Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.

Risk Factors for Severe Postoperative Complications after Oncologic Right Colectomy: Unicenter Analysis.

Background and Objectives: This study aimed to investigate the potential risk factors for severe postoperative complications after oncologic right colectomy. Materials and Methods: All consecutive patients with right colon cancer who underwent right colectomy in our department between 2016 and 2021 were retrospectively included in this study. The Clavien-Dindo grading system was used to evaluate postoperative complications. Univariate and multivariate logistic regression analyses were used to investigate risk factors for postoperative severe complications. Results: Of the 144 patients, there were 69 males and 75 females, with a median age of 69 (IQR 60-78). Postoperative morbidity and mortality rates were 41.7% (60 patients) and 11.1% (16 patients), respectively. The anastomotic leak rate was 5.3% (7 patients). Severe postoperative complications (Clavien-Dindo grades III-V) were present in 20 patients (13.9%). Univariate analysis showed the following as risk factors for postoperative severe complications: Charlson score, lack of mechanical bowel preparation, level of preoperative proteins, blood transfusions, and degree of urgency (elective/emergency right colectomy). In the logistic binary regression, the Charlson score (OR = 1.931, 95% CI = 1.077-3.463, p = 0.025) and preoperative protein level (OR = 0.049, 95% CI = 0.006-0.433, p = 0.007) were found to be independent risk factors for postoperative severe complications. Conclusions: Severe complications after oncologic right colectomy are associated with a low preoperative protein level and a higher Charlson comorbidity index.

Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis.

BACKGROUND & AIMS: Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. METHODS: We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. RESULTS: Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). CONCLUSIONS: We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide. ClinicalTrials.gov number: NCT03075618.

Clinical features of hypertriglyceridemia-induced acute pancreatitis in an international, multicenter, prospective cohort (APPRENTICE consortium).

BACKGROUND: The clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are not well-established. OBJECTIVE: To evaluate the clinical characteristics of HTG-AP in an international, multicenter prospective cohort. METHODS: Data collection was conducted prospectively through APPRENTICE between 2015 and 2018. HTG-AP was defined as serum TG levels >500 mg/dl in the absence of other common etiologies of AP. Three multivariate logistic regression models were performed to assess whether HTG-AP is associated with SIRS positive status, ICU admission and/or moderately-severe/severe AP. RESULTS: 1,478 patients were included in the study; 69 subjects (4.7%) were diagnosed with HTG-AP. HTG-AP patients were more likely to be younger (mean 40 vs 50 years; p < 0.001), male (67% vs 52%; p = 0.018), and with a higher BMI (mean 30.4 vs 27.5 kg/m2; p = 0.0002). HTG-AP subjects reported more frequent active alcohol use (71% vs 49%; p < 0.001), and diabetes mellitus (59% vs 15%; p < 0.001). None of the above risk factors/variables was found to be independently associated with SIRS positive status, ICU admission, or severity in the multivariate logistic regression models. These results were similar when including only the 785 subjects with TG levels measured within 48 h from admission. CONCLUSION: HTG-AP was found to be the 4th most common etiology of AP. HTG-AP patients had distinct baseline characteristics, but their clinical outcomes were similar compared to other etiologies of AP.

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

A pancreatic adenocarcinoma mimicking hepatoid carcinoma of uncertain histogenesis: A case report and literature review.

