAD DE VIDA: ANTECEDENTES:La cirugía de rescate es la única opción de tratamiento potencialmente curativa para el carcinoma de células escamosas del ano recurrente. Cuando están involucradas vísceras pélvicas, tejidos blandos y huesos adyacentes, puede ser necesaria una exenteración pélvica con una escisión perineal amplia para asegurar márgenes quirúrgicos claros y aumentar la probabilidad de supervivencia a largo plazo.OBJETIVO:Informar sobre los resultados oncológicos, de morbilidad y de calidad de vida de la exenteración pélvica por carcinoma anal de células escamosas.DISEÑO:Estudio de cohortes con análisis retrospectivo de datos recogidos prospectivamente.ENTORNO CLINICO:Este estudio se realizó en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos que se sometieron a exenteración pélvica por carcinoma anal de células escamosas entre 1994 y 2022.PRINCIPALES MEDIDAS DE VALORACIÓN:Supervivencia global y libre de recidiva local, tasas de complicaciones intraoperatorias y posoperatorias, tasa de resección R0 y resultados de calidad de vida a largo plazo.RESULTADOS:De 958 pacientes que se sometieron a exenteración pélvica, 66 (6,9%) tenían carcinoma anal de células escamosas. 32 pacientes (48,5%) eran varones y la mediana de edad fue de 57 años (rango 31-79). 10 pacientes (15%) tenían carcinoma anal primario de células escamosas, 49 (74%) tenían un tumor recurrente y 7 (11%) tenían una segunda recurrencia. 22 (33%) y 16 pacientes (24%) tuvieron una complicación mayor y regreso no planificado al quirófano, respectivamente. De los 62 pacientes que se sometieron a una exenteración pélvica con intención curativa, 50 (81%) tuvieron una resección R0, las tasas de supervivencia global y libre de recidiva local a los 5 años fueron del 41% y el 37%, respectivamente. La resección R0 se asoció con una mayor supervivencia general a los 5 años (50% frente a 8%, p < 0,001). Las puntuaciones del componente de salud mental y varios dominios de calidad de vida individuales presentaron trayectorias mejoradas después de la operación (todos los valores de p < 0,05).LIMITACIONES:La generalización de los hallazgos fuera de los centros especializados en exenteración pélvica puede ser limitada.CONCLUSIONES:Los resultados de morbilidad, supervivencia a largo plazo y calidad de vida después de la EP para el carcinoma anal de células escamosas son comparables a los resultados publicados de la exenteración pélvica para otros tipos de tumores. (Traducción-Dr. Ingrid Melo ).