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.

Multiple Pancreatic Metastasis of Clear Renal Cell Carcinoma Associated with Neuroendocrine Tumor.

Introduction: Metastatic tumors of the pancreas are uncommon, but renal cell carcinoma is one of the few known cancers that can metastasize to the pancreas. Few cases have been reported as being metachronous multicentric metastases to the pancreas, but none associated with a pancreatic neuroendocrine tumor and reported in literature, to our knowledge. Case presentation: We describe a case of 66-year-old woman who was diagnosed with multicentric pancreatic metastases from clear renal cell carcinoma associated with concomitant pancreatic neuroendocrine tumor, after 14 years from the initial diagnosis of kidney cancer. For this patient, the symptoms were unspecific for neoplastic disease, she had multiple pancreatic metastases which is an uncommon finding, but even rarer was the association of metastases with neuroendocrine tumor in the pancreas. Because of the good outcome and survival, surgical resection is recommended for solitary and multiple pancreatic metastases, as well as for pancreatic neuroendocrine tumors. Conclusion: Differential diagnosis for multiple pancreatic tumors is undisputedly important, even though it would not have changed anything in our patient's preoperatively course. Patients with renal cell carcinoma must follow long-term surveillance with regular examination and imaging investigation so that any possible metastases can be detected early and treated properly.

Spleen Preserving, Splenic Vessels Spearing, Pure Laparoscopic Total Duodenopancreatectomy for Intraductal Papillary Mucinous Pancreatic Neoplasia (IPMN): Case Report and Technique.

Total duodenopancreatectomy (TDP), performed exclusively by laparoscopic approach is considered one of the most complex abdominal surgical procedures. TDP with preservation of spleen vessels (operation Kimura) is a more technically-demanding procedure, but is beneficial in selected cases. While some high-volume centers have gained experience in minimally-invasive pancreatectomies, laparoscopic approach remains a recommendation for well selected patients with benign or low-grade malignant tumors and should be performed with caution, by experienced HPB surgeons. In this paper, we present a spleen preserving, splenic vessels spearing, pure laparoscopic TDP on a 40-year-old patient diagnosed with diffuse IPMN performed in our center, illustrating the operative steps.

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.

Abdominal Sepsis - Current Definitions and Practice.

Abdominal sepsis remains the second most common source of sepsis, a life-threatening condition that became a global health priority in the medical field research. Open abdomen is part of the damage control surgery, a life-saving strategy in a well-selected group of surgical patients with severe abdominal sepsis and intra-abdominal hypertension. Definitions and recommendations in the management of abdominal sepsis and open abdomen have gradually evolved, as a reflection of the progress of both the comprehension of physiopathological mechanisms involved in sepsis and the technology of different temporary abdominal closure systems. The aim of this paper is to make an up-to-date literature narrative review of the definitions and current practice guidelines in abdominal sepsis, with illustration of clinical experience in the management of open abdomen wounds. In the past decades, progress has been made in the management of abdominal sepsis, with greatly ameliorated survival rates. Rapid diagnosis, extensive comprehension of the physiopathological mechanisms of sepsis, adapted fluid resuscitation, antimicrobial therapy and damage-control surgery, orchestrated by a multy-disciplinary team, play an equally important role in the prognosis of a patient.

Laparoscopic Central Pancreatectomy with Pancreato-Gastric Anastomosis for Pancreatic Cystadenoma.

We present the case of a 42-year-old woman diagnosed with a cystic pancreatic lesion, suggestive of a serous cystadenoma of 27/13 mm. The diagnosis was established by the examination of abdominal CT and eco-endoscopy. The patient was referred to the surgery department for treatment. The benign etiology suggested by imaging and the desire to preserve the spleen along with as much of the pancreatic parenchyma, indicated a laparoscopic central pancreatectomy with a anastomosis between the distal pancreatic stump and the stomach. The authors reviewed the national and international publications related to the indications of this minimally invasive surgery.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis: Our Initial Experience.

