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.

Efficiency of Simulation-Based Learning Using an ABC POCUS Protocol on a High-Fidelity Simulator.

Critically ill patients with rapidly deteriorating clinical status secondary to respiratory and cardio-vascular compromise are at risk for immediate collapse if the underlying pathology is not recognized and treated. Rapid diagnosis is of utmost importance regardless of the setting. Although there are data to support the use of point-of-care ultrasound in critical patients, there is no consensus about the best educational strategy to implement. We designed a curriculum based on the ABC (Airway, Breathing, Circulation) protocol that covers essential airway, lung, and cardiac ultrasound skills needed for fast diagnosis in critical patients and applied it in high-fidelity simulation-based medical education sessions for anesthesia and intensive care residents year one and two. After theoretical and practical assessments, our results show statistical differences in the theoretical knowledge and above-average results in practical assessment. Our proposed curriculum based on a simple ABC POCUS protocol, with an Airway, Breathing, and Circulation approach, is useful in teaching ultrasound basics regarding airway, lung, and cardiac examination using high-fidelity simulation training to anesthesia and intensive care residents, but further research is needed to establish the utility of Simulation-Based Medical Education in Point of Care Ultrasound in the critical patient.

Laparoscopic Pancreatoduodenectomy in Elderly Patients: A Systematic Review and Meta-Analysis.

Background and Aims: Recent single-center retrospective studies have focused on laparoscopic pancreatoduodenectomy (LPD) in elderly patients, and compared the outcomes between the laparoscopic and open approaches. Our study aimed to determine the outcomes of LPD in the elderly patients, by performing a systematic review and a meta-analysis of relevant studies. Methods: A comprehensive literature review was conducted utilizing the Embase, Medline, PubMed, Scopus and Cochrane databases to identify all studies that compared laparoscopic vs. open approach for pancreatoduodenectomy (PD). Results: Five retrospective studies were included in the final analysis. Overall, 90-day mortality rates were significantly decreased after LPD in elderly patients compared with open approaches (RR = 0.56; 95%CI: 0.32−0.96; p = 0.037, I2 = 0%). The laparoscopic approach had similar mortality rate at 30-day, readmission rate in hospital, Clavien−Dindo complications, pancreatic fistula grade B/C, complete resection rate, reoperation for complications and blood loss as the open approach. Additionally, comparing with younger patients (<70 years old), no significant differences were seen in elderly cohort patients regarding mortality rate at 90 days, readmission rate to hospital, and complication rate. Conclusions: Based on our meta-analysis, we identify that LPD in elderly is a safe procedure, with significantly lower 90-day mortality rates when compared with the open approach. Our results should be considered with caution, considering the retrospective analyses of the included studies; larger prospective studies are required.

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.

Nanotechnology in the Diagnostic and Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma is the most common liver malignancy and is among the top five most common cancers. Despite the progress of surgery and chemotherapy, the results are often disappointing, in part due to chemoresistance. This type of tumor has special characteristics that allow the improvement of diagnostic and treatment techniques used in clinical practice, by combining nanotechnology. This article presents a brief review of the literature focused on nano-conditioned diagnostic methods, targeted therapy, and therapeutic implications for the pathology of hepatocellular carcinoma. Within each subdomain, several modern technologies with significant impact were highlighted: serological, imaging, or histopathological diagnosis; intraoperative detection; carrier-type nano-conditioned therapy, thermal ablation, and gene therapy. The prospects offered by nanomedicine will strengthen the hope of more efficient diagnoses and therapies in the future.

Analysis of the MLH1, MLH2, MLH6, PMS2 genes and their correlations with clinical data in rectal mucinous adenocarcinoma.

