Severity and outcome of a first episode of idiopathic acute pancreatitis is not more severe than pancreatitis of other etiologies.

BACKGROUND: With respect to severity and outcome of an index episode of idiopathic acute pancreatitis the current literature reports conflicting retrospective results. One reason might be the retrospective study design precluding in depth analysis resulting in mixed etiologies and combination of index episode versus recurrent idiopathic acute pancreatitis. METHODS: In this retrospective monocentric cohort study, we retrieved all patients with a first acute pancreatitis episode treated between 2005 and 2021 at the LMU University Hospital from our clinical information system based on the respective ICD-10 codes. In an initial sample of 1390 presumed idiopathic pancreatitis patients we identified 68 confirmed idiopathic acute pancreatitis patients and compared those to 75 first-time alcohol-induced acute pancreatitis patients and 390 first-time biliary-induced acute pancreatitis patients. Clinical outcome (severity, SIRS, mortality, and re-admission rate) was set as outcome measures. Multinomial logistic regression analysis was performed. RESULTS: In alcohol-induced acute pancreatitis moderate and severe courses occur significantly more often when compared to idiopathic acute pancreatitis (17.33 % vs. 10.29 %; multinomial logistic regression p = 0.0021). There were no significant differences in mortality between first-time alcoholic, idiopathic and biliary pancreatitis (p = 0.6328). Patients with idiopathic acute pancreatitis had significantly more hospital readmissions (within 30 days) compared to alcohol-induced pancreatitis patients (p = 0.0284). CONCLUSION: In the context of a first episode of acute pancreatitis, idiopathic acute pancreatitis remains a challenging diagnosis posing an increased risk of recurrence, but not an increased risk for a more severe disease course.

Tigecycline causes loss of cell viability mediated by mitochondrial OXPHOS and RAC1 in hepatocellular carcinoma cells.

BACKGROUND: Despite recent advances in locoregional, systemic, and novel checkpoint inhibitor treatment, hepatocellular carcinoma (HCC) is still associated with poor prognosis. The feasibility of potentially curative liver resection (LR) and transplantation (LT) is limited by the underlying liver disease and a shortage of organ donors. Especially after LR, high recurrence rates present a problem and circulating tumor cells are a major cause of extrahepatic recurrence. Tigecycline, a commonly used glycylcycline antibiotic, has been shown to have antitumorigenic effects and could be used as a perioperative and adjuvant therapeutic strategy to target circulating tumor cells. We aimed to investigate the effect of tigecycline on HCC cell lines and its mechanisms of action. METHODS: Huh7, HepG2, Hep3B, and immortalized hepatocytes underwent incubation with clinically relevant tigecycline concentrations, and the influence on proliferation, migration, and invasion was assessed in two- and three-dimensional in vitro assays, respectively. Bioinformatic analysis was used to identify specific targets of tigecycline. The expression of RAC1 was detected using western blot, RT-PCR and RNA sequencing. ELISA and flow cytometry were utilized to measure reactive oxygen species (ROS) generation upon tigecycline treatment and flow cytometry to detect alterations in cell cycle. Changes in mitochondrial function were detected via seahorse analysis. RNA sequencing was performed to examine involved pathways. RESULTS: Tigecycline treatment resulted in a significant reduction of mitochondrial function with concomitantly preserved mitochondrial size, which preceded the observed decrease in HCC cell viability. The sensitivity of HCC cells to tigecycline treatment was higher than that of immortalized non-cancerous THLE-2 hepatocytes. Tigecycline inhibited both migratory and invasive properties. Tigecycline application led to an increase of detected ROS and an S-phase cell cycle arrest. Bioinformatic analysis identified RAC1 as a likely target for tigecycline and the expression of this molecule was increased in HCC cells as a result of tigecycline treatment. CONCLUSION: Our study provides evidence for the antiproliferative effect of tigecycline in HCC. We show for the first time that this effect, likely to be mediated by reduced mitochondrial function, is associated with increased expression of RAC1. The reported effects of tigecycline with clinically relevant and achievable doses on HCC cells lay the groundwork for a conceivable use of this agent in cancer treatment.

Preoperative ultrasound elastography for postoperative pancreatic fistula prediction after pancreatoduodenectomy: A prospective study.