Introduction: Peritoneal carcinomatosis represents an advanced stage of tumor dissemination of abdominal cancers in general and colorectal cancer in particular. The only therapeutic methods currently available for the treatment of this pathology are systemic chemotherapy (palliative character) and cytoreductive surgery (CR) with intraperitoneal chemotherapy. After evaluation of evidence-based medical literature and current guide lines we can state that CR + HIPEC procedure is considered to be the treatment of choice in case of patients with peritoneal carcinomatosis of colorectal, ovarian and mucinous appendicular origin. Material and method: In the present study we prospectively analyzed the immediate postoperative results obtained in the first 50 patients that were treated by our team for peritoneal carcinomatosis of different origin. We described the protocol of selection, the patients characteristics that were included in our CR+HIPEC program and analyzed the complications and death rate. Results: From January 2015 till Dec 2018 we evaluated 98 patients with peritoneal carcinomatosis. From them, 51 received radical CR+HIPEC treatment, 33 were not suitable for surgery because of the exclusion criteria's and 15 had only exploratory laparotomies. In regard with the histopathological diagnosis, 30 patients had ovarian cancer and 19 had colorectal cancer or peritoneal pseudomixoma of appendicular origin. There was no 30 days postoperative mortality. The incidence of significant postoperative complications was 15%. Conclusions: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is a complex technique accompanied by an acceptable rate of complications and postoperative deaths, the results being optimized by a standardized perioperative management and patient selection. The initial results obtained by our team emphasize the feasibility of this procedure, with immediate good results, as a result of a standardization protocol of patient selection and perioperative care.

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.

Assessing immunological surgical stress markers in patients undergoing digestive surgery for pancreatic, hepatic and gastric tumors.

PURPOSE: Cytokines like IL-6, IL-10 and other factors like CRP are involved in the postoperative inflammatory-stress response. The association between IL-6, IL-10, CRP, albumin and early postoperative complications and deaths was analyzed on a cohort of cancer patient. METHODS: The plasma levels of IL-6, IL-10 and serum levels of c-reactive protein (CRP) and albumin were measured in 85 patients undergoing surgical resection of pancreatic, hepatic and gastric tumors. The measurement of the studied biochemical parameters was made at three time points: before the operation, and on the 1st and 3rd day after the operation. RESULTS: Of the 85 patients, 28 suffered early postoperative complications (14 gastric cancer patients; 11 pancreatic cancer patients; 3 liver cancer patients) and 9 patients died in the early postoperative period (5 gastric cancer patients; 4 pancreatic cancer patients; 0 liver cancer patients). Patients with elevated levels of serum CRP on the 3rd postoperative day had a significant increased risk of death. Also, patients with higher levels of IL-10 on the 3rd postoperative day demonstrated a significantly increased risk of early postoperative complications. CONCLUSION: This study demonstrates that plasma IL-10 concentration is positively associated with postoperative complications.

Evaluation of P-POSSUM Risk Scoring System in Prediction of Morbidity and Mortality after Pancreaticoduodenectomy.

Background: POSSUM and P-POSSUM are risk scores recommended by ERAS Society for the preoperative evaluation of patients undergoing major surgery. Methods: This study includes 113 consecutive pancreaticoduodenectomy performed in a single centre between July 2013-December 2015. Patients data were prospectively collected using Excel 2009 and retrospectively analysed with R v3.2.4 software. Biological status score, surgical severity score and risk scores for complications and death were calculated using: http://www.riskprediction. org.uk/index-pp.php. Results: Morbidity rate was 61,95%: 19,47% general complications, 14,16% wound infections and 28,32% PD specific complications (11,5% POPF; 8,85% DGE and 6,19% PPH). Comparing the observed and estimated morbidity and mortality, we obtained statistical significant results (p=0,05 and p=0,03, respectivelly). When we considered only specific PD complications and subsequent mortality, there was no longer significant difference between observed and estimated values (p=0,8 and p=0,86).The under ROC curve aria was 0,61 for morbidity and 0,64 for specific PD morbidity, respectively 0,61 for mortality and 0,68 for specific PD complications related mortality. CONCLUSION: P-POSSUM represents a useful tool for appreciating the complication and death risk after PD, but better results could be obtain by considering also specific PD risk factors.