BACKGROUND: Microsatellites are short repeated DNA sequences normally found in the human genome. Following specific mutations, microsatellites can vary in the number of repeats thus making the DNA unstable. Microsatellite instability (MSI) is responsible for approximately 20% of rectal cancers, while the remaining 80% are caused by chromosomal instability. One of the following genes, MLH1, MLH2, MLH 6, and PMS2, is inactivated, leading to MSI colorectal cancers. AIM: This study aimed to analyze the expression of some MMR system genes presenting mutations in mucinous rectal cancer and their correlations with clinical data. METHODS: A retrospective study was performed on patients with rectal mucinous adenocarcinoma who underwent surgery between January 2000 and January 2017. We collected a total of 42 patients and analyzed the demographic data, histopathological results and MMR system genes mentioned above. RESULTS: Almost 93% of the cases analyzed had MSI-H and only 7% were MSI-L. For MLH1, 50% of stage T2 and 50% of stage T4 had weak expression, while in stage T3, 42.50% had moderate expression. Regarding the N stage, we found that 66.67% of the patients with moderate gene expression (2+) were N2, while 42% of the patients with weak expression were N0. For MSH2, the majority of patients with strong gene expression were in stage T3 (27%). Weak expression was found in 50% of the patients in stage T2, 35% of the patients in stage T3, and 33.3% in T4. In 44.44% of the weak expression was N2, while for strong expression, there was an equivalent percentage of 33.33% in stages N1 and N2. Describing the MSH6 gene, we found that the most heterogeneous results were in stage T3. Weak expression was observed in 38.46% of the patients, while moderate and strong expression was observed in 30.77% and 11.54% respectively. Analysis of PMS2 revealed that 66.67% of the patients in stage T4 had a weak expression of the gene, while the same expression was found in 38.46% of the patients in stage T3. A total of 23.08% of patients in stage T3 had strong gene expression. We also analyzed the overall gene expression. Thus, we found that three patients (7.14%) had only 1, three genes were expressed, nine (21.42%) had two genes and the remaining 27 patients had all 4. The 1-year survival rate in the analyzed lot was 75%, decreasing to 60% in the second year and 35% in the 3rd. There were no statistically significant differences in survival data between the stages or gene expression. CONCLUSIONS: Our study showed no statistical difference regarding the survival on different gene expression or staging, consistent with studies that found that mucin expression does not have a significant impact on local recurrence, nor does it affect nodal down staging. KEY WORDS: Mucinous adenocarcinoma, Microsatelites instability.

The Dynamics of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict Progression to Septic Shock and Death in Patients with Prolonged Intensive Care Unit Stay.

Background and objectives: The prognoses of patients experiencing a prolonged stay in the intensive care unit (ICU) are often significantly altered by hospital-acquired infections (HAIs), the early detection of which might be cumbersome. The aim of this study was to investigate the roles of the neutrophil-to-lymphocyte (NLR), derived-NRL (d-NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-C-reactive protein (LCR) ratios in predicting the progression to septic shock and death. Materials and Methods: A retrospective analysis of a consecutive series of ninety COVID-19 patients with prolonged hospitalization (exceeding 15 days) admitted to the ICU was conducted. The prevalence of culture-proven HAIs throughout their hospital stays was documented. NLR, dNLR, PLR, and LCR were recorded on admission, day 7, and day 14 to assess their discriminative prowess for detecting further progression to septic shock or death. Results: The prevalence of HAIs was 76.6%, 50% of patients met the criteria for septic shock, and 50% died. The median time to the first positive culture was 13.5 days and 20.5 days for developing septic shock. Mechanical ventilation was a key contributing factor to HAI, septic shock, and mortality. On admission and day 7 NLR, dNLR, PLR, and LCR values had no prognostic relevance for events occurring late during hospitalization. However, day-14 NLR, dNLR, and PLR were independent predictors for progression to septic shock and mortality and have shown good discriminative capabilities. The AUCs for septic shock were 0.762, 0.764, and 0.716, while the values for predicting in-hospital death were 0.782, 0.778, and 0.758, respectively. Conclusions: NLR, dNLR, and PLR are quick, easy-to-use, cheap, effective biomarkers for the detection of a more severe disease course, of the late development of HAIs, and of the risk of death in critically ill patients requiring a prolonged ICU stay.

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.

Short-term outcome and survival after multiorgan resection for locally advanced colo-rectal cancer. Identification of risk factors.

INTRODUCTION: Although multi-organ resections (MOR) are recommended by international guidelines for advanced colorectal cancer, the literature shows that the morbidity and mortality that accompanies these complex interventions limits the number of patients receiving this treatment. The purpose of our study was to analyse the immediate and remote results obtained after MOR and to identify potential factors that might influence the outcome. MATERIAL AND METHOD: Our study is a retrospective cohort which included patients surgically treated in our service for locally advanced colorectal cancer. We excluded patients with hepatic metastatic tumors and those who needed pelvic exenteration. Between 2006 and 2010, in our service, have been treated with MOR 146 patients, 107 being included in our study. We analysed morbidity, mortality and survival after MOR and the factors that could have influenced the postoperative course. RESULTS: Identified risk factors that negatively influenced the postoperative outcome were: diabetes, personal neoplastic pathologies, associated cardiovascular disease, history of major surgeries, intraoperative blood loss, number of resected organs. Survival was negatively influenced by positive resection margins, the presence of lymph node metastases and the presence of complications in the postoperative period. CONCLUSIONS: The data of this study support the indication for routine MOR for patients diagnosed with locally advanced colorectal cancer with the condition that R0 resection margins are achieved. All mentioned above underline the importance of the experience that the surgical team has in this type of surgeries, in order to achieve optimum results. This experience must concern the preoperative management, surgical technique and postoperative care. KEY WORDS: Colo-rectal cancer, Multi-organ resections, Risk factors.

