Neoadjuvant Treatments for Pancreatic Ductal Adenocarcinoma: Where We Are and Where We Are Going

Background: Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC. Methods: A PubMed database search of articles published up to September 2022 was carried out. Results: Many studies showed that FOLFIRINOX or Gemcitabine-nab- paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro- metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process. Conclusions: The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery

Genome-Wide Association Analysis in Asthma Subjects Identifies SPATS2L as a Novel Bronchodilator Response Gene

Bronchodilator response (BDR) is an important asthma phenotype that measures reversibility of airway obstruction by comparing lung function (i.e. FEV1) before and after the administration of a short-acting β2-agonist, the most common rescue medications used for the treatment of asthma. BDR also serves as a test of β2-agonist efficacy. BDR is a complex trait that is partly under genetic control. A genome-wide association study (GWAS) of BDR, quantified as percent change in baseline FEV1 after administration of a β2-agonist, was performed with 1,644 non-Hispanic white asthmatic subjects from six drug clinical trials: CAMP, LOCCS, LODO, a medication trial conducted by Sepracor, CARE, and ACRN. Data for 469,884 single-nucleotide polymorphisms (SNPs) were used to measure the association of SNPs with BDR using a linear regression model, while adjusting for age, sex, and height. Replication of primary P-values was attempted in 501 white subjects from SARP and 550 white subjects from DAG. Experimental evidence supporting the top gene was obtained via siRNA knockdown and Western blotting analyses. The lowest overall combined P-value was 9.7E-07 for SNP rs295137, near the SPATS2L gene. Among subjects in the primary analysis, those with rs295137 TT genotype had a median BDR of 16.0 (IQR = [6.2, 32.4]), while those with CC or TC genotypes had a median BDR of 10.9 (IQR = [5.0, 22.2]). SPATS2L mRNA knockdown resulted in increased β2-adrenergic receptor levels. Our results suggest that SPATS2L may be an important regulator of β2-adrenergic receptor down-regulation and that there is promise in gaining a better understanding of the biological mechanisms of differential response to β2-agonists through GWAS

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Preoperative Misdiagnosis in Patients Undergoing Pancreatoduodenectomy

Distal bile duct cholangiocarcinoma, ampullary adenocarcinoma, duodenal carcinoma, and ductal adenocarcinoma (PDAC) of the head of the pancreas usually have similar clinical presentation since they arise in the same circumscribed anatomical area, within 2 cm of the major duodenal papilla [...

Preoperative Misdiagnosis in Patients Undergoing Pancreatoduodenectomy

Distal bile duct cholangiocarcinoma, ampullary adenocarcinoma, duodenal carcinoma, and ductal adenocarcinoma (PDAC) of the head of the pancreas usually have similar clinical presentation since they arise in the same circumscribed anatomical area, within 2 cm of the major duodenal papilla [...

Minimally invasive transthoracic resection of a segment eight liver tumor

Despite advances in technology and technique of minimally invasive liver surgery, resection of lesions in the posterosuperior segments such as segment 8 (S8) remains challenging. Compared to open surgery, there are specific differences that make minimally invasive access to S8 challenging. These include the caudal view along the axis of the hepatoduodenal ligament, increased distance between trocars and the operative field, and the liver fulcrum created by the anterolateral segments limiting the view. However, several advancements have helped to overcome these challenges, such as the use of intercostal trocars (combined lateral-abdominal approach) and a flexible tip camera. Consequently, a total thoracoscopic (transthoracic) approach was developed to resect subdiaphragmatic tumors, which may particularly benefit patients with a hostile abdomen. This article summarizes the anatomic, technical, and technological considerations for safe resection of lesions in S8

Artificial intelligence and its role in guiding liver-directed therapy for hepatocellular carcinoma: Is it ready for prime time?

Artificial intelligence (AI) is an innovative discipline in medicine, impacting both hepatology and hepato-pancreato-biliary surgery, ensuring reliable outcomes because of its repeatable and efficient algorithms. A considerable number of studies about the efficiency of AI in the management of hepatocellular carcinoma (HCC) have been published. While its diagnostic role is well recognized, providing large amounts of quantitative radiological HCC features, its use in HCC treatment is still debated. Innovative use of AI may help to select the best approach for each patient as it is able to predict the outcomes after resection and/or other treatments. In this review, we assess the role of AI in selecting the best therapeutic option and predicting long-term risks after surgical or interventional treatments for HCC patients. Further studies are needed to consolidate AI applications

The impact of intraoperative ultrasonography on the management of disappearing colorectal liver metastases

Hepatic resection for colorectal liver metastases (CRLM) is currently the only treatment option that can offer a chance of long-term survival, with 5-year survival rates of 40% [1\u20133], and exceeding 50% in selected patients [4\u20136]. However, resectability is the limiting factor; indeed, only 10\u201325% of patients with CRLM are candidates for surgical resection at the time of presentation [7]. More recently, the introduction of new and more effective chemotherapy regimens combined with targeted agents have improved the response rate over that of standard chemotherapy alone, from 30 to 60% [8\u201310]. For this reason preoperative chemotherapy for CRLM has been widely used and an increasing number of patients receive chemotherapy prior to liver resection, either as neoadjuvant strategy for initially resectable CRLM [11], or as conversion chemotherapy in patients with initially unresectable CRLM in attempt to convert them into surgical candidates [12,13]. The extensive use of chemotherapy may cause the shrinkage of CRLM and sometimes makes such lesions impossible to identify in radiological imaging studies. These lesions are called \u2018missing\u2019 or \u2018disappearing\u2019 CRLM [14]. Disappearing liver metastases (DLM) are defined as a disappearance of liver metastases on cross-sectional imaging after administration of preoperative chemotherapy, which means a complete radiological response or complete clinical response (CCR). This phenomenon has been reported by several centers and can occur in 5\u201325% of patients who undergo preoperative systemic chemotherapy [15\u201321]. Patients with multiple CRLM, with size <1 cm and those undergoing prolonged preoperative chemotherapy, presented significantly higher risk of developing DLM [18]. Different reported rates of DLM may depend on the quality and type of cross-sectional imaging [22]. Indeed preoperative chemotherapy can induce parenchymal changes to the liver by increasing fatty content, defined as steatosis or steatohepatitis. In that setting the background liver appears less dense, with lower contrast between the parenchyma and the hypovascular metastases, hindering their detection [14,22]. Compared with computed tomography (CT), magnetic resonance imaging (MRI) with liver-specific contrast agents, presents higher sensitivity and better specificity to detect and differentiate CRLM, and can be considered as the best modality to image CRLM missing on CT scan, especially in case of chemotherapy-induced steatosis or steatohepatitis [14,22,23]