Colon Involvement in Necrotizing Pancreatitis: Incidence, Risk Factors, and Outcomes.

OBJECTIVE: To investigate the incidence, risk factors, and outcomes of colon involvement in patients with necrotizing pancreatitis. SUMMARY/BACKGROUND DATA: Necrotizing pancreatitis is characterized by a profound inflammatory response with local and systemic implications. Mesocolic involvement can compromise colonic blood supply leading to ischemic complications; however, few data exist regarding this problem. We hypothesized that the development of colon involvement in necrotizing pancreatitis (NP) negatively affects morbidity and mortality. METHODS: Six hundred forty-seven NP patients treated between 2005 and 2017 were retrospectively reviewed to identify patients with colon complications, including ischemia, perforation, fistula, stricture/obstruction, and fulminant Clostridium difficile colitis. Clinical characteristics were analyzed to identify risk factors and effect of colon involvement on morbidity and mortality. RESULTS: Colon involvement was seen in 11% (69/647) of NP patients. Ischemia was the most common pathology (n = 29) followed by perforation (n = 18), fistula (n = 12), inflammatory stricture (n = 7), and fulminant C difficile colitis (n = 3). Statistically significant risk factors for developing colon pathology include tobacco use (odds ratio (OR), 2.0; 95% confidence interval (CI), 1.2-3.4, P = 0.009), coronary artery disease (OR, 1.9; 95% CI, 1.1-3.7; P = 0.04), and respiratory failure (OR, 4.7; 95% CI, 1.1-26.3; P = 0.049). When compared with patients without colon involvement, NP patients with colon involvement had significantly increased overall morbidity (86% vs 96%, P = 0.03) and mortality (8% vs 19%, P = 0.002). CONCLUSION: Colon involvement in necrotizing pancreatitis is common; clinical deterioration should prompt its evaluation. Risk factors include tobacco use, coronary artery disease, and respiratory failure. Colon involvement in necrotizing pancreatitis is associated with substantial morbidity and mortality.

Pancreatic Adenocarcinoma Causing Necrotizing Pancreatitis: Not as Rare as You Think?

BACKGROUND: Necrotizing pancreatitis (NP) presents a unique clinical challenge because of its complex and lengthy disease course. Pancreatic necrosis occurs in 10%-20% of acute pancreatitis cases and may result from any etiology. Scattered reports describe pancreatic tumors causing NP; however, the relationship between these disease processes is not clear. We have treated patients whose NP was caused by pancreatic ductal adenocarcinoma (PDAC) and therefore sought to clarify the clinical outcomes of these patients. METHODS: Patients treated between 2005 and 2018 for NP caused by PDAC were identified. The relationship between NP and PDAC was examined, and the clinical courses of both disease processes were evaluated. RESULTS: Among 647 patients treated for NP, seven patients (1.1%) had PDAC and NP. The mean age at NP diagnosis was 60.6 y (range, 49-66). Two patients had postprocedural pancreatitis after cancer diagnosis, and the remaining five patients had NP caused by PDAC. Median duration between diagnoses of NP and PDAC was 5.6 mo (range, 3.5-21.8). For PDAC treatment, four patients received chemotherapy alone, one received palliative radiation therapy, and one died without oncologic management. One patient underwent operative resection of PDAC. Median survival was 12.7 mo (range, 0.4-49.9). CONCLUSIONS: PDAC may be a more common cause of NP than previously considered and should be considered in patients with NP of appropriate age in whom etiology is otherwise unclear. Prompt diagnosis facilitates optimal treatment in this challenging clinical situation.

Disconnected Pancreatic Duct Syndrome: Spectrum of Operative Management.

BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) is common after necrotizing pancreatitis (NP). Surgical management may be by internal drainage or left (distal) pancreatectomy. Therapeutic decision-making must consider sinistral portal hypertension, parenchymal volume of disconnected pancreas, and timing relative to definitive management of pancreatic necrosis. The aim of this study is to evaluate outcomes after operative management for DPDS. METHODS: All patients with NP undergoing an operation for DPDS were included in the study (2005-2017). Perioperative outcomes and long-term durability were evaluated. RESULTS: Among 647 patients with NP, 299 (46%) had DPDS. Operative management was required in 202/299 (68%) patients with DPDS. Median follow-up was 30 mo (2-165). Definitive operative therapy included internal drainage (n = 111) or resection (n = 91). Time from NP diagnosis to operation was 126 d (20 d to 81 mo). Overall morbidity was 46%. Postoperative length of stay was 7 d (2-97). Readmission was required in 39 patients (19%). Mortality was 2%. Repeat pancreatic intervention was required in 23 patients (11%) at a median of 15 mo (1-98). Repeat pancreatectomy was performed in nine patients and the remaining 14 patients were managed with endoscopic therapy. CONCLUSIONS: DPDS is a common and challenging consequence of NP. Appropriate operation is durable in nearly 90% of patients.

Visceral artery pseudoaneurysm in necrotizing pancreatitis: incidence and outcomes.

Background: Visceral artery pseudoaneurysms (VA-PSA) occur in necrotizing pancreatitis; however, little is known about their natural history. This study sought to evaluate the incidence and outcomes of VA-PSA in a large cohort of patients with necrotizing pancreatitis. Methods: Data for patients with necrotizing pancreatitis who were treated between 2005 and 2017 at Indiana University Health University Hospital and who developed a VA-PSA were reviewed to assess incidence, presentation, treatment and outcomes. Results: Twenty-eight of 647 patients with necrotizing pancreatitis (4.3%) developed a VA-PSA between 2005 and 2017. The artery most commonly involved was the splenic artery (36%), followed by the gastroduodenal artery (24%). The most common presenting symptom was bloody drain output (32%), followed by incidental computed tomographic findings (21%). The median time from onset of necrotizing pancreatitis to diagnosis of a VA-PSA was 63.5 days (range 1-957 d). Twenty-five of the 28 patients who developed VA-PSA (89%) were successfully treated with percutaneous angioembolization. Three patients (11%) required surgery: 1 patient rebled following embolization and required operative management, and 2 underwent upfront operative management. The mortality rate attributable to hemorrhage from a VA-PSA in the setting of necrotizing pancreatitis was 14% (4 of 28 patients). Conclusion: In this study, VA-PSA occurred in 4.3% of patients with necrotizing pancreatitis. Percutaneous angioembolization effectively treated most cases; however, mortality from VA-PSA was high (14%). A high degree of clinical suspicion remains critical for early diagnosis of this potentially fatal problem.

Contexte: Les faux anévrismes des artères viscérales (FAAV) surviennent en présence d'une pancréatite nécrosante; on en sait cependant peu sur leur histoire naturelle. L'objectif de l'étude était d'évaluer l'incidence et les issues des FAAV dans une grande cohorte de patients atteints de pancréatite nécrosante. Méthodes: Nous avons examiné les données des patients atteints de pancréatite nécrosante traités entre 2005 et 2017 à l'Hôpital universitaire de l'Université de l'Indiana qui ont fait un FAAV afin d'évaluer l'incidence, les premiers signes, le traitement et les issues de cette affection. Résultats: Vingt-huit (4,3 %) des 647 patients atteints de pancréatite nécrosante inclus (2005­2017) ont fait un FAAV. L'artère la plus souvent touchée était l'artère splénique (36 %), suivie de l'artère gastroduodénale (24 %). Les premiers signes les plus courants étaient la présence de sang dans les liquides évacués par drainage (32 %), puis les résultats d'une tomodensitométrie effectuée pour une autre raison (21 %). Le délai médian entre l'apparition de la pancréatite nécrosante et le diagnostic de FAAV était de 63,5 jours (intervalle : 1 à 957 jours). Vingt-cinq des 28 patients ayant fait un FAAV (89 %) ont été traités avec succès par angioembolisation percutanée. Trois patients (11 %) ont dû être opérés : 2 dès le début, et le troisième parce qu'il a recommencé à saigner après l'embolisation. Le taux de mortalité par hémorragie due à un FAAV chez les personnes atteintes d'une pancréatite nécrosante était de 14 % (4 patients sur 28). Conclusion: Dans cette étude, 4,3 % des patients atteints de pancréatite nécrosante ont connu un FAAV. L'angioembolisation percutanée s'est avérée efficace dans la plupart des cas; cependant, la mortalité associée aux FAAV était élevée (14 %). Il est crucial de faire preuve d'une grande suspicion clinique afin de diagnostiquer tôt cette affection potentiellement mortelle.

