Impact on Long-term Survival of a Standardized Histopathological Protocol on the R1 Incidence in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is a pathology with a very poor prognostic, the only curative treatment option being surgery, in association with chemotherapy. This study aims to assess the influence that the use of a standardized pathology report after a pancreaticoduodenectomy (PD) has on the R1 margins rate and the impact that this has on long term survival. Material and Methods: We included 116 patients admitted to the Regional Institute of Gastroenterology and Hepatology Prof. Dr. O. Fodor Cluj Napoca, who underwent PD for PDAC (Pancreatic Ductal Adenocarcinoma) between January 2012 and May 2017. We divided them in two groups: 59 patients for which a nonstandardized histopathological protocol was used and 57 patients for which a standardized protocol was implemented. We considered a margin to be R1 when there were tumor cells at ¤ 1 mm from the resection margin. Results: The R1 percentage in the first group of patients was of 39%, while the R1 resection rate in the second group was of 68.4%. The median survival rate was similar in the two groups, with no statistically significant difference between them, but in the prospective study when comparing R0 vs R1 margins there was a statistically differences in 5 year OS with a p-value = 0.03. Conclusion: The use of a standardized pathology report reveals a significant increase in R1 resection rates. Also study revealed not only increasing R1 incidence when using a standardized histopathology report, but also that those margins (R1) playing a determinant role in 5-year OS. The mesopancreas is the most frequently R1 resection margin.

Robot-Guided Ultrasonography in Surgical Interventions.

INTRODUCTION: The introduction of robotic-guided procedures in surgical techniques has brought an increase in the accuracy and control of resections. Surgery has evolved as a technique since the development of laparoscopy, which has added to the visualisation of the peritoneal cavity from a different perspective. Multi-armed robot associated with real-time intraoperative imaging devices brings important manoeuvrability and dexterity improvements in certain surgical fields. MATERIALS AND METHODS: The present study is designed to synthesise the development of imaging techniques with a focus on ultrasonography in robotic surgery in the last ten years regarding abdominal surgical interventions. RESULTS: All studies involved abdominal surgery. Out of the seven studies, two were performed in clinical trials. The other five studies were performed on organs or simulators and attempted to develop a hybrid surgical technique using ultrasonography and robotic surgery. Most studies aim to surgically identify both blood vessels and nerve structures through this combined technique (surgery and imaging). CONCLUSIONS: Ultrasonography is often used in minimally invasive surgical techniques. This adds to the visualisation of blood vessels, the correct identification of tumour margins, and the location of surgical instruments in the tissue. The development of ultrasound technology from 2D to 3D and 4D has brought improvements in minimally invasive and robotic surgical techniques, and it should be further studied to bring surgery to a higher level.

Artificial Intelligence-Based Hazard Detection in Robotic-Assisted Single-Incision Oncologic Surgery.

THE PROBLEM: Single-incision surgery is a complex procedure in which any additional information automatically collected from the operating field can be of significance. While the use of robotic devices has greatly improved surgical outcomes, there are still many unresolved issues. One of the major surgical complications, with higher occurrence in cancer patients, is intraoperative hemorrhages, which if detected early, can be more efficiently controlled. AIM: This paper proposes a hazard detection system which incorporates the advantages of both Artificial Intelligence (AI) and Augmented Reality (AR) agents, capable of identifying, in real-time, intraoperative bleedings, which are subsequently displayed on a Hololens 2 device. METHODS: The authors explored the different techniques for real-time processing and determined, based on a critical analysis, that YOLOv5 is one of the most promising solutions. An innovative, real-time, bleeding detection system, developed using the YOLOv5 algorithm and the Hololens 2 device, was evaluated on different surgical procedures and tested in multiple configurations to obtain the optimal prediction time and accuracy. RESULTS: The detection system was able to identify the bleeding occurrence in multiple surgical procedures with a high rate of accuracy. Once detected, the area of interest was marked with a bounding box and displayed on the Hololens 2 device. During the tests, the system was able to differentiate between bleeding occurrence and intraoperative irrigation; thus, reducing the risk of false-negative and false-positive results. CONCLUSION: The current level of AI and AR technologies enables the development of real-time hazard detection systems as efficient assistance tools for surgeons, especially in high-risk interventions.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct.

