Role of preoperative sarcopenia in predicting postoperative complications and survival after pancreatoduodenectomy for pancreatic cancer.

AIM: The aim of this monocentric retrospective study was to investigate the relation between sarcopenia, postoperative complications and survival in patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC). MATERIAL OF STUDY: From a prospective collected database of 230 consecutive pancreatoduodenectomies (PD), data regarding patient's body composition, evaluated on diagnostic preoperative CT scans and defined as Skeletal Muscle Index (SMI) and Intramuscular Adipose Tissue Content (IMAC), postoperative complications and long-term outcomes were retrospectively analysed. Descriptive and survival analyses were performed. RESULTS: Sarcopenia was found in 66% of study population. The majority of patients who developed at least one postoperative complication was sarcopenic. However, sarcopenia did not statistically significantly relate with the development of postoperative complications. However, all pancreatic fistula C occurs in sarcopenic patients. Moreover, there was no significant difference in median Overall Survival (OS) and Disease Free Survival (DFS) between sarcopenic and nonsarcopenic patients (31 versus 31.8 months and 12.9 and 11.1 months respectively). DISCUSSION: Our results showed that sarcopenia was not related to short- and long-term outcomes in PDAC patients undergoing PD. However, the quantitative and qualitative radiological parameters are probably not enough to study the sarcopenia alone. CONCLUSIONS: The majority of early stage PDAC patients undergoing PD were sarcopenic. Cancer stage was a determinant factor of sarcopenia while BMI seems less important. In our study, sarcopenia was associated with postoperative complications and in particular with pancreatic fistula. Further studies will need to demonstrated that sarcopenia can be considered an objective measure of patient frailty and strongly associated with short- and long-term outcomes. KEY WORDS: Pancreatic ductal adenocarcinoma, Pancretoduodenectomy, Sarcopenia.

Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster?

The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists' role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.

Different Biliary Microbial Flora Influence Type of Complications after Pancreaticoduodenectomy: A Single Center Retrospective Analysis.

BACKGROUND: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD. METHODS: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF). RESULTS: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli, Klebsiella pneumoniæ and Enterococcus fæcalis (p < 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli, Klebsiella pneumoniæ, Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF (p < 0.001). Biliary culture positive for Escherichia coli, Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE (p < 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30-6.70); p < 0.01). CONCLUSIONS: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.

Efficient pancreatic cancer detection through personalized protein corona of gold nanoparticles.

Characterization of the personalized protein corona (PC) that forms around nanomaterials upon exposure to human plasma is emerging as powerful technology for early cancer detection. However, low material stability and interbatch variability have limited its clinical application so far. Here, we present a nanoparticle-enabled blood (NEB) test that uses 120 nm gold nanoparticles (NPs) as the accumulator of blood plasma proteins. In the test, the personalized PC of gold NPs is characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. As a paradigmatic case study, pancreatic ductal adenocarcinoma (PDAC) was chosen due to the lack of effective detection strategies that lead to poor survival rate after diagnosis (<1 year) and extremely low 5-years survival rate (15-20%). Densitometric analysis of 75 protein patterns (28 from healthy subjects and 47 from PDAC patients) allowed us to distinguish nononcological and PDAC patients with good sensitivity (78.6%) and specificity (85.3%). The gold NEB test is completely aligned to affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end users criteria stated by the World Health Organization for cancer screening and detection. Thus, it could be very useful in clinical practice at the first level of investigation to decide whether to carry out more invasive analyses or not.

The use of an implemented infection prevention bundle reduces the incidence of surgical site infections after colorectal surgery: a retrospective single center analysis.