An Attempt to Build a National Prospective Electronic Database for Pancreaticoduodenectomies in Romania - Preliminary Results of the First Year Enrollment.

Introduction: National databases for pancreaticoduodenectomies (PD) have contributed to better postoperative outcomes after such complex surgical procedure because the multicentre collection of data allowed more reliable analyses with quality assessment and further improvement of technical issues and perioperative management. The current practice and outcomes after PD are poorly known in Romania because there was no national database for these patients. Thus, in 2016 a national-intent electronic registry for PD was proposed for all Romanian surgical centers. The study aims to present the preliminary results of this national-intent registry for PD after one-year enrollment. Patients Methods: The database was started on October 1st, 2016. Data were prospectively collected with an electronic online form including 102 items for each patient. The registry was opened to all the Departments of Surgery from Romania performing PD, with no restriction. Results: During the first year of enrollment were collected the data of 181 patients with PD performed by 24 surgeons from four surgical centers. The age of patients was 64 years (28 - 81 years), with slightly male predominance (61.3%). Computed tomography was the main preoperative imaging investigation (84.5%). All the PDs were performed by an open approach. The Whipple technique was used in 53% of patients, and a venous resection was required in 14.3% of cases. A posterior approach PD was considered in 16.6% of patients. The stomach was used to treat the distal remnant pancreas in 50.1% of patients. The operative time was 285 min (110 - 615 min), and the estimated blood loss was 400 ml (80 - 3000 ml). The overall morbidity rate was 55.8%, with severe (i.e., grade III-IV Dindo-Clavien) morbidity rate of 10%, and 3.9% in-hospital mortality rate. The overall pancreatic fistula, delayed gastric emptying and hemorrhage rates were 19.9%, 39.8% and 15.5%. Periampullary malignancies were the main indications for PD (78.9%), with pancreatic cancer on the top (48%). Conclusions: To build a prospective electronic online database for PD in Romania appears to be a feasible project and a useful tool to know the current practice and outcomes after PD in our country. However, improvements are still required to encourage a larger number of surgical centers to introduce the data of patients with PD.

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.

Harmonic Contrast-Enhanced Endoscopic Ultrasonography for the Guidance of Fine-Needle Aspiration in Solid Pancreatic Masses.

Purpose The global accuracy of fine-needle aspiration guided by endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85 %. The use of contrast agents during EUS to highlight vessels and the necrotic parts of pancreatic masses may improve biopsy guidance. Our aim was to assess whether the guidance of FNA by harmonic contrast-enhanced endoscopic ultrasound (CH-EUS) would increase diagnostic accuracy relative to conventional EUS-FNA in the same pancreatic masses. Patients and Methods In a prospective study, EUS-FNA was performed in patients with pancreatic masses on CT scan, followed by harmonic CH-EUS using SonoVue. A second cluster of CH-EUS-FNA was performed on contrast-enhanced images. The final diagnosis was based on the results of EUS-FNA and surgery, or the findings after 12 months' follow-up. Results The final diagnosis was adenocarcinoma (n = 35), chronic pancreatitis (n = 10), or other (n = 6). The diagnostic accuracy based on core histology was 78.4 % for EUS-FNA and 86.5 % for CH-EUS-FNA (p = 0.35). The accuracy increased to 94 % when the two methods' results were combined. The two false-negative EUS-FNA cases were correctly appreciated by CH-EUS. Neither core histology size nor the presence of necrosis was significant for the true-positive diagnosis of malignancy. Conclusion CH-EUS-FNA had an insignificant incremental effect on diagnostic accuracy compared with conventional EUS-FNA in our small group. The presence of necrosis did not influence the results of CEUS-FNA. Qualitative assessment of the contrast uptake within the lesion was useful in false-negative EUS-FNA cases.

Recent achievements in colorectal cancer diagnostic and therapy by the use of nanoparticles.