INTRODUCTION: Ciliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct MATERIALS AND METHODS: 3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated RESULTS: Immunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma CONCLUSIONS: Our study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

Chitotriosidase and Neopterin as Two Novel Potential Biomarkers for Advanced Stage and Survival Prediction in Gastric Cancer-A Pilot Study.

Gastric cancer is the fifth type of neoplasia most frequently diagnosed and the fourth cause of death among other cancers. Prevalence is around two times higher for males than females. Chitotriosidase and neopterin are two molecular biomarkers with potential diagnostic and prognostic use in malignant pathology. We conducted a longitudinal prospective cohort study on thirty-nine patients with gastric adenocarcinoma, with a male-to-female ratio of 1.78 and an average age of 64.3 ± 9.97 years. No statistically significant differences in biomarker levels at presentation were observed between curative-intent surgery (28 patients) and advanced cases, suited only for palliative procedures (11 patients). Biomarker values were not significantly different for the advanced T stage and the presence of metastasis (p > 0.05-Mann Whitney test). The patients that died in the first 30 days after surgery did not present significantly different values at baseline, in comparison with those that had longer survival times, though a significant cut-off value was observed for chitotriosidase activity at 310 nmol/mL/h [AUC (area under the curve) = 0.78; 95% CI (0.61-0.92)]. The cut-off values corresponding to death after the first year, tumor invasion, and metastasis were not statistically significant. In the COX multivariate model, neopterin did not validate itself as a prognostic biomarker, however, chitotriosidase activity before surgery was significantly associated with overall survival (HR = 1.0038, p = 0.03). We conclude that chitotriosidase may have the potential to improve the prognostic model for gastric adenocarcinoma.

Editorial.

Pancreatic cancer is the fourth biggest cause of cancer-related fatalities in the World and generally affects people in their sixth to eighth decades. Cigarette smoking, obesity, high alcohol intake and chronic pancreatitis are underlying risk factors. The majority of pancreatic carcinomas are ductal adenocarcinomas, frequently developed on the head of the pancreas. Due to the delayed emergence of clinical symptoms, the pathology is often detected in a late stage (e.g. epigastric pain, painless jaundice and weight loss). When the primary tumor is diagnosed, it has often already advanced to other organs, primarily the liver. Surgical excision is only achievable in around 20 percent of patients, therefore palliative care is generally the sole option. The most prevalent surgical procedure performed is pancreaticoduodenectomy (Whipple procedure). Survival rates at five years vary from 3 to 40% depending on the size, spread and resectability of the tumor. Imaging may sometimes detect tiny, possibly resectable pancreatic lesions. These lesions may be benign, premalignant or malignant. Pancreatic cystic lesions and pancreatic neuroendocrine tumors profit from special medical and surgical treatment. Screening is not conducted frequently, although it is advised for selected, high-risk patients.

The Role of Radio-Frequency and Stereotactic Ablation in the Treatment of Pancreatic Cancer.

Pancreatic adenocarcinoma is a very aggressive tumor with a low overall survival rate. The prognostic and the treatment of this disease are strongly interconnected and highly dependent on the resectability criteria of the tumor, surgical excision being the golden standard. For local advance disease or for unresectable tumors, with or without metastasis we can take into consideration as adjuvant therapy, together with chemotherapy, the radiofrequency ablation or stereotactic ablation radiotherapy of the solid tumor mass. This article is a narrative review that aims to describe these two interventional techniques: radiofrequency ablation and stereotactic ablation radiotherapy. We will discuss the techniques themselves, benefits that they bring and also, about the possible complications that can appear when using them in the management of pancreatic cancer.