Predictors of 1-year postoperative mortality in radical colon cancer surgery.

AIM: The aim of this study was to determine the impact of patient, tumor and surgery-related parameters on 1-year postoperative mortality in a cohort of patients operated in a single tertiary center. MATERIALS AND METHODS: The study included 605 patients diagnosed with colon cancer between January 2013 and December 2015 that underwent radical surgery in a tertiary center. Patient demographics, comorbidities, preoperative biological parameters alongside with tumor and surgery-related factors were prospectively recorded and then analyzed in relation 1-year postoperative mortality. RESULTS: One-year mortality rate in the study group was 10.9%. Independent risk factors in relation to 1-year mortality were advanced TNM stage (OR 3.10, 1.10 - 8.75 95% CI ), emergency surgery (OR 1.91, 1.11 - 3.74 95% CI ), location of the tumor in the ascending colon (OR 2.17, 1.32 - 3.57 95% CI ), multiorgan resections (OR 2.07, 1.15 - 3.74 95% CI), age over 63 years (OR 2.05, 1.16 - 3.62 95% CI) and the history of alcohol consumption (OR 2.058, 1.17 - 3.61 95% CI ). DISCUSSION: Postoperative complications are still being reported in colon cancer surgery, despite technological progress and constant research in the field. So far, factors that influence postoperative mortality have been mostly studied up to 30 days postoperatively. According to some recent papers, reporting 30-day mortality data can underestimate accurate communication of postoperative adverse events. Thus, 1-year mortality in colon cancer surgery could be a better indicator of the impact on surgery on postoperative period of this patients and factors that influence it should be well known. KEY WORDS: Surveillance, Colon cancer, 1-year mortality.

Quantum dots in imaging, drug delivery and sensor applications.

Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.

Carbon nanotubes as anti-bacterial agents.

Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

Development of nanoparticle-based optical sensors for pathogenic bacterial detection.

BACKGROUND: Pathogenic bacteria contribute to various globally important diseases, killing millions of people each year. Various fields of medicine currently benefit from or may potentially benefit from the use of nanotechnology applications, in which there is growing interest. Disease-related biomarkers can be rapidly and directly detected by nanostructures, such as nanowires, nanotubes, nanoparticles, cantilevers, microarrays, and nanoarrays, as part of an accurate process characterized by lower sample consumption and considerably higher sensitivity. There is a need for accurate techniques for pathogenic bacteria identification and detection to allow the prevention and management of pathogenic diseases and to assure food safety. CONCLUSION: The focus of this review is on the current nanoparticle-based techniques for pathogenic bacterial identification and detection using these applications.

The influence of circumferential resection margins on survival following rectal cancer surgery.

BACKGROUND AND AIMS: A negative (R0) circumferential resection margin (CRM) is described as one of the most important factor that decrease the rate of local recurrence in rectal cancer. The primary outcome of the study was the status of the CRM, while the secondary outcomes were local recurrence and overall survival. METHODS: Study includes 192 patients with rectal cancer operated between January 2012 and December 2013 in our Institute. The incidence of positive CRM and its impact on the survival rates after oncologic surgical resection were investigated along with factors that determine positive CRM. R1 was defined as a distance of ≤ 1 mm between the tumor and the resection margin. RESULTS: The R1 rate was 3.6 % (7 cases). Nine patients (4.68%) developed local recurrence during a median followup period of 720 days. A positive CRM was found to be a risk factor of local recurrence (p-value = 0.031) and it decreased the overall survival (p-value=0.001). pT4 stage (p-value=0.008) and vascular invasion (p-value=0.005) are factors that play significant roles in determining CRM positivity. In case of inferior rectal tumours abdomino-perineal resection (APR) determines significantly higher (p-value=0.048) rates of positive CRM than anterior resection (AR) of the rectum. CONCLUSIONS: Positive CRM affects overall survival and local recurrence in rectal cancer. pT4 stage and vascular invasion play determinant roles in determine CRM status. APR is a risk factor for positive CRM in inferior rectal tumors. KEY WORDS: Abdomino-perineal resection, Circumferential resection margins, Local recurrence, Rectal cancer, Overall survival.