BACKGROUND: Postoperative pancreatic fistulas are the most frequent major complications after pancreatoduodenectomy. The soft pancreatic texture is a critical, independent risk factor for postoperative pancreatic fistulas after pancreatoduodenectomy. The current gold standard for postoperative pancreatic fistula risk evaluation consists of the surgeon's intraoperative palpation of the pancreatic texture and, thus, lacks objectivity. In this prospective study, we used ultrasound-based shear-wave elastography, image data analysis, and a fistula risk score calculator to correlate the stiffness of pancreatic tissue with the occurrence of clinically relevant postoperative pancreatic fistulas. METHODS: We included 100 patients with pancreatic pathologies (71% pancreatic ductal adenocarcinoma) and 100 healthy individuals who were preoperatively assessed via real-time tissue ultrasound-based shear-wave elastography on a Philips EPIQ 7 ultrasound device and had pancreatic parenchyma histologically evaluated with manually stained images. RESULTS: We found a significant difference in the mean elasticity between the soft (1.22 m/s) and the hard pancreas group (2.10 m/s; P < .0001). The mean elasticity significantly correlated with the pancreatic fibrosis rate and the appearance of a postoperative pancreatic fistula after pancreatoduodenectomy. Low elasticity (≤1.2 m/s, mean) correlated with soft and high elasticity (>2.0 m/s, mean) with hard pancreatic parenchyma, as assessed by pathologic evaluation. Multivariate analysis revealed a mean elasticity of <1.3 m/s as a significant cut-off predictor for clinically relevant postoperative pancreatic fistulas (P = .003; Youden-Index = 0.6945). CONCLUSION: Preoperative ultrasound-based shear-wave elastography is a feasible and objective clinical diagnostic modality in evaluating pancreatic tissue stiffness. A mean pancreatic elasticity of <1.3 m/s was a significant independent risk predictor of clinically relevant postoperative pancreatic fistulas after pancreatoduodenectomy.

Severity of Gallstone-, Sludge-, or Microlithiasis-Induced Pancreatitis-All of the Same?

BACKGROUND/AIM: Severity of microlithiasis- and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition. MATERIALS AND METHODS: In this retrospective cohort study, 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge, and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function, and endosonography/endoscopic retrograde cholangiopancreatography results using one-way analysis of variance and χ 2 test. Multinomial logistic regression analysis was performed to correct for bias. RESULTS: Microlithiasis- and sludge-induced pancreatitis, classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis ( P = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis ( P = 0.36). The likelihood of detecting biliary disease on endosonography resulting in bile duct clearance was highest on the day of admission and day 1, respectively. CONCLUSIONS: Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis.

Diagnostic and Therapeutic Management of Early Colorectal Cancer.

Background: Early colorectal cancer (eCRC) is defined as cancer that does not cross the submucosal layer of the colon or rectum, including carcinoma in situ (pTis), pT1a, and pT1b. Early carcinomas differ in their prognosis depending on the risk profile. The differentiation between low and high risk is essential. The low-risk group includes R0-resected, well (G1) or moderately (G2) differentiated tumors without lymphatic vessel invasion (L0), without blood vessel invasion (V0) and a tumor size ≤3 cm. In this constellation, the estimated risk of lymph node metastasis is around 1% or below. The high-risk group includes tumors with incomplete resection (Rx), poor (G3) or undifferentiated (G4) carcinomas, and/or lymphatic and blood vessel invasion (L1) and size ≥3 cm. In a "high-risk" situation, there is a risk for lymph node metastasis of up to 23%. Summary: The incidence of eCRC is rising with a rate of 10% in all endoscopically removed lesions during colonoscopy. For a correct histological evaluation, all suspected lesions should be completely resected. In case of a pT1 lesion in the rectum, pelvic magnetic resonance imaging should be performed to evaluate for suspicious lymph nodes. The therapeutic approach for eCRC is based on histological assessment and ranges from endoscopic resection to radical oncological surgery. The advantages, disadvantages, and associated risks of the individual treatment strategy need to be carefully discussed on a tumor board and with the patient. Key Messages: Treatment options for early colorectal cancer depend on the histological assessment. Poorly differentiated carcinomas, a Kudo ≥ SM2 classified lesion, and a Haggitt level 4 always represent a "high-risk" situation. It should also be mentioned that in rectal cancer, local surgical tumor excision (full-wall excision) is also sufficient for pT1 carcinomas with a "low-risk" constellation (G1/G2; L0, size <3 cm) and an R0 resection.