Total Pancreatectomy with Percutaneous Islet Autotransplant after Remote Islet Processing: A Viable Paradigm?

OBJECTIVES: Total pancreatectomy with islet autotransplant (TPIAT) is important therapy for select chronic pancreatitis (CP) patients. The specialized technique of islet isolation limits widespread TPIAT use. We hypothesized that remote islet isolation provides satisfactory islet yield and perioperative outcomes. METHODS: Retrospective review of TPIAT patients between 2020 and 2022. Islet isolation was performed off-site, with percutaneous intraportal islet autotransplant (IAT) completed the morning following pancreatectomy. Demographics and perioperative outcomes were analyzed. RESULTS: Fourteen patients underwent TPIAT; median age was 43 [interquartile range 12.5] years. Operation occurred 7.5 [14.8] years after pancreatitis diagnosis. The most common pancreatitis etiology was genetic (50%). All patients underwent preoperative endoscopic therapy; three underwent prior pancreatectomy. Operative time was 236 [51] minutes; subsequent percutaneous IAT time was 87 [35] minutes. The islet equivalent (IEQ)/kilogram (kg) yield was 3,456 [3,815] IEQ/kg. Nine patients had positive islet cultures. Two thromboembolic events and one bacteremia occurred. One perihepatic hematoma occurred after percutaneous portal venous access. Median postoperative length of stay was 14.5 days, and five patients (36%) were readmitted within 90 days. All patients were discharged home on insulin. No mortality occurred. CONCLUSION: Total pancreatectomy with remote islet isolation provides excellent islet yield for autotransplant and satisfactory perioperative outcomes.

Transduodenal Sphincteroplasty: A Visual Case Study.

BACKGROUND: Sphincter of Oddi dysfunction is a challenging and rare clinical entity resulting in pancreatobiliary pain and stasis of bile and pancreatic juice. This problem was classically treated with surgical therapy, but as classification of the disease has changed and newer methods of endoscopic evaluation and therapy have evolved, operative transduodenal sphincteroplasty is now generally reserved as a final therapeutic option for these patients. In this video and manuscript, we describe our approach to operative transduodenal sphincteroplasty in a patient with type I Sphincter of Oddi dysfunction. METHODS: A 50-year-old female with history of Roux-en-Y gastric bypass presented with episodic right-upper-quadrant and epigastric abdominal pain with associated documented elevations in liver chemistries. Preoperative cross-sectional imaging demonstrated dilation of her common bile duct. After multidisciplinary discussion, the decision was made to pursue operative transduodenal sphincteroplasty. RESULTS: All key operative steps of the transduodenal sphincteroplasty are demonstrated in the embedded video. Key operative steps include laparotomy, generous Kocher maneuver, and duodenotomy over the ampulla, allowing access for sequential biliary and pancreatic sphincterotomies and sphincteroplasties with absorbable suture. The duodenotomy and abdominal fascia are then closed. Our patient underwent sequential diet advancement and was discharged to home on postoperative day five. At clinic follow-up, pancreatobiliary-type pain had resolved. CONCLUSION: The embedded video demonstrates a case of operative transduodenal sphincteroplasty, which can provide durable results in appropriate patient populations.

Obesity Worsens Local and Systemic Complications of Necrotizing Pancreatitis and Prolongs Disease Course.