Perioperative Management of Patients with Pancreatic Cancer - the ERAS Protocols.

Background: Pancreatic cancer represents the fifth leading cause of death in industrialized countries. The prognosis is reserved, surgical resection being the only curative treatment, but the complications associated bear important impact on the patients survival, prognosis, and quality of life. The ERAS protocols come to meet these shortcomings for enhanced recovery after major pancreatic resections. Material and method: A systematic review was performed following the guidelines outlined by The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original articles published in the online databases Pubmed (Medline), Embase and Cochrane since 2017 until 2022 were screened after using specific keywords. Results: A total of 252 studies was obtained by searching through online databases. Following the exclusion criteria, we included 7 studies in the systematic review. Conclusions: The ERAS protocols are safe to be applied in the common practice. They are efficient in the perioperative management of patients undergoing pancreatic resections. They can further decrease hospitalization stay, promote better recovery of gastrointestinal function, and speed up postoperative recovery.

Pancreatic Adenocarcinoma Associated to Intraductal Papillary Mucinous Neoplasia: Histopathological Particularities and Clinical Implications.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor, known for an aggressive evolution. Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor, considered a premalignant lesion with the possibility of carcinogenesis towards PDAC. The clinical, surgical and histopathological particularities of the association between PDAC and IPMN are yet unknown, further research being needed. Methods: We have conducted a retrospective descriptive study, on a nine-year period (2012-2020), with the aim of comparing the characteristics of patients that underwent curative surgical interventions for solitary PDAC and PDAC associated to IPMN. Results: Fifteen patients with PDAC associated with IPMN (Group 1) and 386 patients with solitary PDAC (Group 2) were included in our study. Group 1 had a younger average age (61.8 years) compared to Group 2 (63.89 years). Total pancreatectomy was more frequently performed for Group 1 than Group 2 (33.33% vs 12.43%). Group 1 had a higher percentage of cases with positive perineural, perilymphatic and perivascular invasion. Group 1 registered a worse overall survival, as well as a worse short-time survival compared to Group 2. Conclusions: PDAC associated to IPMN registers distinct epidemiological, clinical and histopathological characteristics compared to solitary PDAC.

Duodenopancreatectomy for PDAC Associated with MALS: A Case Report.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic malignancy which occurs in over 90% of such cases. Pancreaticoduodenectomy (PD) is used with a curative purpose for localized PDAC. Case presentation: A 68-year-old woman presented to our service through a transfer from another service, to be investigated and treated for a head of the pancreas tumor in a tertiary referral hospital. After a complete clinical and paraclinical evaluation, the patient was diagnosed with a PDAC and also with a median arcuate ligament syndrome (MALS). The surgical treatment was considered adequate, therefore, the patient underwent a PD with transmesocolic hepaticojejunostomy, pancreaticogastric anastomosis, precolic end-to-side gastrojejunostomy, Witzel jejunostomy and with the help of the cardiovascular surgery team from the Heart Institute, Cluj- Napoca, an aortohepatic bypass using saphenous vein graft was performed. Conclusion: Bypass was essential because the blood flow in the proper hepatic artery was not restored after sectioning the median arcuate ligament and clamping the gastroduodenal artery. The patient had a favorable outcome. The particularity of the present case consists of the complete occlusion of the celiac trunk by MALS and the total vascularization of the supramesocolic organs due to the superior mesenteric artery through the gastroduodenal artery.

Risk Assessment-Oriented Design of a Needle Insertion Robotic System for Non-Resectable Liver Tumors.