Colorectal cancer is a major public health issue, being the third most common cancer in men and the second in women. It is one of the leading causes of cancer deaths. Nanomedicine is an emerging field of interest, many of its aspects being linked to cancer research. Chemotherapy has a well-established role in colorectal cancer management, unfortunately being limited by inability to have a selective distribution, by multidrug resistance and adverse effects. Researches carried out in recent years about nanotechnologies aimed, among others, to resolve the issues mentioned above. Targeted and localized delivery of the chemotherapeutic drugs, using nanoparticles, with selective destruction of cancerous cells would minimize the toxicity on healthy tissues. Also, the use of nanomaterials as contrast agent could improve sensitivity and specificity of diagnosis. The purpose of this review is to highlight the recent achievements of cancer research by use of nanomaterials, in the idea of finding the ideal composite, capable to simultaneous diagnostic and treat cancer.

Rational design of gold nanocarrier for the delivery of JAG-1 peptide.

BACKGROUND: Unique properties exhibited by nanoparticles makes them great candidates for applications in physics, chemistry, biology, material science and medicine. The biological applications of water-soluble gold nanoparticles range from contrast agents, delivery vehicles to therapeutics. Notch signaling is a complex network that orchestrates cell fate decisions, which involves proliferation, migration, differentiation and cell death in organisms ranging from insects to humans. Studies have showed that a correct orientation of the Jag-1 signalling protein on the substrates proves to be of great importance when promoting Jagged-1 Notch interactions, also the availability of the ligands, super cedes the importance of their concentration. RESULTS: The aim of the present study was to synthetize a Jag-1 functionalized nanocarrier, which would promote an efficient interaction between the Jag-1 peptide and the Notch receptor. To this end, two routes for gold nanoparticle-peptide assembly were investigated, and the synthetized bio-nanostructures were characterized and compared by means of UV-Vis, FT-IR, DLS and AFM techniques. CONCLUSIONS: We have obtained a stable, monodisperse, hetero-functionalized GNP-PEG-JAG-1 bio-nanostructure for Notch pathway activation applications.

Laparoscopic rectal resection versus conventional open approach for rectal cancer - a 4-year experience of a single center.

PURPOSE: This study was carried out to compare the therapeutic outcomes and complications of the laparoscopic and the conventional open surgery technique used for treating rectal cancer. Another goal was to find the fastest and most accurate method of treatment for rectal cancer, along with establishing the advantages and disadvantages of the two surgical techniques, depending on cancer location and its stage. METHODS: A total of 172 patients diagnosed with rectal cancer and hospitalized in the Department of Surgery III between January 1st 2008 and December 31st 2011 were studied. The laparoscopic approach was performed on 29 (16.8%) patients, and the remaining 143 (83.2%) underwent the conventional Miles/Lloyd-Davies abdominoperineal resection. A longitudinal study was conducted on patients with rectal resection, the used data being obtained from the database of the Department of Surgery III, hospital records, protocols and clinical charts of rectal cancer cases. RESULTS: There were no statistically significant differences regarding symptoms, gender, age, body mass index (BMI), tumor site, TNM stage, intraoperative accidents, operative time, and postoperative mortality between the two groups. The laparoscopic group presented advantages regarding antibiotic and analgesic therapy, early mobilization, hospital stay, intraoperative blood loss, resuming oral nutrition, bowel transit resumption, postoperative complications and wound complications. CONCLUSION: Laparoscopic abdominoperineal resection for rectal cancer is feasible, safe and effective. It can be safely performed by an experienced team, reducing the rate of postoperative complications, the need for blood transfusions, the adminstration of antibiotics and painkillers, allowing faster bowel transit resumption, shortening hospital stay and providing superior aesthetic results.