BACKGROUND: Obesity is epidemic in the USA. Limited data exist examining obesity's influence on necrotizing pancreatitis (NP) disease course. METHODS: Retrospective review of prospectively maintained database of 571 adult necrotizing pancreatitis patients treated between 2007 and 2018. Patients were grouped according to body mass index (BMI) at disease onset. Patient characteristics, necrotizing pancreatitis course, and outcomes were compared between non-obese (BMI < 30) and obese (BMI > 30) patients. RESULTS: Among 536 patients with BMI data available, 304 (57%) were obese (BMI > 30), and 232 (43%) were non-obese (BMI < 30). NP etiology in the obese group was more commonly biliary (55% versus 46%, p = 0.04) or secondary to hypertriglyceridemia (10% versus 2%, p < 0.001) and less commonly alcohol (17% versus 26%, p = 0.01). Obese patients had a higher incidence of baseline comorbid disease. The CT severity index was similar between groups though obese patients had a higher rate of > 50% pancreatic gland necrosis (27% versus 19%, p = 0.02). The rates of infected necrosis and organ failure were higher among obese patients. Percutaneous drainage was more common in obese patients. Time to first necrosis intervention was earlier with increasing BMI. NP disease duration was longer in obese patients. The overall mortality rate of non-obese and obese patients did not differ. However, mortality rate increased with increasing BMI. CONCLUSION: Necrotizing pancreatitis in obese patients is characterized by a prolonged disease course, a higher risk of organ failure, infected necrosis, and the need for early necrosis-related intervention. Mortality increases with increasing BMI.

Prospective Analysis of the Mechanisms Underlying Ineffective Deep Vein Thrombosis Prophylaxis in Necrotizing Pancreatitis.

BACKGROUND: Patients with necrotizing pancreatitis (NP) have the highest rate of venous thromboembolism (VTE) of any hospitalized patient (57%). We hypothesized that VTE prophylaxis might be inadequate in the setting of this profound inflammatory disease and that early detection of deep vein thrombosis would limit pulmonary embolism. STUDY DESIGN: All patients with NP treated at a single center between August 2018 and December 2019 were enrolled in prospective, weekly VTE screening, including 4-extremity duplex ultrasound. Routine chemoprophylaxis included low-molecular-weight or unfractionated heparin. Peak serum anti-factor Xa concentration was measured during weekly screening (goal prophylaxis 0.2 to 0.4 IU/mL). RESULTS: Eighty-five patients with NP underwent a total of 201 screening events (mean 2.4 per patient). VTE developed in 55 patients (65%), including splanchnic vein thrombosis in 41 patients (48%) and extremity deep vein thrombosis (eDVT) in 32 patients (38%). Extremity DVT was diagnosed a mean ± SD of 44 ± 30 days after NP onset. Symptomatic pulmonary embolism was prevented in all patients diagnosed with eDVT and no contraindication to anticoagulation (0 of 29). Prophylactic anti-factor Xa concentration was only achieved in 21% (12 of 57 screening events); no eDVTs developed in patients achieving prophylactic anti-factor Xa concentration. CONCLUSIONS: In patients with NP, identification of eDVT by screening ultrasound permits early treatment and prevents symptomatic pulmonary embolism. Fixed dosing of chemical prophylaxis is inadequate in most patients with NP and likely contributes to the mechanism of increased VTE in NP.

Lung biopsy in children's interstitial and diffuse lung disease: Does it alter management?