Medical robotics is a highly challenging and rewarding field of research, especially in the development of minimally invasive solutions for the treatment of the worldwide leading cause of death, cancer. The aim of the paper is to provide a design methodology for the development of a safe and efficient medical robotic system for the minimally invasive, percutaneous, targeted treatment of hepatocellular carcinoma, which can be extended with minimal modification for other types of abdominal cancers. Using as input a set of general medical requirements to comply with currently applicable standards, and a set of identified hazards and failure modes, specific methods, such as the Analytical Hierarchy Prioritization, Risk Analysis and fuzzy logic Failure Modes and Effect Analysis have been used within a stepwise approach to help in the development of a medical device targeting the insertion of multiple needles in brachytherapy procedures. The developed medical device, which is visually guided using CT scanning, has been tested for validation in a medical environment using a human-size ballistic gel liver, with promising results. These prove that the robotic system can be used for the proposed medical task, while the modular approach increases the chances of acceptance.

Up to Date and Perspectives for Hepatocellular Carcinoma\'s Intraoperative Ultrasound.

With all the technological progress registered so far, hepatocellular carcinoma is still a diagnostic and therapeutic challenge, the optimal management being ensured only by a personalized attitude, offered by a multidisciplinary approach. Ultrasound plays an essential role in the guidelines for this neoplasm, the intraoperative application being mandatory to increase the survival of these patients, when the surgical approach is possible and indicated. This paper highlights the main indications for intraoperative ultrasound in the diagnosis and treatment of hepatocellular carcinoma, along with areas that have developmental potential.

Portojejunostomy: A Salvage Technique for Extrahepatic Bile Ducts Surgery.

As laparoscopic surgery has evolved, open cholecystectomy has been replaced with a new minimally invasive approach which is considered nowadays the gold-standard technique. Laparoscopic cholecystectomy has brought multiple advantages in terms of outcomes; however, the incidence of complex biliary injuries has been noticed. The portojejunostomy was first performed for pediatric patients with biliary atresia, involving the attachment of a Roux-en- Y loop to the porta hepatis in order to restore the bilioenteric continuity. In complex cases, with no options of reconstruction after biliary lesions, this technique has become a salvage procedure in adult surgery.

Is There a Role for Surgery in BCLC B Hepatocellular Carcinoma?

Intermediate stage hepatocarcinoma, classified b Barcelona Clinic Liver Cancer (BCLC) comprises a large number of patients, with diverse characteristics, being defined by multiple tumours, preserved liver function and good performance status. The recommended treatment for this stage is transarterial chemoembolization (TACE), but there are a few studies that discuss the role of surgery in this stage. We report a case of a 59-year-old woman diagnosed with BCLC B hepatocarcinoma (two tumours of 34 and 25 mm, in liver segments 5 and 6) who was successfully treated with surgical resection. This patient had additional risk factors like morbid obesity, clinically significant portal hypertension, and thrombocytopenia. Despite these characteristics, the evolution was favourable. In conclusion, we believe that surgery has an important role in the treatment of well-selected BCLC B patients and a good preoperative assessment of the patient can minimize the perioperative risk.

Synchronous Pancreatic Tumours: Intraductal Papillary Mucinous Neoplasm with Pancreatic Ductal Adenocarcinoma and Neuroendocrine Tumour: A Case Presentation and Review of Literature.

Synchronous tumours of the pancreas are rare encounters, with few reported cases. Thus, new information can be brought about the diagnosis, proper management, and prognosis of cases. We believe that the presentation of this case can help to establish relevant conclusions. We report the case of a 54-year-old man, with the preoperative diagnosis of a cephalic intraductal papillary mucinous neoplasm (IPMN), who underwent a planned cephalic pancreatoduodenectomy with completion to total pancreatectomy based on the intraoperative extemporaneous histopathological examination of the resection margin. The final histopathological diagnosis was cephalic IPMN associated with invasive ductal adenocarcinoma (PDAC) and a small well-differentiated neuroendocrine tumour (NET) in the tail of the pancreas. No recurrence was detected in the 3 years of follow-up. We conducted a review of the literature to illustrate the particularities of the presented case; it identified 4 articles about the association of PDAC and NET and 8 articles regarding the association of IPMN with NET. Only 2 patients had a histopathological diagnosis of three synchronous tumours (IPMN, PDAC, and NET). We present a rare case of three synchronous pancreatic tumours, with a favourable evolution after a total pancreatectomy, only two other similar cases being reported in medical literature.