In rare cases, metastatic adenocarcinomas of different origin may exhibit the features of hepatoid carcinoma (HC), a rare malignant epithelial tumor, most commonly occurring in the ovaries and stomach, as well as in the pancreas and biliary ducts. A case of a 72-year-old female patient who developed a highly aggressive, poorly differentiated pancreatic ductal adenocarcinoma with peritoneal carcinomatosis, demonstrating hepatoid differentiation upon conventional hematoxylin and eosin staining is reported in the present study. The patient presented with severe abdominal pain, and the radiological investigations performed revealed ovarian and hepatic tumor masses and peritoneal lesions, which were surgically removed. The gross examination of the peritoneum and omentum revealed multiple solid, firm, grey-white nodules, diffusely infiltrating the adipose tissue. The microscopic examination revealed a malignant epithelial proliferation, composed of polygonal cells with abundant eosinophilic cytoplasm and irregular, pleomorphic nuclei. Certain cells presented with intracytoplasmic mucus inclusions, raising suspicion of a HC with an uncertain histogenesis. Immunohistochemical staining was performed, and the tumor cells were found to be positive for cytokeratin (CK)7, CK18 and mucin 5AC, whereas negative staining for CK20, caudal-type homeobox transcription factor 2, α-fetoprotein, paired box gene 8, GATA-binding protein 3 and Wilms tumor 1 were documented. Thus, the diagnosis of metastatic pancreatic adenocarcinoma was established. The main aim of the present study was to provide further knowledge concerning poorly differentiated metastatic adenocarcinoma resembling HC, emphasizing the histopathological and immunohistochemical features of these malignant lesions and raising awareness of the diagnostic difficulties that may arise, as well as the importance of the use immunohistochemistry in differentiating carcinomas of uncertain histogenesis.

Obesity and alcoholic etiology as risk factors for multisystem organ failure in acute pancreatitis: Multinational study.

BACKGROUND: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. OBJECTIVE: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. METHODS: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. RESULTS: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). CONCLUSION: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.

B1 versus B2 Dukes stage rectal cancer: prospective evaluation of 87 patients in a single institution and quest for re-evaluation of the current protocol.

BACKGROUND/AIMS: Current protocols indicate surgery as single modality of therapy for B1 stage rectal cancer and surgery with adjuvant therapy for B2 stage. The aim of our study was to analyze the five-year survival rate for patients with surgically treated B1 and B2 rectal cancer and to assess the impact of adjuvant therapy on overall survival. METHODOLOGY: Our epidemiological clinical study was based on a prospective analysis of 87 cases of B1 (n=32) and B2 (n=55) rectal cancers operated between 2000 and 2003. Survival evaluation was done through a prospective cohort followup study. RESULTS: There were 33 female and 54 males with a median age of 60 years (IQR 39-74). Tumor location was low rectum for 23 patients (26.4%), medium rectum for 30 patients (34.5%) and high rectum at 34 patients (37.9%). We performed Miles operation in 42 cases, Dixon resection in 26 cases and Hartmann operation in 18 patients. There was no difference in the number and type of postoperative complications between groups. There were no local recurrences in the B1 stage group but 7 cases (12.7%) in the B2 stage group. Distant metastases were recorded in 8 patients (25%) in the B1 group and 2 patients (3.6%) in the B2 group. The survival rate at 5 years (S5) was better for the B2 stage S5=69.9% than B1 stage S5=53.5% (p=0.001). CONCLUSIONS: Patients with B1 stage rectal cancer might benefit from adjuvant/neoadjuvant therapy.

Abdominal Compartment Syndrome in Acute Pancreatitis: A Narrative Review.

Abdominal compartment syndrome (ACS) represents a severe complication of acute pancreatitis (AP), resulting from an acute and sustained increase in abdominal pressure >20 mmHg, in association with new organ dysfunction. The harmful effect of high intra-abdominal pressure on regional and global perfusion results in significant multiple organ failure and is associated with increased morbidity and mortality. There are several deleterious consequences of elevated intra-abdominal pressure on end-organ function, including respiratory, cardiovascular, gastrointestinal, neurologic, and renal effects. It is estimated that about 15% of patients with severe AP develop intra-abdominal hypertension or ACS, with a mortality rate around 50%. The treatment of abdominal compartment syndrome in acute pancreatitis begins with medical intervention and percutaneous drainage, where possible. Abdominal compartment syndrome unresponsive to conservatory treatment requires immediate surgical decompression, along with vacuum-assisted closure therapy techniques, followed by early abdominal fascia closure.