BACKGROUND: Surgical-site infections (SSIs) represent the most common complications after colorectal surgery (CS). Role of preoperative administration of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP), alone or in combination, in the prevention of SSIs after CS is debated. Aim of this study was to assess the effect of the introduction of an Implemented Infection Prevention Bundle (IIPB) in preventing SSIs in CS. METHODS: A group of 251 patients (Group 1) who underwent CS receiving only preoperative intravenous antibiotic prophylaxis (IAP) was compared to a Group of 107 patients (Group 2) who also received the IIPB. The IIPB consisted of the combination of oral administrations of three doses of Rifaximin 400 mg and MBP the day before surgery and in the administration of a cleansing enema the day of the surgical procedure. RESULTS: At the univariate analysis, Group 2 showed significant lower rates of wound infection (WI) (2.8% vs. 9.9%; p = 0.021) and anastomotic leakage (AL) (2.8% vs. 14.7%; p = 0.001) with shorter hospital stay (5 vs. 6 days; p < 0.0001). The probability of postoperative AL was lower in Group 2; patients in this Group resulted protected from AL; a statistically significant Odds ratio of 0.16 (CI 0.05-0.55 p = 0.0034) was found. In diabetic patients, that were at higher risk of WI (OR 3.53, CI 1.49-8.35 p = 0.002), despite having any impact on anastomotic dehiscence, the use of IIPB significantly reduced the rate of WI (0% vs 28.1%; p = 0.01). CONCLUSION: The use of an IIPB significantly reduces rates of SSIs and post-operative hospital stay after CS.

Laparoscopic total mesorectal excision (L-TME) for rectal cancer surgery: does elective diverting ileostomy really protect? An observational retrospective cohort study.

AIMS: Elective diverting ileostomy may reduce consequences of anastomotic leakage after laparoscopic total mesorectal excision (L-TME); however, its safety is debated because of morbidity related to stoma creation and closure. We aimed to investigate the impact of diverting ileostomy on clinical behavior of anastomotic leakage and complications related to stoma itself. MATERIAL OF THE STUDY: We retrospectively evaluated 150 L-TMEs with (Group 1, 100 patients) or without (Group 2, 50 patients) elective ileostomy for rectal cancer. RESULTS: Overall anastomotic fistula rate was 26% without significant differences between the two groups (28% in the Group 1 and 22% in the Group 2, respectively). In all the series, NAD was significantly associated with higher risk of postoperative complications (OR=2.14, p=0.02). In Group 2, NAD particularly increased the risk of anastomotic fistula (OR=6.6, p=0.014). Instead, patients of Group 1 showed higher odd of post-operative complications (OR: 3.8; CI 95%: 1.8483-8.0492; p = 0.0003) and notably 79 (79%) developed complications related to the ileostomy itself (hydroelectrolytic, metabolic and peristomal skin disorders). Moreover, thirty-two (32%) ileostomies were never reversed; among the reversed patients, 27 (39.7%) developed at least one postoperative complication and in 9 (33.3%) cases an urgent re-intervention was needed. DISCUSSION: Diverting ileostomy may mitigate clinical behavior of anastomotic leakage after L-TME. However, there is non-negligible morbidity of stoma creation and closure. CONCLUSION: Diverting ileostomy should be selectively considered in higher risk patients as those who received NAD. KEY WORDS: Anastomotic leakage, Ileostomy, Rectal cancer.

A protein corona sensor array detects breast and prostate cancers.

Following exposure to human plasma (HP), nanoparticles (NPs) are coated with a biomolecular layer referred to as a protein corona. We recently revealed that characterizing the protein coronas of various NPs may provide a unique opportunity for cancer identification and discrimination. In other words, protein corona profiles of several NPs, when being analyzed using classifiers, would provide a unique "fingerprint" for each type of disease. Here, we probed the capacity of the protein corona for the identification and discrimination of breast and prostate cancer patients from healthy individuals. Using three lipid NP formulations with distinct physical-chemical properties as a cross-reactive sensor array and a supervised random forest classifier, we identified a set of proteins that showed a significant difference in cancer patients and control subjects. Our data show that many of the corona proteins with the highest discrimination ability between oncological patients and healthy individuals are related to cellular and molecular aspects of breast and prostate cancers.

