Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Design and optimization of nano-formulations for a novel colchicine derivative

Introduction: Chemotherapy is the most reliable approach to cancer treatment, but it is often associated with side effects due to anti-cancer compounds' toxicity and non-selectivity [1]. CCI- 001 is a novel colchicine derivative, computationally designed by modifying colchicine’s basic structure, that exploits the affinity with βIII-tubulin to impair the mitosis of cancer cells [1]. CCI- 001 showed lower general toxicity, increased selectivity and specificity [1]. Despite this, its applications are limited by low water solubility and poor tumor uptake. [1]. This may reduce CCI- 001 efficacy and produce undesirable side effects. To solve this issue, this contribution describes the design of new efficient transporters of CCI-001 (polymeric nanoparticles, NPs) to enhance target accumulation and reduce the off-target effects. Methods: CCI-001 was successfully loaded in core-shell pegylated NPs, using the nanoprecipitation method [2]. In detail, a poly-ε-caprolactone (PCL)-based polyurethane (NHSC2000) was solubilized in acetonitrile and precipitated in water containing a mix of phospholipids (L-α- phosphatidylglycerol, PG and 1,2 – Distearoyl- sn – glycerol – 3 – phosphoethanolamine – Poly (ethylene glycol), DSPE-PEG). In vitro efficacy of CCI-001 loaded- NPs was analyzed against 2D and 3D cultures (spheroids) of three cell lines: U87MG (glioblastoma multiforme), Mia-PaCa-2 (pancreatic adenocarcinoma) and OVCAR-3 (ovarian cancer). Results: NPs of small size (~170 nm), narrow size distribution (PDI<0.3), high stability in aqueous solution, and satisfying encapsulation efficiency (6 %) were obtained [3]. CCI-001-loaded NPs caused a significant decrease in the viability of each cell line tested. The maximum effect was exerted after 72h, at a concentration of 2,5 μM, where residual viabilities of 50%, 30%, and 26% were reached for 2D culture of U87MG, Mia-PaCa-2, and OVCAR-3, respectively (Figure 1a). NPs exhibited similar results on U-87 and Mia-PaCa-2 spheroids, while OVCAR-3 spheroids' viabilities are higher than the corresponding 2D culture (as shown in Figure 1b). Also, empty NPs did not elicit signs of toxicity on these cell lines, up to a concentration of 1 mg/ml. Conclusions: Overall, our results demonstrate that nano-formulations of CCI-001 can be obtained with satisfying loading efficacy without altering the anti-cancer effect of the drug, warranting their further investigation

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian and gastrointestinal peritoneal carcinomatosis: Results from a 7-year experience

Background: An increasing promising evidence and increasing long-term oncologic outcomes support the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as locoregional treatment for peritoneal carcinosis (PC) especially from ovarian and gastrointestinal tumors, but also for others cancers. Methods: A prospective monocentric study was performed in Papa Giovanni XXIII Hospital, Bergamo (Italy). Patients and tumor characteristics were analyzed. Overall survival (OS), disease free survival (DFS) and morbidity were analyzed with Kaplan-Meier curves and log-rank testing. Results: A total of 150 patients undergone CRS + HIPEC were analyzed from January 2011 to June 2017. The principal origins of PC were: gastric cancer (GC) (n=40), colon cancer (n=31), appendiceal cancer (AC) (n=18), ovarian cancer (OC) (n=49), others (n=12). Major morbidity [≥3 Common Terminology Criteria for Adverse Events (CTCAE)] and perioperative mortality rates were 38% and 2.7% respectively. Re-operation rate was 15.3%. Median OS is 9, 35, 47, 51, 82 months (29% 3-year OS; 27% 5-year OS; 48% 5-year OS; 40% 5-year OS; 67% 5-year OS respectively) in GC, colorectal cancer (CRC), OC, others tumors and AC respectively. Median DFS is 4, 14, 17, 19, 82 months (32% 3-year DFS; 22% 5-year DFS; 29% 5-year DFS; 11% 5-year DFS; 67% 5-year DFS respectively) in GC, CRC, others tumors, OC and AC respectively. Conclusions: A therapeutic approach that combined CRS + HIPEC could achieve long-term survival in selected groups of patients with PC from gastrointestinal, gynecological and others tumors with acceptable morbidity and mortality. A good expertise and a high volume of patients are necessary to manage PC and to further improve results

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135–15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359–5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138–5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184–5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598–9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090–6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286–5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912–7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138–0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143–0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990). Graphical abstract: [Figure not available: see fulltext.]

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis): The MANCTRA-1 international audit

Background/objectives: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines. Methods: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study. Categorical data were reported as percentages representing the proportion of all study patients or different and well-defined cohorts for each variable. Continuous data were expressed as mean and standard deviation. Differences between the compliance obtained in the four different subgroups were compared using the Mann-Whitney U, Student's t, ANOVA or Kruskal-Wallis tests for continuous data, and the Chi-square test or the Fisher's exact test for categorical data. Results: Complete data were available for 5275 patients. The most commonly discordant gaps between daily clinical practice and recommendations included the optimal timing for the index CT scan (6.1%, χ2 6.71, P&nbsp;=&nbsp;0.081), use of prophylactic antibiotics (44.2%, χ2 221.05, P&nbsp;&lt;&nbsp;0.00001), early enteral feeding (33.2%, χ2 11.51, P&nbsp;=&nbsp;0.009), and the implementation of early cholecystectomy strategies (29%, χ2 354.64, P&nbsp;&lt;&nbsp;0.00001), with wide variability based on the admitting speciality. Conclusions: The results of this study showed an overall poor compliance with evidence-based guidelines in the management of ABP, with wide variability based on the admitting speciality. Study protocol registered in ClinicalTrials.Gov (ID Number NCT04747990)