Synchronous biliary gallstones and colorectal cancer: A single center analysis.

Gallstones and colorectal cancer (CRC) are two common disorders that may develop simultaneously. In such situations, there is a significant chance of missing one of the conditions due to the primary clinical presentation. Late detection, diagnosis and treatment can be especially problematic in the case of unrecognized CRC. In the present study, the medical charts were retrospectively reviewed for all consecutive patients who were treated in the Second Department of Surgery, University Emergency Hospital Bucharest (Romania) between February 2015 and December 2017 following a diagnosis of CRC and/or biliary stones. There were 203 patients with CRC, 433 with biliary gallstones and 19 patients with both conditions. There were 125 men (61.6%) in the CRC group and 138 men (31.9%) in the gallstone group. The average age was 54.1±15.9 years in the gallstone group and 66.1±11.6 years in the CRC group. Obesity was observed in 96 patients (22.2%) with gallstones and in 14 (6.9%) patients in the CRC group. In the CRC group, 80 patients had medical comorbidities (39.4%), while in the gallstone group 126 patients (29.1%) had medical comorbidities. Bivariate analysis comparing gallstone only vs. gallstone and CRC identified age (P=0.001), male sex (P=0.001) and thyroid disease (P=0.001) as significant factors associated with synchronous diagnosis. The multivariable logistic regression of factors predicting CRC in patients with gallstones identified age (OR, 1.06; 95% CI, 1.023-1.105; P=0.002) and thyroid diseases (OR, 11.15; 95% CI, 2.532-49.06; P=0.001) as independent factors. There were significant differences regarding the location of the tumor between the CRC-only group and the gallstone and CRC group (P=0.001): Rectum (39.7 vs. 5.3%), left colon (26.6 vs. 21.1%), transverse colon (13 vs. 26.3%) and right colon (20.7 vs. 47.4%). The study concluded that, in patients with gallstones, age and thyroid conditions were significantly associated with CRC. Patients with a synchronous diagnosis of gallstones and CRC had significantly more right-sided CRC compared with regular CRC.

The Impact of Postoperative Complications on Survival after Simultaneous Resection of Colorectal Cancer and Liver Metastases.

BACKGROUND: The aim of this study was to investigate the impact of postoperative complications on the long-term outcomes of patients who had undergone simultaneous resection (SR) of colorectal cancer and synchronous liver metastases (SCLMs). METHODS: We conducted a single-institution survival cohort study in patients with SR, collecting clinical, pathological, and postoperative complication data. The impact of these variables on overall survival (OS) and disease-free survival (DFS) was compared by log rank test. Multivariate Cox regression analysis identified independent prognostic factors. RESULTS: Out of 243 patients, 122 (50.2%) developed postoperative complications: 54 (22.2%) major complications (Clavien-Dindo grade III-V), 86 (35.3%) septic complications, 59 (24.2%) hepatic complications. Median comprehensive complication index (CCI) was 8.70. Twelve (4.9%) patients died postoperatively. The 3- and 5-year OS and DFS rates were 60.7%, 39.5% and 28%, 21.5%, respectively. Neither overall postoperative complications nor major and septic complications or CCI had a significant impact on OS or DFS. Multivariate analysis identified the N2 stage as an independent prognostic of poor OS, while N2 stage and four or more SCLMs were independent predictors for poor DFS. CONCLUSION: N2 stage and four or more SCLMs impacted OS and/or DFS, while CCI, presence, type, or grade of postoperative complications had no significant impact on long-term outcomes.

Prognostic Value of Lymph Node Ratio in Patients with Resected Synchronous Colorectal Liver Metastases and Less Than 12 Examined Lymph Nodes.