INTRODUCTION: Pediatric patients with acute life-threatening consequences of interstitial and diffuse lung disease are often treated with empiric systemic corticosteroids, immune modulators, and/or broad antibiotic therapy. Histological evaluation of lung tissue represents the final necessary step in diagnosis-however, a definitive diagnosis may still remain elusive and medical therapies may not be changed following biopsy. We hypothesized that lung biopsy from pediatric patients with children's interstitial and diffuse lung disease (chILD) without a defined lesion on computed tomography (CT) imaging would guide diagnosis, but not substantially alter clinical management. METHODS: After IRB approval, patients who underwent a lung biopsy at a single large children's hospital between 2013 and 2018 were retrospectively reviewed. Patients without a defined lesion were included. Demographics, length of stay, oxygen-requirements, steroid, unique number of immune modulators, and antibiotics prebiopsy and postbiopsy were reviewed. Nonparametric data were compared by the Mann Whitney U and Kruskal Wallace tests and expressed as median with interquartile range. Decision tree alterations were analyzed by t test. P < .05 was significant. RESULTS: Sixty-four patients underwent lung biopsy during the period. Nineteen (30%) did not have a defined lesion on CT scan, and were included. A significant difference was seen between prebiopsy, 2 weeks, and 2 months postbiopsy prednisone dosing (P = .03), while the number of unique immune modulators, antibiotics, type of oxygen support and FiO2 were not significantly different before or after obtaining biopsy results. Pathology results provided additional information in 12 of 19 (63%) patients which resulted in management changes. CONCLUSIONS: Lung biopsy in chILD may guide clinical management, especially influencing the management of steroid dosing. Although on aggregate the number of antibiotics, immune modulators, mode of oxygen support and FiO2 did not differ significantly before and after biopsy, the pathologic evaluation provided diagnostic information that led to a variety of changes in therapeutic management in greater than half of the population.

High Rates of Readmission in Necrotizing Pancreatitis: Natural History or Opportunity for Improvement?

BACKGROUND: Necrotizing pancreatitis (NP) is a complex and heterogeneous disease with a protracted disease course. Hospital readmission is extremely common; however, few data exist regarding the cause of readmission in NP. METHODS: A retrospective review of NP patients treated between 2005 and 2017 identified patients readmitted both locally and to our hospital. All patients with unplanned hospital readmissions were evaluated to determine the cause for readmission. Clinical and demographic factors of all patients were recorded. As appropriate, two independent group t tests and Pearson's correlation or Fisher's exact tests were performed to analyze the relationship between index admission clinical factors and readmission. p values of < 0.05 were accepted as statistically significant. RESULTS: Six hundred one NP patients were reviewed. Median age was 52 years (13-96). Median index admission length of stay was 19 days (2-176). The most common etiology was biliary (49.9%) followed by alcohol (20.0%). Unplanned readmission occurred in 432 patients (72%) accounting for a total of 971 unique readmissions (mean readmissions/patient, 2.3). The most common readmission indications were symptomatic necrosis requiring supportive care and/or intervention (31.2%), infected necrosis requiring antibiotics and/or intervention (26.6%), failure to thrive (9.7%), and non-necrosis infection (6.6%). Patients requiring readmission had increased incidence of index admission renal failure (21.3% vs. 14.2%, p = 0.05) and cardiovascular failure (12.5% vs. 4.7%, p = 0.01). DISCUSSION: Readmission in NP is extremely common. Significant portions of readmissions are a result of the disease natural history; however, a percentage of readmissions appear to be preventable. Patients with organ failure are at increased risk for unplanned readmission and will benefit from close follow-up.

Quantitation of Intra-peritoneal Ovarian Cancer Metastasis.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy in the United States. Mortality is due to diagnosis of 75% of women with late stage disease, when metastasis is already present. EOC is characterized by diffuse and widely disseminated intra-peritoneal metastasis. Cells shed from the primary tumor anchor in the mesothelium that lines the peritoneal cavity as well as in the omentum, resulting in multi-focal metastasis, often in the presence of peritoneal ascites. Efforts in our laboratory are directed at a more detailed understanding of factors that regulate EOC metastatic success. However, quantifying metastatic tumor burden represents a significant technical challenge due to the large number, small size and broad distribution of lesions throughout the peritoneum. Herein we describe a method for analysis of EOC metastasis using cells labeled with red fluorescent protein (RFP) coupled with in vivo multispectral imaging. Following intra-peritoneal injection of RFP-labelled tumor cells, mice are imaged weekly until time of sacrifice. At this time, the peritoneal cavity is surgically exposed and organs are imaged in situ. Dissected organs are then placed on a labeled transparent template and imaged ex vivo. Removal of tissue auto-fluorescence during image processing using multispectral unmixing enables accurate quantitation of relative tumor burden. This method has utility in a variety of applications including therapeutic studies to evaluate compounds that may inhibit metastasis and thereby improve overall survival.

Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival.