Current Surgical Concepts and Future Perspectives in the Treatment of Borderline Resectable and Potentially Resectable Locally Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents an aggressive tumor with a low five-year survival rate of less than 10%. Only 20% of patients are estimated to be eligible for upfront curative resection at the time of presentation. The larger group of borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) had much poorer outcomes in the past. Although there are improvements for the multimodal therapy of PDAC, surgery remains the single hope for a cure. Combined with adjuvant and/ or neoadjuvant treatment, pancreatic surgery can enhance five-year survival by up to 20%. However, pancreatic resection is widely associated with a high risk of complications and is regarded as one of the most complex surgical procedures. TRIANGLE operation should be added to pancreatic surgery armamentarium as a key procedure, with the potential to increase the number of harvested lymph nodes, reduce the complications rate, and better radical treatment efficacy for BRPC and LAPC be converted to resectability after neoadjuvant treatment (NAT). More and more aggressive pancreatectomy has become justified in the context of NAT. Further technical standardization and optimal neoadjuvant strategy are mandatory for the global dissemination of aggressive pancreatectomies. This review summarizes the surgical treatment for BRPC and potentially resectable LAPC based on the current literature, focusing on the "TRIANGLE "concept of pancreatic surgery.

Significance of Biomarkers in Early Diagnosis of Abdominal Sepsis.

INTRODUCTION/OBJECTIVE: Peritonitis is one of the most important sources of abdominal sepsis. Since intra-abdominal infection leads to the activation of the inflammatory response, this suggested that some of these mediators could be used as markers of the severity of newly formed sepsis, but primarily to identify or rule out new-onset sepsis. The aim of this study was to evaluate the sensitivity and specificity of serum markers of inflammation: C-reactive protein, procalcitonin and serum amyloid A in the serum of patients with diffuse secondary peritonitis. Methods: The prospective cohort study was conducted at the Clinic for Emergency Surgery of the Clinical Center of Serbia in Belgrade. The study group consisted of 100 patients aged 18 to 70 years, with signs of acute abdomen due to diffuse secondary peritonitis. Results: CRP and PCT are so far among the most valuable preoperative markers for distinguishing sepsis from SIRS. On the first postoperative day the analysis of the relationship between sensitivity and specificity at the different breakpoints used indicates a greater diagnostic accuracy and greater sensitivity of SAA compared to CRP and PCT. In the remaining postoperative period in our study, the ROC curve mostly coincided with the diagonal line, so CRP, PCT, and SAA had little diagnostic accuracy. CONCLUSION: The results of our study suggest that finding a specific marker for the diagnosis of abdominal sepsis, a marker that would differentiate between SIRS and sepsis, pre- and postoperatively, would be very useful.

Is Colorectal Cancer Stage Affected by COVID-19 Pandemic?

Background: Causing healthcare systems overload, COVID-19 pandemic has a huge influence on patients with colorectal cancer. The aim of our study was to assess the potential impact of COVID-19 on the stage of colorectal cancer. Methods: In our retrospective study, two groups of patients operated for colorectal cancer were analyzed at the Clinic for Surgery "Nikola Spasic", Zvezdara University Medical Center. The study group consisted of 49 patients operated in the period from March 15, 2020 to April 2021, during COVID-19 pandemic. The control group consisted of 152 patients, who were operated on in the period from January 1, 2019. to December 31, 2019. Results: There were no difference in surgical approach, prevalence of stoma, percentages of postoperative complications and rates of hospital readmission between both groups. T4b tumor stage was statistically significant more common in the study group (12.2% vs 3.3%, p=0.027). Locally advanced tumors, stage IIC, were statistically significantly more common in the group of patients operated on during the COVID-19 pandemic (10.2% vs 1.3%, p=0.01). Conclusion: Higher number of locally advanced tumors in study group could probably be caused by the impact of the COVID-19 pandemic on healthcare system.

Mortality predictors of patients suffering of acute pancreatitis and development of intraabdominal hypertension

Background/aim: Intraabdominal hypertension (IAH) occurs frequently in patients with acute pancreatitis and adds to their morbidity and mortality. The main aim of the study was to identify the determination of the predictive factors connected to IAH that influence the evolution of acute pancreatitis. Materials and methods: The prospective cohort study was conducted on 100 patients who had acute pancreatitis. According to obtained intraabdominal pressure (IAP) values, the patients were divided into two groups: one group (n = 40) with normal IAP values and the other (IAH group, n = 60) with increased IAP values. Deceased patients were specially analyzed within the IAH group in order to determine mortality predictors. Results: Statistical significance of IAP (P = 0.048), lactates (P = 0.048), peak pressure (P = 0.043), abdominal perfusion pressure (P = 0.05), and mean arterial pressure (P = 0.041) was greater for deceased than for surviving patients in the IAH group. High mortality appears for patients younger than 65 years old, with lactate level higher than 3.22 mmol/L and filtration gradient (GF) lower than 67 mmHg. Conclusion: Age, lactates, GF, and APACHE II score are determined as mortality predictors for patients suffering from acute pancreatitis who developed IAH. The mortality rate is higher when the level of GF is decreasing and the level of lactate increasing.

Twenty-Eight-Day Mortality of Blunt Traumatic Brain Injury and Co-Injuries Requiring Mechanical Ventilation.

OBJECTIVE: This paper aims to assess the impact of co-injuries and consequent emergency surgical interventions and nosocomial pneumonia on the 28-day mortality of patients with severe traumatic brain injuries (TBIs). SUBJECTS AND METHODS: One hundred and seventy-seven patients with TBI admitted to the emergency trauma intensive care unit at the Clinical Center of Serbia for more than 48 h were studied over a 1-year period. On admission, the Glasgow Coma Scale (GCS), Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation II score (APACHE II) were calculated. At admission, an isolated TBI was recorded in 45 of the patients, while 44 had three or more co-injuries. RESULTS: Of the 177 patients, 78 (44.1%) died by the end of the 28-day follow-up period. They had a significantly higher ISS score (25 vs. 20; p = 0.024) and more severe head (p = 0.034) and chest (p = 0.013) injuries compared to those who survived. Nonsurvivors had spent more days on mechanical ventilation (9.5 vs. 8; p = 0.041) and had a significantly higher incidence of ventilator-associated pneumonia (VAP) than survivors (67.9 vs. 40.4%; p < 0.001). A high Rotterdam CT score (OR 2.062; p < 0.001) and a high APACHE II score (OR 1.219; p < 0.001) were identified as independent predictors of early TBI-related mortality. CONCLUSION: Patients who had TBI with a high Rotterdam score and a high APACHE II score were at higher risk of 28-day mortality. VAP was a very common complication of TBI and was associated with an early death and higher mortality in the subgroup of patients with a GCS ≤8.

Interleukin-12 as a predictor of outcome in patients with severe acute pancreatitis.

BACKGROUND/AIMS: The aim of this study was to determine the role of serum Interleukin-12 level as early marker of severity of the SAP and correlation between IL12, SIRS score, APACHE II and Ranson score in prediction of illness severity as well as of outcome of SAP. METHODOLOGY: We evaluated a total of 234 patients with first onset of SAP, appears in last 24 hours, admitted in surgical Intensive care unit (ICU). Severe Acute Pancreatitis was diagnosed with an APACHE II score of 8 or higher, and/or a Ranson score of 3 or higher, and/or Balthazar scores of 5 or higher. Serum IL-12 concentrations were measured with a commercially aviable IL-12 kit, on admission and days 3, 7, and 14. RESULTS: IL-12 concentration was significantly higher at 24h compared with IL-12 levels at admission (P = 0.010) and after 72h (P = 0.005). IL-12 concentrations significantly correlated with IL-6 concentrations (r = 0.209, P < 0.001), IL-8 concentrations (r = 0.527, P < 0.001), IL-10 concentrations (r = 0.552, P < 0.001), interpheron-gamma (r = 0.740, P < 0.001), TNF-alpha (r = 0.088, P < 0.05), C-reactive protein (r = -0.097, P < 0.001), in-hospital death (r = -0.171, P < 0.001), APACHE II score (r = 0.140, P < 0.001), and Ranson score (r = -0.319, P < 0.001). CONCLUSIONS: The serum values of the IL-12 can be used as an early marker of severity and course of SAP.

Suprahilar vascular control and stapling device transection of Glissonian pedicle in major and minor hepatectomies.

BACKGROUND/AIMS: In this study we analyzed our experience of suprahilar-posterior intrahepatic Glissonian pedicle approach using an endo-GIA vascular stapling device for the pedicle and hepatic vein division. METHODOLOGY: Sixty-eight 68 major and 102 minor liver resections were performed. The hilar extrahepatic structures remain intact, and during parenchyma dissection by CUSA, the whole right or left or the appropriate segmental pedicle was isolated intrahepatically and then transected using a stapler device. RESULTS: The minor liver resections was associated with significantly shorter surgery duration (95.1 + 31.1 vs. 186.6 +/- 56.5) and transection time (35.9 +/- 14.5 vs. 65.3 +/- 17.2) than major hepatectomies (p < 0.001 for all). The mean blood loss was 255.6 + 129.9 mL in minor resection and 385.7 + 200.1 mL in major resection (p = 0.003). The mean blood transfusion requirement was 300.8 + 99.5 mL for the patients with minor hepatectomy and 450.9 + 89.6 mL for those with major liver resection (p = 0.067). There was no significant difference in morbidity and mortality between the groups (p = 0.989; p = 0.920). Major as well as minor liver resection were a superior oncologic operation with no significant difference in the 3-year overall survival rates. CONCLUSIONS: Liver transection using CUSA with suprahilar endo-GIA stapling of Glisson's pedicle, as well as major hepatic veins represents an effective and safe surgical procedure.

Prognostic Value of Combined Hematological/Biochemical Indexes and Tumor Clinicopathologic Features in Colorectal Cancer Patients-A Pilot Single Center Study.

Colorectal cancer (CRC) is a significant public health problem. There is increasing evidence that the host's immune response and nutritional status play a role in the development and progression of cancer. The aim of our study was to examine the prognostic value of clinical markers/indexes of inflammation, nutritional and pathohistological status in relation to overall survival and disease free-survival in CRC. The total number of CRC patients included in the study was 111 and they underwent laboratory analyses within a week before surgery. Detailed pathohistological analysis and laboratory parameters were part of the standard hospital pre-operative procedure. Medical data were collected from archived hospital data. Data on the exact date of death were obtained by inspecting the death registers for the territory of the Republic of Serbia. All parameters were analyzed in relation to the overall survival and survival period without disease relapse. The follow-up median was 42 (24-48) months. The patients with the III, IV and V degrees of the Clavien-Dindo classification had 2.609 (HR: 2.609; 95% CI: 1.437-4.737; p = 0.002) times higher risk of death. The modified Glasgow prognostic score (mGPS) 2 and higher lymph node ratio carried a 2.188 (HR: 2.188; 95% CI: 1.413-3.387; p < 0.001) and 6.862 (HR: 6.862; 95% CI: 1.635-28.808; p = 0.009) times higher risk of death in the postoperative period, respectively; the risk was 3.089 times higher (HR: 3.089; 95% CI: 1.447-6.593; p = 0.004) in patients with verified tumor deposits. The patients with tumor deposits had 1.888 (HR: 1.888; 95% CI: 1024-3481; p = 0.042) and 3.049 (HR: 3.049; 95% CI: 1.206-7.706; p = 0.018) times higher risk of disease recurrence, respectively. The emphasized peritumoral lymphocyte response reduced the risk of recurrence by 61% (HR: 0.391; 95% CI: 0.196-0.780; p = 0.005). Standard perioperative laboratory and pathohistological parameters, which do not present any additional cost for the health system, may provide information on the CRC patient outcome and lay the groundwork for a larger prospective examination.

The efficacy of three transection techniques of the liver resection: a randomized clinical trial.

