Team Strategy Optimization in Combined Resections for Synchronous Colorectal Liver Metastases. A Comparative Study with Bootstrapping Analysis.

BACKGROUND: The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. METHODS: Within four referral centers, a group of 234 patients treated in 1-T centers was identified and compared with a group of 253 patients treated in 2-T. A nonparametric bootstrap process was applied to the original cohorts of 1-T group and 2-T group as a resampling method to obtain bootstrapped cohorts (155 patients per group). RESULTS: 33.5% of patients in 1-T boot group and 38.1% in the 2-T boot group were operated by laparoscopic approach. Multivariate analysis revealed that approach to primary tumor (laparoscopic or open) and intraoperative blood loss were independent prognostic factors for morbidity. Team approach did not show any significant correlation with incidence of postoperative complications nor with choice for laparoscopic approach. CONCLUSION: The optimization of team strategy for patients with SCRLM is not solely based on the adoption of a 1-T or 2-T approach, but should instead be based on the implementation of a standard protocol for management of these patients.

Periostin, tenascin, osteopontin isoforms in long- and non-long survival patients with pancreatic cancer: a pilot study.

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR. LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.

Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: a pilot study.

BACKGROUND: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. METHODS: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. RESULTS: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. CONCLUSION: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

The impact of extent of pancreatic and venous resection on survival for patients with pancreatic cancer.

BACKGROUND: Borderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC). METHODS: This was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival. RESULTS: Ninety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31-3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27-3.15; P = 0.003) as the only independent prognostic factors for overall survival. CONCLUSIONS: Up-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Importance of primary indication and liver function between stages: results of a multicenter Italian audit of ALPPS 2012-2014.

BACKGROUND: Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates. METHOD: A national audit was performed to gather information about the safety of the procedure and to better understand the complications. The audit was offered to all high-volume hepatobiliary centers in Italy. RESULTS: Of all Italian centers approached in January 2012, 12 centers with experience in ALPPS enrolled and participated in collection of data. Fifty patients underwent ALPPS between 2012 and 2014. In 48/50 patients completion of hepatectomy was performed successfully. Major morbidity occurred in 54% with a 20% 90-day mortality. Uni- and multivariate analysis showed that ALPPS for cholangiocarcinoma and a peak of bilirubin over 5 mg/dl between stages was associated with increase of 90-day mortality and worse survival. DISCUSSION: It is proposed that a moratorium be introduced for classic ALPPS in cholangiocarcinoma and to abort ALPPS in patients who develop an interstage increase in bilirubin, due to the high risk of liver failure and mortality.

Strategies to Increase the Resectability of Patients with Colorectal Liver Metastases: A Multi-center Case-Match Analysis of ALPPS and Conventional Two-Stage Hepatectomy.

BACKGROUND: Two-stage hepatectomy (TSH) is well established for the treatment of patients who have colorectal cancer liver metastases (CRLM) with a small liver remnant. The technique of associating liver partitioning and portal vein occlusion for staged hepatectomy (ALPPS) has been advocated as a novel tool to increase resectability. Using a case-match design, this study aimed to compare TSH and ALPPS for patients with CRLM. METHODS: All patients undergoing ALPPS for CRLM at three major hepatobiliary centers in Italy (ALPPS group) were compared in a case-match analysis with patients undergoing TSH (TSH group) at a single institution. The groups were matched with a 1:3 ratio using propensity scores based on covariates representing severity of metastatic disease. The main end points of the study were feasibility of complete resection and intra- and postoperative outcomes. RESULTS: The two treatments did not differ significantly in feasibility. Two patients in the TSH group dropped out compared with no patients in the ALPPS group. A comparable volume gain in future liver remnant (FLR) was obtained in the ALPPS and TSH groups (47 vs. 41 %, nonsignificant difference) but during a shorter interval in ALPPS group. The overall and major complication rate was significantly higher after stage 2 in the ALPPS group (Clavien ≥ 3a: 41.7 vs. 17.6 % in TSH group; p = 0.025). CONCLUSION: The feasibility of resection using ALPPS compared with TSH for CRLM was not significantly greater, but perioperative complications were increased. Therefore, ALPPS should be proposed to patients with caution and warnings. Currently, TSH remains the standard approach for performing R0 resection in patients with advanced CRLM and inadequate FLR.

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers.

Urgent ERCP performed with single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis: Single-center prospective study.

Background and study aims To assess the outcomes of urgent endoscopic retrograde cholangiopancreatography (ERCP) performed with a single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis. Patients and methods Between 2021 and 2022 consecutive patients with moderate-to-severe cholangitis were prospectively enrolled to undergo urgent ERCP with SUD. Technical success was defined as the completion of the planned procedure with SUD. Multivariate analysis was used to identify factors related to incidence of adverse events (AEs) and mortality. Results Thirty-five consecutive patients (15 female, age 81.4±6.7 years) were enrolled. Twelve (34.3%) had severe cholangitis; 26 (74.3%) had an American Society of Anesthesiologists (ASA) score ≥3. Twenty-eight patients (80.0%) had a naïve papilla. Biliary sphincterotomy and complete stone clearance were performed in 29 (82.9%) and 30 patients (85.7%), respectively; in three cases (8.6%), concomitant endoscopic ultrasound-gallbladder drainage was performed. Technical and clinical success rates were 100%. Thirty-day and 3-month mortality were 2.9% and 14.3%, respectively. One patient had mild post-ERCP pancreatitis and two had delayed bleeding. No patient or procedural variables were related to AEs. ASA score 4 and leucopenia were related to 3-month mortality; on multivariate analysis, leukopenia was the only variable independently related to 3-month mortality (odds ratio 12.8; 95% confidence interval 1.03-157.2; P =0.03). Conclusions The results of this "proof of concept" study suggest that SUD use could be considered safe and effective for urgent ERCP for acute cholangitis. This approach abolishes duodenoscope contamination from infected patients without impairing clinical outcomes.

Intraperitoneal mesh open repair without dissection technique for large ventral hernia repair: an alternative to component separation technique.

BACKGROUND: Incisional hernias (IH) are one of the major complications following abdominal surgery and the treatment of large abdominal hernias represents a challenge for the surgeon. We present our own modified open intraperitoneal mesh technique, named "IPOW technique" (intra-peritoneal mesh open repair without dissections). METHODS: We analyzed early postoperative complications (seroma, wound infection, hematoma) and the late ones (recurrence, chronic pain), in 50 unselected patients treated for IH and primary hernia (PH) larger than 5 cm using the proposed laparotomic technique. RESULTS: From January 2019 to September 2021, 50 unselected patients with, at least, one year of follow-up, with hernias ranging from 5 to 25 cm in width, were surgically repaired using IPOW technique. Mean Body Mass Index (BMI) was 29 (range 22-44). In our series, we report 2 (4%) complications and, after a mean follow-up of 847 days (range 481-1357), 2 (4%) recurrences. No patients reported chronic pain. CONCLUSIONS: In our experience, we consider IPOW technique easily reproducible, ensuring excellent results with a reduction of invasiveness, comparing to other techniques. Anyway, definitive conclusions require a larger number of patients.

The role of laparoscopic IPOM in the treatment of abdominal hernias: lesson learned after 400 surgeries using single mesh.

BACKGROUND: Abdominal wall hernias and incisional hernias are a common benign disorder affecting quality of life, potentially leading to life-threatening complications. Laparoscopic IPOM (intraperitoneal onlay mesh) approach can offer good results in selected cases. METHODS: Patients who underwent laparoscopic incisional/ventral abdominal hernia repair operated with standardized technique and the same mesh, from January 2011 to December 2022, were retrospectively considered. RESULTS: Four hundred consecutive patients underwent laparoscopic abdominal wall repair. There were 255 ventral hernia (63%) and 145 (37%) primitive hernia (epigastric and umbilical). Mean size of the defect was 4.2 cm, W3 were 19 (4%). After a mean follow-up of 1906 days (range 45-4109), no mesh-related complications have been detected. There were 10 (2.5%) recurrences and 20 (5%) bulging. CONCLUSIONS: In this study we emphasized the role of patient selection and standardized technique which represents "the lesson" learned over a period of 15 years of activity. In this setting, we believe that laparoscopic approach can achieve very good results in abdominal wall repair.

Robotic Hartmann's reversal-feasibility and technical aspects.

Hartmann's reversal as a staged procedure after emergency surgery is a major abdominal operation with undeniable skill-demanding steps. The robotic approach and its advantages seem to be a safe and feasible technique and could overcome necessary technical compromises of laparoscopy, ensuring a significant reduction in restoration failures or conversion.

Simultaneous resection of colorectal cancer and synchronous liver metastases: what determines the risk of unfavorable outcomes? An international multicenter retrospective cohort study.

BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes. METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression. RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013). CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections.

Very high CEA level in a large pancreatic cyst: is it a surgical indication by itself?

BACKGROUND: Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. METHODS: A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). RESULTS: The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. CONCLUSIONS: Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value? Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

Minimally invasive treatment of colorectal liver metastases: does robotic surgery provide any technical advantages over laparoscopy? A multicenter analysis from the IGoMILS (Italian Group of Minimally Invasive Liver Surgery) registry.

Surgery has been the mainstay treatment for colorectal liver metastases (CRLM). Although the benefits of a laparoscopic approach have been evidenced by several comparative studies, the comparison between robotic and laparoscopic liver surgery has not been elucidated. Thus, in this study, we aim to analyze the short-term outcomes of a multicenter population that underwent robotic versus laparoscopic liver resection for CRLM. Consecutive patients with CRLM who were enrolled in the IGoMILS registry between November 2014 and June 2019 were retrospectively evaluated to compare robot-assisted procedures with laparoscopic procedures. Primary outcomes were postoperative morbidity and mortality, while secondary outcomes were length of hospital stay, operative time, and histological features of the surgical specimen. The effect size of surgical technique on resection margins was quantified using Hedges' g. In total, 1030 patients underwent minimally invasive liver surgery (MILS) for CRLM; of these, 77 (7.5%) underwent a robot-assisted approach (R-MILS), whereas 953 (92.5%) underwent a laparoscopic approach (L-MILS). Laparoscopy and robot-assisted surgery were comparable in terms of postoperative outcomes: specifically, complication rates, Comprehensive Complication Index (CCI®), intraoperative blood loss, conversion rate, operative time, and length of hospital stay did not differ significantly between the two groups. R-MILS showed a reduced rate of R1 resection margins (19.9 vs. 28.8%, p = 0.025) and wider surgical margins compared with L-MILS (8 vs. 3 mm, p < 0.001). The effect size of robot-assisted surgery was increased for posterosuperior lesions (g = 0.78) and difficult procedures (g = 1.92). As per our findings, it was determined that robot-assisted liver surgery offers some technical advantages over conventional laparoscopy, maintaining the benefits of minimally invasive surgery on short-term outcomes.

Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel.

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients.

HHV-6A in syncytial giant-cell hepatitis.

Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.

Molecular alterations in pancreatic tumors.

Genetic alterations in pancreatic tumors can usually be classified in: (1) Mutational activation of oncogenes; (2) Inactivation of tumor suppressor genes; and (3) Inactivation of genome maintenance genes controlling the repair of DNA damage. Endoscopic ultrasound-guided fine-needle aspiration has improved pre-operative diagnosis, but the management of patients with a pancreatic lesion is still challenging. Molecular testing could help mainly in solving these "inconclusive" specimens. The introduction of multi-gene analysis approaches, such as next-generation sequencing, has provided a lot of useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic tumors (e.g., pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, solid pseudopapillary tumors) are characterized by specific molecular alterations. The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

Urgent and emergency surgery for secondary peritonitis during the COVID-19 outbreak: an unseen burden of a healthcare crisis.

The COVID-19 pandemic has raised concerns about the negative impact of the fear of contagion on people's willingness to seek medical care and the subsequent effects on patients' prognosis. To date, not much is known about the outcomes of acute surgical diseases in this scenario. The aim of this multicenter observational study is to explore the effects of COVID-19 outbreak on the outcomes of patients who underwent surgery for peritonitis. Patients undergoing surgery for secondary peritonitis during the first COVID-19 surge in Italy (March 23-May 4, 2020-COVID period group) were compared with patients who underwent surgery during the same time interval of year 2019 (no-COVID period group). The primary endpoint was the development of postoperative complications. Logistic regression analysis was conducted to identify predictors of complications. Of the 332 patients studied, 149 were in the COVID period group and 183 were in the no-COVID period group. Patients in the COVID period group had an increased frequency of late presentations to the emergency departments (43% vs. 31.1%; P = 0.026) and a higher rate of postoperative complications (35.6% vs. 18%; P < 0.001). The same results were found in the subset analysis of patients with severe peritonitis at surgical exploration. The ASA score, severity of peritonitis, qSOFA score, diagnosis other than appendicitis, and COVID period resulted independent predictors of complications. During the COVID-19 pandemic patients with peritonitis had a higher rate of complicated postoperative courses, weighing on hospital costs and assistance efforts already pressured by the ongoing sanitary crisis.