Proteomic identification of potential prognostic biomarkers in resectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is a devastating disease with a mortality rate almost identical with its incidence. In this context, the investigation of the pancreatic cancer proteome has gained considerable attention because profiles of proteins may be able to identify disease states and progression more accurately. Therefore, our objective was to investigate the changes in the proteome of patients suffering from pancreatic ductal adenocarcinoma (PDAC) by a comprehensive quantitative approach. Comparative proteomic profiling by label-free LC-MS/MS analysis of nine matched pairs of tumor and nontumor pancreas samples was used to identify differences in protein levels characteristic for PDAC. In this analysis, 488 proteins were quantified by at least two peptides of which 99 proteins displayed altered levels in PDAC (p < 0.01, fold change >1.3). Screening of data revealed a number of molecules that had already been related to PDAC such as galectin-1 (LEG1), major vault protein, adenylyl cyclase-associated protein 1 (CAP1), but also a potential new prognostic biomarker prolargin (PRELP). The Kaplan-Meier survival analysis revealed a significant correlation of protein abundance of PRELP with postoperative survival of patients with PDAC. For selected proteins the findings were verified by targeted proteomics (SRM), validated by immunohistochemistry and Western blotting and their value as candidate biomarkers is discussed.

Microscopic Positive Margins in Gastric Adenocarcinoma Following Oncological Resection: Prognostic Factors and Long-Term Survival.

BACKGROUND: In the context of gastric cancer, surgical resection stands as the sole curative treatment. Central to influencing overall survival are the resection margins. This research aims to identify the factors influential in determining microscopically positive resection margins (R1) and to evaluate overall survival. METHODS: Our study encompassed 549 patients diagnosed with adenocarcinoma of the stomach who underwent curative-intent surgery between January 2011 and December 2021 in our Surgery Department. We investigated the incidence of positive margins (R1) and their impact on survival rates, as well as the determinants of R1. The standardization of R1 involved ensuring a margin distance of less than 1 mm from the tumor line to the margin. RESULTS: The incidence of R1 margins was 13.29% (73 patients). Among these, proximal R1 margins were observed in 29 patients (39.72%), while 49 cases (67.12%) presented circumferentially positive margins, with 20 cases (27.39%) exhibiting distally positive margins. Nineteen patients (26.02%) had two R1 margins, and 3 patients had all resection margins microscopically positive (4.10%). Factors such as tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading demonstrated significance (p < 0.01) in the occurrence of positive R1 margins. CONCLUSION: Tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading could be regarded as factors for predicting microscopically positive margins. Moreover, positive resection margins have a detrimental impact on overall survival.

Open or laparoscopic treatment for hydatid disease of the liver? A 10-year single-institution experience.

BACKGROUND: Selection of the most appropriate treatment to obtain the lowest morbidity, mortality, and recurrence rates is mandatory for hydatid disease of the liver. This study evaluated the results of laparoscopic treatment (compared with the open approach) in the context of a 10-year single-institution experience. METHODS: Between January 1998 and January 2008, 333 patients with hydatid disease of the liver underwent surgery in the authors' department. Only the following aspects were considered as selection criteria for laparoscopic surgery: liver cyst not located in segment 1 or 7, with corticalization on the surface and no evidence of intrabiliary rupture. Of 62 patients who underwent laparoscopic treatment, 3 required conversion to open surgery. The remaining 59 patients (group 1) were analyzed. During the same period, 271 patients with hepatic hydatid disease underwent conventional surgery, but only 172 records were compatible with the criteria for the laparoscopic approach and the respective patients were retrospectively reviewed (group 2). RESULTS: Conversion to open surgery occurred in three cases (4.84 %). The mean cyst diameter was 6.62 cm (range, 2-15 cm) in group 1 and 7.23 cm (range, 2-18 cm) in group 2 (p = 0.699). The mean operative time was 72 min (range, 45-140 min) in group 1 and 65 min (range, 35-120 min) in group 2 (p < 0.001). The general complication rate and abdominal wound complication rate were respectively 0 % and 0 % in group 1 (p = 0.023) compared with 5.23 and 8.72 % in group 2 (p = 0.015). The mean hospital stay was 6.42 days (range, 1-21 days) in group 1 and 11.7 days (range, 4-80 days) in group 2 (p < 0.001). The mean follow-up period was 24.2 months (range, 6-32 months) in group 1 and 28.4 months (range, 6-40 months) in group 2. No recurrences were observed in either group during this period. CONCLUSION: Laparoscopic surgery provides a safe and efficacious approach for almost all types of hepatic hydatid cysts. Large, prospective, randomized trials are needed to confirm its superiority.