Selective ex vivo photothermal nano-therapy of solid liver tumors mediated by albumin conjugated gold nanoparticles.

We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of BSA bound to GNPs into tumor cells following ex-vivo intra-vascular perfusion.

Selective in vitro photothermal nano-therapy of MRSA infections mediated by IgG conjugated gold nanoparticles.

There are serious systemic infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and several other types of bacteria leading to the deaths of millions of people globally. This type of mortality is generally caused by the increasing number of antibiotic-resistant organisms, a consequence of evolution via natural selection. After the synthesis of gold nanoparticles (GNPs) by wet chemistry, bio-functionalization with IgG molecules was performed. Following administration of IgG-GNPs to MRSA cultures at various concentrations and various incubation time laser irradiation was performed. To assess the selectivity and specificity of the proposed treatment the following methods were used: flow cytometry, contrast phase microscopy, and by fluorescence microscopy. The results in our study indicate that following administration of IgG-GNPs biomolecule an extended and selective bacterial death occurs following laser irradiation in a dose dependent manner. Therefore, the new findings might impel studies on these antibacterial nanomaterials and their biological and medical applications.

An atypical case of focal nodular hyperplasia. Problems of imagistic diagnosis.

Focal nodular hyperplasia (FNH) is a hepatic disease first described in 1958. The existence of an accessible and minimally invasive imagistic investigation to establish the diagnosis in a large number of cases would be desirable, especially because once diagnosed, the disease needs no treatment. We present the case of a young woman with long term use of oral contraceptives in which the diagnosis of FNH was established at a routine ultrasound. Evolution of disease during the pregnancy and the atypical imagistic aspect of liver lesions raised many problems of differential diagnosis.

Surface plasmon resonance-induced photoactivation of gold nanoparticles as mitochondria-targeted therapeutic agents for pancreatic cancer.

BACKGROUND: Noble metal nanoparticles such as gold nanoparticles can strongly absorb light in the visible region by inducing coherent collective oscillation of conduction band electrons in strong resonance with visible frequencies of light. This phenomenon is frequently termed as surface plasmon resonance (SPR). OBJECTIVES: The main objective was to study the effects of laser photoactivated gold nanoparticles (by means of SPR) on human pancreatic cancer cells. RESULTS: Gold nanoparticles obtained using standard wet chemical methods (with sodium borohydride as a reducing agent) underwent photoexcitation using 2w 808 nm laser and further administered to 1.4E7 pancreatic cancer cell lines. Flow cytometry, transmission electron microscopy, phase contrast microscopy, quantitative proteomics and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo excited gold nanoparticles and pancreatic cancer cells. CONCLUSION: The study shows that phonon-phonon interactions following laser photoexcitation of gold nanoparticles exhibit increased intracellular uptake, as well as mitochondrial swelling, closely followed by mitochondrial inner membrane permeabilization and depolarization. This unique data may represent a major step in mitochondria-targeted anticancer therapies using laser-activated gold nanoparticles.

Long term outcome following surgical treatment for distal gastric cancer.

BACKGROUND. At the current time, the belief that total gastrectomy (TG) offers a better survival benefit compared with distal gastrectomy (DG) in distal gastric cancer still persists among many surgeons. The aim of the study was to determine whether TG in patients with distal stomach cancer offers a benefit in long term survival compared with DG. METHODS. Data on 180 consecutive patients with adenocarcinoma of the distal stomach that underwent surgery during the period 2000-2003 were analyzed. Distal gastrectomy was performed on 91 patients (50.5%), and 89 patients (49.5%) underwent TG. RESULTS. The postoperative morbidity (anastomotic leakage, intraperitoneal hemorrhage and pulmonary complications) was significantly higher in the TG group than in the DG group. The TG group had a significantly higher rate of 30-day postoperative mortality than DG group, and a longer mean postoperative hospital stay. The 5-year survival rate was significantly higher for the DG group than for the TG group. The number of lymph node metastases and TNM stages are significant predictors of poor survival. CONCLUSIONS. Compared with patients undergoing TG, a better long-term survival time, lower postoperative morbidity and mortality rates and a lower hospitalization stay was obtained in patients that underwent DG for distal gastric cancer. This observation justifies the use of this procedure for the surgical therapy of the cancer of distal stomach.