Preoperative systemic inflammatory biomarkers and postoperative day 1 drain amylase value predict grade C pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Postoperative day 1-drains amylase (POD1-DA) values are commonly used to predict the risk of pancreatic fistula (PF) after pancreaticoduodenectomy (PD). Perioperative inflammatory biomarkers have been associated to higher risk of complications in different oncological surgeries. Aim of this study was to investigate the utility of the combination of preoperative inflammatory biomarkers (PIBs) with POD1-DA levels in predicting grade C PF. MATERIALS AND METHODS: From a prospective collected database of 317 consecutive pancreaticoduodenectomies, data regarding POD1-DA levels and PIBs as neutrophil-to-lymphocyte ratio (NRL), derived neutrophil-to-lymphocyte ratio (dNRL), platelet-to-lymphocyte ratio (PLR) were analyzed in 227 cases. P-values <0.05 were considered statistically significant. Receiver operating characteristic (ROC) curves defined the optimal thresholds for biomarkers and drains amylase values and their accuracy to predict PF. Furthermore, the Positive Predictive Value (PPV) was computed to evaluate the probability to develop PF combining PIBs and drains amylase values. Combination of drains amylase and different PIBs cut-offs were used to evaluate the risk of grade C PF. RESULTS: A POD1-DA level of 351 U/L significantly predicted PF (sensitivity 82.7%, specificity 76%, AUC 0.836; p < 0.001) with a PPV of 76.5% and a NPV of 82.6%.POD1-DA levels ≥807 U/L significantly predicted grade C PF (sensitivity 72.7%, specificity 64.4%, AUC 0.676; p = 0.004) with a PPV of 17.8% and a NPV of 95.6%.Notably, this last PPV increased from 17.8% to 89% when PIBs, at different cut-offs, were combined with POD1-DA at the value ≥ 807 U/L. CONCLUSION: PIBs significantly improve POD1-DA ability in predicting grade C PF after PD.

Personalized Graphene Oxide-Protein Corona in the Human Plasma of Pancreatic Cancer Patients.

The protein corona (PC) that forms around nanomaterials upon exposure to human biofluids (e.g., serum, plasma, cerebral spinal fluid etc.) is personalized, i.e., it depends on alterations of the human proteome as those occurring in several cancer types. This may relevant for early cancer detection when changes in concentration of typical biomarkers are often too low to be detected by blood tests. Among nanomaterials under development for in vitro diagnostic (IVD) testing, Graphene Oxide (GO) is regarded as one of the most promising ones due to its intrinsic properties and peculiar behavior in biological environments. While recent studies have explored the binding of single proteins to GO nanoflakes, unexplored variables (e.g., GO lateral size and protein concentration) leading to formation of GO-PC in human plasma (HP) have only marginally addressed so far. In this work, we studied the PC that forms around GO nanoflakes of different lateral sizes (100, 300, and 750 nm) upon exposure to HP at several dilution factors which extend over three orders of magnitude from 1 (i.e., undiluted HP) to 103. HP was collected from 20 subjects, half of them being healthy donors and half of them diagnosed with pancreatic ductal adenocarcinoma (PDAC) a lethal malignancy with poor prognosis and very low 5-year survival rate after diagnosis. By dynamic light scattering (DLS), electrophoretic light scattering (ELS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nano liquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments we show that the lateral size of GO has a minor impact, if any, on PC composition. On the other side, protein concentration strongly affects PC of GO nanoflakes. In particular, we were able to set dilution factor of HP in a way that maximizes the personalization of PC, i.e., the alteration in the protein profile of GO nanoflakes between cancer vs. non-cancer patients. We believe that this study shall contribute to a deeper understanding of the interactions among GO and HP, thus paving the way for the development of IVD tools to be used at every step of the patient pathway, from prognosis, screening, diagnosis to monitoring the progression of disease.

Role of drain amylase levels assay and routinary postoperative day 3 abdominal CT scan in prevention of complications and management of surgical drains after pancreaticoduodenectomy.

To asses drains amylase (DA) cut-offs for the risk of clinically relevant postoperative pancreatic fistula (POPF) and define the optimal timing of drains removal based on daily DA assay and abdominal CT scan finding after pancreatoduodenectomy (PD). Different algorithms able to identify patients at higher risk of POPF and to assess the optimal time for drains removal after PD have been proposed. The most accurate DA cut-offs in the assessment of the risk of clinically relevant POPF were retrospectively identified. Data from a prospective trial for optimal timing of drains removal were analyzed. Then, to validate the cut-offs identified in the first phase, they were applied to the patients enrolled in the prospective trial. Patients with POD1 DA ≥ 666 U/L were at higher risk of clinically relevant POPF (p 0.0001). POD3 DA value ≥ 252 U/L predicted 88% of clinical relevant fistulas. POD3 DA level ≥ 207 U/L was able to predict 68% of biliary fistulas. Patients with abdominal collection ≥ 5 cm, showed a significantly higher rate (60% vs. 23%, p < 0.001) of biliary fistula. Timing of drains removal did not influence complications. Drains amylase levels predict clinically relevant POPF. Drains should be maintained up to POD3; in case of POD1 DA levels < 666 U/L and POD3 DA levels < 252 U/L drains could be removed. In case of POD3 DA levels, ≥ 207 the routine use of abdominal CT scan in the same day could be justified to detect collections ≥ 5 cm and maintain drains beyond the POD3.

Synergistic Analysis of Protein Corona and Haemoglobin Levels Detects Pancreatic Cancer.

Simultaneous detection of multiple analytes from a single biological sample is gaining more attention in the development of more reliable and point-of-care diagnostic devices. We developed a multiplexed strategy that combined outcomes of clinical biomarkers with analysis of the protein corona that forms around graphene oxide sheets upon exposure to patient's plasma. As a paradigmatic case study, we selected pancreatic ductal adenocarcinoma (PDAC), mainly because of the absence of effective detection strategies that resulted in an extremely low five-year survival rate after diagnosis (<10%). Association of protein corona analysis and haemoglobin levels discriminated PDAC patients from healthy volunteers in up to 90% of cases. If further confirmed in larger-cohort studies, this approach may be used in the detection of PDAC.

Converting the personalized biomolecular corona of graphene oxide nanoflakes into a high-throughput diagnostic test for early cancer detection.

Advances in nanotechnology are introducing the exciting possibility of cancer identification at early stages via analysis of the personalized biomolecular corona (BC), i.e. the dynamic "halo" of proteins that adsorbs onto NPs following exposure to patients' plasma. In this study, we develop a blood test for early cancer detection based on the characterization of the BC that forms around Graphene Oxide (GO) nanoflakes. Among its elective properties, GO binds low amounts of albumin, the most abundant protein in the blood and one of the most enriched proteins in the BC of many nanomaterials. This unique property of GO allows strong adsorption of poorly concentrated plasma proteins without abundant protein depletion. In our study, GO nanometric flakes have been used to analyze BCs from 50 subjects, half of them diagnosed with pancreatic cancer and half of them being healthy volunteers. Pancreatic cancer was chosen as the model of a high mortality disease with poor survival rates due to its delayed diagnosis. The receiver operating characteristic (ROC) curve analysis was applied to measure the diagnostic accuracy of the BC-based test. We obtained an area under the curve (AUC) of 0.96 and the test discriminated cancer patients from healthy subjects with a sensitivity of 92%. Finally, a double-blind validation was made using a second test dataset (10 healthy subjects + 10 pancreatic cancer patients) and it confirmed the results obtained on the first training dataset. Being highly accurate, fast, inexpensive and easy to perform, we believe that the BC-enabled blood test has the potential to become a turning point in early detection of cancer and other diseases.