BACKGROUND: Recent studies suggest that lymph node ratio (LNR) has significantly better prognostic power than N-status in patients with colorectal cancer, in particular when the number of evaluated lymph nodes (LNs) was insufficient. The aim of this study was to assess the prognostic value of LNR in patients with resected synchronous colorectal liver metastases (SCLMs) and less than 12 examined LNs. METHODS: A prospectively maintained database of patients with resected SCLMs was queried for patients with less than 12 LNs evaluated at the time of surgery. X-tile software was used to determine the LNR cutoff value able to divide the patients in two subgroups with distinct prognosis. Overall survival (OS) and disease-free survival (DFS) rates were compared by log-rank test. A multivariate Cox regression analysis identified independent prognostic factors. RESULTS: A cutoff LNR value of 0.22 divided patients into Low-LNR group (35 patients) and High-LNR group (36 patients). Both OS and DFS rates were significantly higher in Low-LNR group than those in High-LNR group. Independent predictors of poor OS were High-LNR (HR: 2.841, 95% CI: 1.480-5.453, p value = 0.002), bilobar SCLMs (HR: 2.253, 95% CI: 1.144-4.437, p value = 0.019) and lack of adjuvant chemotherapy (HR: 2.702, 95% CI: 1.448-5.043, p value = 0.002), while the only independent predictor of poor DFS was High-LNR (HR: 2.531, 95% CI: 1.259-5.090, p value = 0.009). CONCLUSIONS: LNR > 0.22 was independently associated with poor OS and DFS in patients with resected SCLMs and less than 12 evaluated LNs.

Updates of Risk Factors for Anastomotic Leakage after Colorectal Surgery.

Anastomotic leakage is a potentially severe complication occurring after colorectal surgery and can lead to increased morbidity and mortality, permanent stoma formation, and cancer recurrence. Multiple risk factors for anastomotic leak have been identified, and these can allow for better prevention and an earlier diagnosis of this significant complication. There are nonmodifiable factors such as male gender, comorbidities and distance of tumor from anal verge, and modifiable risk factors, including smoking and alcohol consumption, obesity, preoperative radiotherapy and preoperative use of steroids or non-steroidal anti-inflammatory drugs. Perioperative blood transfusion was shown to be an important risk factor for anastomotic failure. Recent studies on the laparoscopic approach in colorectal surgery found no statistical difference in anastomotic leakage rate compared with open surgery. A diverting stoma at the time of primary surgery does not appear to reduce the leak rate but may reduce its clinical consequences and the need for additional surgery if anastomotic leakage does occur. It is still debatable if preoperative bowel preparation should be used, especially for left colon and rectal resections, but studies have shown similar incidence of postoperative leak rate.

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected.

BACKGROUND: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. OBJECTIVE: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. METHODS: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. RESULTS: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality. CONCLUSION: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.

Incidence and risk factors of oral feeding intolerance in acute pancreatitis: Results from an international, multicenter, prospective cohort study.

BACKGROUND: Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. OBJECTIVE: We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. METHODS: Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. RESULTS: Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance. CONCLUSION: Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology.

Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts.

OBJECTIVES: Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. METHODS: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). RESULTS: The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. CONCLUSIONS: The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

A rare case of clear-cell carcinoid of appendix.

The carcinoids are the most frequent type of tumors arising from the appendix. In the majority of cases, these tumors are asymptomatic and usually are discovered after appendectomy. Definitive diagnosis relies on pathological examination of the resected appendix, size of the tumor being critical for the further management. Clear-cell change in neuroendocrine tumors (NETs) has rarely been described in the appendix. We choose to present a clear-cell carcinoid subtype of appendiceal NET to raise awareness on this potentially curable and rare condition that can be overlooked. We highlight the importance of the pathological exam and the morphological and immunohistochemical behavior of the tumor in confirming the diagnosis and aiding in the treatment decision making. Also, important entities should be considered in the process of differential diagnosis such as goblet-cell carcinoid or renal-cell÷ovarian carcinoma.