BACKGROUND/AIMS: Liver resection is a demanding procedure due to the risk of massive blood loss. Different instruments for liver transection are available today. The aim of this randomized clinical trial was to analyze the efficacy of three different parenchyma transection techniques of liver resection. METHODOLOGY: A total of 60 non-cirrhotic patients undergoing hepatectomy were randomly selected for clamp crushing technique (CRUSH), ultrasonic dissection (CUSA) or bipolar device (LigaSure), n=20 in each group. All patients had liver resection under low central venous pressure anaesthesia (CVP), with ischemic preconditioning and intermittent inflow occlusion. Primary endpoints were surgery duration, transection duration, cumulative pedicle clamping time, intraoperative blood loss and blood transfusion. Secondary endpoints included the postoperative liver injury, postoperative morbidity and mortality. RESULTS: Overall surgery duration was 295 vs. 270 vs. 240min for LigaSure, CUSA and Clamp Crushing Technique, respectively. The transection duration was 85 vs. 52.5 vs. 40 minutes, respectively. These three different resection techniques of non-cirrhotic liver produced similar outcome in terms of intraoperative blood loss, blood transfusion, postoperative complications and mortality. CONCLUSIONS: The Clump Crushing Technique, CUSA and Liga Sure are equally safe for resection of non-cirrhotic liver. Liver resections can be performed safely if the entire concept is well designed and the choice of dissection device does not affect the outcome of hepatectomy.

Glissonean pedicle approach in major liver resections.

BACKGROUND/AIMS: Liver resections are still one of the most challenging operations. The aim of this study was to analyze the efficiency and safety of the intrahepatic Glissonean pedicle approach vs. classical Hilar dissection in major hepatectomies. METHODOLOGY: Thirty-four patients were assigned to the Glissonean approach (GA, n=34), while the Hilar dissection were assessed as historical control, matched for the age, gender, comorbidities and Child-Pugh score (HD, n=34). RESULTS: The GA was associated with significantly shorter surgery duration (191.18±41.10 vs. 246.62± 56.55), transection time (38.94±14.56 vs. 56.32±19.40) and ischemic duration (26.03±11.27 vs. 41.18±12.80) than HD (p<0.001 for all). The amount of blood loss was significantly lower in GA (245.59±169.39 vs. 344.71±166.25; p=0.018). The amount of blood transfusion was significantly lower in GA during surgery (322.86±102.07 vs. 414.76±135.48) as well as postoperatively than HD (246.67±5.77 vs. 336.67±120.55) (p=0.038 and p=0.026. respectively). CONCLUSIONS: Major hepatectomy can be performed more easily using the Glissonean pedicle approach than by hilar dissection. En-masse transection of pedicles, as well as hepatic veins, using endo-GIA vascular stapler could be performed safely. Liver surgeons should know the Glissonean pedicle approach.

WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections.

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

Nonfunctional retroperitoneal paraganglioma presenting as acute upper gastrointestinal hemorrhage.

Paragangliomas are very rare tumors arising from extraadrenal chromaffin cells. Clinical presentation of benign retroperitoneal nonfunctional paraganglioma is unspecific. Symptoms may occur when tumor attains a remarkable size or when complications arise. This article reports a case of nonfunctional retroperitoneal paraganglioma as a cause of acute upper gastrointestinal hemorrhage which represents the unusual urgent clinical manifestation of these tumors. The presented case emphasizes the necessity to include extraadrenal paraganglioma in the differential diagnosis in all patients with retroperitoneal mass found even in the presence of at first appearance non-related emergency condition like acute upper gastrointestinal bleeding.

Prospective evaluation of the prevalence of Helicobacter pylori in abdominal surgery patients.

BACKGROUND/AIMS: Helicobacter pylori infection is accepted to be associated with two mutually exclusive diseases duodenal ulcer and gastric cancer. The aim of this study was to explore the relationship and prevalence of Helicobacter pylori infection in different surgical diseases. METHODOLOGY: With use of simple serologic assays for detecting IgA and IgG antibodies to HP antigen, we studied the association of infection with HP and 15 surgical diseases. RESULTS: The prevalence of HP was 68.60% (results of assays were positive for 142 patients out of 207). This study confirmed statistically significant correlation between HP seropositivity and pancreatic cancer (p = 0.02), hepatocellular cancer (p = 0.000), gastric cancer (p = 0.01), colon cancer (p = 0.002), rectal cancer (p = 0.001), intestinal cancer (p = 0.026), stenosis pylori (p = 0.01), ulcer diseases (p = 0.004), jaundice (p = 0.002); statistically significant inverse association between HP seropositivity and the acute appendicitis (p = 0.013) and no correlation with HP infection and cholecystitis (p = 0.716), cholelithiasis (p = 0.06), and ulcer hemorrhage (p = 0.064). CONCLUSION: The use of simple serological tests to identify patients with HP infection could help to calculate the risk of development of severe gastrointestinal diseases.

SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

BACKGROUND/AIMS: Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). METHODOLOGY: We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. RESULTS: In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. CONCLUSION: The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting.

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of acute left-sided colonic diverticulitis (ALCD) according to the most recent available literature. The update includes recent changes introduced in the management of ALCD. The new update has been further integrated with advances in acute right-sided colonic diverticulitis (ARCD) that is more common than ALCD in select regions of the world.

Laser-induced damages of different types of human gallbladder stones.

BACKGROUND/AIMS: Today, treatment of human calculi, and particularly those of gallbladder, is, to a large extent, less invasive procedure due to numerous non-invasive methods that have been developed. METHODOLOGY: CO2 laser of pulse (output 5W)(W-watt, SI unit system) and continual mode (output 15W) and diode laser (808 nm-nanometer, SI) were used for tests of fragmentation of gallbladder calculi in vitro. RESULTS: A total of 15 human gallbladder calculi of known size were examined, which had been collected during surgical interventions. Damages caused by laser were examined visually and by stereomicroscope (10 to 25 times magnification). During testing, the dependence of fragmentation on the type of laser effect, as well as the degree of fragmentation on the type of tested calculus was noted. Different types and dimensions of damage caused by various laser beams, as well as coloration changes of superficial layers in relation to the type of tested calculi was noticed. CONCLUSION: Accordingly, in this specific case, the priority for removal of gallbladder calculi by ablation will be given to diode laser.

Altered cytokine expression in Helicobacter pylori infected patients with bleeding duodenal ulcer.

OBJECTIVE: Peptic ulcer disease is a condition in which an important role has infection with H. pylori. The most common complication of peptic ulcer is bleeding. The presence of H. pylori triggers local and systemic cytokine signaling which may affect processes such as healing, gastric or duodenal rupture, and carcinogenesis. In this study, we examined the concentrations of IL-1ß, IL-6, IL-10, TNF, TGF-ß and IL-17A in serum by enzyme immunoassay and their mRNA expressions in periulcer biopsies obtained from patients with bleeding peptic ulcer by means of real-time-PCR. RESULTS: We have shown that pro-inflammatory IL-6 and TNF concentrations in serum were significantly higher in patients who were infected with H. pylori, while the concentrations of TGF-ß and IL-17A were significantly lower compared to non-infected subjects. IL-17A expression in periulcer mucosa was significantly higher in patients who were infected with H. pylori, while the expression of other cytokines, there was no significant difference compared to non-infected controls. Considering higher serum concentrations in non-infected subjects and higher IL-17A expression in mucosal tissue of infected patients, our data support the studies that found IL-17A has protective role in eradication of H. pylori infection in infected patients.

2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

Procalcitonin in preoperative diagnosis of abdominal sepsis.

BACKGROUND AND AIMS: The present study attempted to identify the diagnostic significance of procalcitonin (PCT) in acute abdominal conditions as well as the range of concentrations relating to diagnosis of abdominal sepsis. MATERIALS AND METHODS: This was prospective clinical study. The study included 98 consecutive patients with acute abdominal conditions, divided in sepsis and systemic inflammatory response syndrome (SIRS) group. RESULTS: PCT concentrations on admission were significantly higher in the sepsis group than in the SIRS group (median [interquartile range] 2.32 [7.41] vs 0.45 ng/ml [2.62]). A cutoff value of 1.1 ng/ml yielded 72.4% sensitivity and 62.5% specificity. In a group of patients with abdominal symptoms lasting for more than 24 h, a cut-off value of 1.1 ng/ml yielded higher sensitivity (82.9%) and higher specificity (77.3%). CONCLUSION: Our results suggest that PCT measurements may be useful for early, preoperative diagnosis of abdominal sepsis.