The Role of miR-155 in Nutrition: Modulating Cancer-Associated Inflammation.

Nutrition plays an important role in overall human health. Although there is no direct evidence supporting the direct involvement of nutrition in curing disease, for some diseases, good nutrition contributes to disease prevention and our overall well-being, including energy level, optimum internal function, and strength of the immune system. Lately, other major, but more silent players are reported to participate in the body's response to ingested nutrients, as they are involved in different physiological and pathological processes. Furthermore, the genetic profile of an individual is highly critical in regulating these processes and their interactions. In particular, miR-155, a non-coding microRNA, is reported to be highly correlated with such nutritional processes. In fact, miR-155 is involved in the orchestration of various biological processes such as cellular signaling, immune regulation, metabolism, nutritional responses, inflammation, and carcinogenesis. Thus, this review aims to highlight those critical aspects of the influence of dietary components on gene expression, primarily on miR-155 and its role in modulating cancer-associated processes.

Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI+MS.

Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI+ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the "lipogenic phenotype" specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.

Serum levels of soluble programmed death-ligand 1 (sPD-L1): A possible biomarker in predicting post-treatment outcomes in patients with early hepatocellular carcinoma.

BACKGROUND: There have been great advances in hepatocellular carcinoma management over the last years. However, there are still no prognostic biomarkers that can identify patients who will benefit the most from curative treatments. We aimed to investigate whether sPD-L1 levels measured before curative treatment is a prognostic biomarker of survival in patients with HCC. METHODS: HCC patients from a prospectively collected database were selected and soluble programmed death-ligand1(sPD-L1) levels were determined. The association of sPD-L1 levels and overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS: One hundred twenty-one patients with HCC were included. The best cut-off value of sPD-L1 for both DFS and OS was 96 pg/mL. Patients with a high sPD-L1 value (>96 pg/mL) had a shorter disease free survival and OS (hazard ratio 5.42, 95% confidence interval 2.28-12.91, p < 0.001, and hazard ratio 9.67, 95% confidence interval 4.33-21.59, p < 0.001). High sPD-L1 levels were associated with mortality independently from other known survival predictors. We found a positive correlation between sPD-L1 and PD-L1 expression in cancer cells (p = 0.01). In 16 out of 38 patients, sPD-L1 levels decreased from baseline value on week 6 after treatment and in 22 out of 38 patients, sPD-L1 levels increased from the baseline value. However, fluctuations of sPD-L1 in time had no influence on survival (p = 0.148). CONCLUSION: We conclude that a high sPD-L1 level is a biomarkerfor a poor outcome in HCC. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future.

Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver.

To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones' volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm3, 19.22 ± 5.77 cm3, and 8.80 ± 3.33 cm3 for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.

Integration of Real-Time Image Fusion in the Robotic-Assisted Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, with its mortality rate correlated with the tumor staging; i.e., early detection and treatment are important factors for the survival rate of patients. This paper presents the development of a novel visualization and detection system for HCC, which is a composing module of a robotic system for the targeted treatment of HCC. The system has two modules, one for the tumor visualization that uses image fusion (IF) between computerized tomography (CT) obtained preoperatively and real-time ultrasound (US), and the second module for HCC automatic detection from CT images. Convolutional neural networks (CNN) are used for the tumor segmentation which were trained using 152 contrast-enhanced CT images. Probabilistic maps are shown as well as 3D representation of HCC within the liver tissue. The development of the visualization and detection system represents a milestone in testing the feasibility of a novel robotic system in the targeted treatment of HCC. Further optimizations are planned for the tumor visualization and detection system with the aim of introducing more relevant functions and increase its accuracy.