Toward a new paradigm of care: a surgical leaders' Delphi consensus on the organizational factors of the new pancreas units (E-AHPBA PUECOF study).

Pancreas units represent new organizational models of care that are now at the center of the European debate. The PUECOF study, endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), aims to reach an expert consensus by enquiring surgical leaders about the Pancreas Units' most relevant organizational factors, with 30 surgical leaders from 14 countries participating in the Delphi survey. Results underline that surgeons believe in the need to organize multidisciplinary meetings, nurture team leadership, and create metrics. Clinical professionals and patients are considered the most relevant stakeholders, while the debate is open when considering different subjects like industry leaders and patient associations. Non-technical skills such as ethics, teamwork, professionalism, and leadership are highly considered, with mentoring, clinical cases, and training as the most appreciated facilitating factors. Surgeons show trust in functional leaders, key performance indicators, and the facilitating role played by nurse navigators and case managers. Pancreas units have a high potential to improve patients' outcomes. While the pancreas unit model of care will not change the technical content of pancreatic surgery, it may bring surgeons several benefits, including more cases, professional development, easier coordination, less stress, and opportunities to create fruitful connections with research institutions and industry leaders.

Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure: A systematic review.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is one of the main causes of postoperative mortality and is challenging to predict early in patients after liver resection. Some studies suggest that the postoperative serum phosphorus might predict outcomes in these patients. AIM: To perform a systematic literature review on hypophosphatemia and evaluate it as a prognostic factor for PHLF and overall morbidity. METHODS: This systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses statement. A study protocol for the review was registered in the International Prospective Register of Systematic Reviews database. PubMed, Cochrane and Lippincott Williams & Wilkins databases were systematically searched up to March 31, 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for PHLF, overall postoperative morbidity and liver regeneration. The quality assessment of the included cohort studies was performed according to the Newcastle-Ottawa Scale. RESULTS: After final assessment, nine studies (eight retrospective and one prospective cohort study) with 1677 patients were included in the systematic review. All selected studies scored ≥ 6 points according to the Newcastle-Ottawa Scale. Cutoff values of hypophosphatemia varied from < 1 mg/dL to ≤ 2.5 mg/dL in selected studies with ≤ 2.5 mg/dL being the most used defining value. Five studies analyzed PHLF, while the remaining four analyzed overall complications as a main outcome associated with hypophosphatemia. Only two of the selected studies analyzed postoperative liver regeneration, with reported better postoperative liver regeneration in cases of postoperative hypophosphatemia. In three studies hypophosphatemia was associated with better postoperative outcomes, while six studies revealed hypophosphatemia as a predictive factor for worse patient outcomes. CONCLUSION: Changes of the postoperative serum phosphorus level might be useful for predicting outcomes after liver resection. However, routine measurement of perioperative serum phosphorus levels remains questionable and should be evaluated individually.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Measuring Perfusion in Pancreatic Ductal Adenocarcinoma and Different Tumor Grade: A Preliminary Single Center Study.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging is a noninvasive imaging modality that can supply information regarding the tumor anatomy and physiology. The aim of the study was to analyze DCE-MRI perfusion parameters in normal pancreatic parenchymal tissue and PDAC and to evaluate the efficacy of this diagnostic modality in determining the tumor grade. METHODS: A single-center retrospective study was performed. A total of 28 patients with histologically proven PDAC underwent DCE-MRI; the control group enrolled 14 patients with normal pancreatic parenchymal tissue; the radiological findings were compared with histopathological data. The study patients were further grouped according to the differentiation grade (G value): well- and moderately differentiated and poorly differentiated PDAC. RESULTS: The median values of Ktrans, kep and iAUC were calculated lower in PDAC compared with the normal pancreatic parenchymal tissue (p < 0.05). The mean value of Ve was higher in PDAC, compared with the normal pancreatic tissue (p < 0.05). Ktrans, kep and iAUC were lower in poorly differentiated PDAC, whereas Ve showed no differences between groups. CONCLUSIONS: Ve and iAUC DCE-MRI perfusion parameters are important as independent diagnostic criteria predicting the probability of PDAC; the Ktrans and iAUC DCE-MRI perfusion parameters may serve as effective independent prognosticators preoperatively identifying poorly differentiated PDAC.

DNA Methylation of HOXA11 Gene as Prognostic Molecular Marker in Human Gastric Adenocarcinoma.

Hypermethylation of tumor suppressor genes and hypomethylation of oncogenes might be identified as possible biomarkers in gastric cancer (GC). We aimed to assess the DNA methylation status of selected genes in GC tissue samples and evaluate these genes' prognostic importance on patient survival. Patients (99) diagnosed with GC and who underwent gastrectomy were included. We selected a group of genes (RAD51B, GFRA3, AKR7A3, HOXA11, TUSC3, FLI1, SEZ6L, GLDC, NDRG) which may be considered as potential tumor suppressor genes and oncogenes. Methylation of the HOXA11 gene promoter was significantly more frequent in GC tumor tissue (p = 0.006) than in healthy gastric mucosa. The probability of surviving longer (71.2 months (95% CI 57-85.3) vs. 44.3 months (95% CI 34.8-53.9)) was observed with unmethylated HOXA11 promoter in cancer tissues. Survival in patients with a methylation of HOXA11 promoter either in healthy gastric mucosa or gastric cancer tissue was twice as high as in patients with a methylation of HOXA11 promoter in both healthy gastric mucosa and cancer tissue (61.2 months (95% CI 50.9-71.4) vs. 28.5 months (95% CI 20.8-36.2)). Multivariate Cox analysis revealed the HOXA11 methylation as significantly associated with patients' survival (HR = 2.4, 95% CI 1.19-4.86). Our results suggest that the HOXA11 gene might be a potential prognostic molecular marker in patients with gastric adenocarcinoma.

Structural imaging findings are related to clinical complications in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Structural pancreatic changes and complications related to chronic pancreatitis are well described, but little is known about their relationship. We aimed to explore the associations between pancreatic morphology and clinical complications in a large chronic pancreatitis cohort. METHODS: The Scandinavian Baltic Pancreatic Club database collects registrations on patients with definite or probable chronic pancreatitis according to the M-ANNHEIM diagnostic criteria. In this cross-sectional study, we used multivariate logistic regression analyses to evaluate whether imaging-based structural pancreatic changes were associated with common clinical complications. We adjusted for sex, age, disease duration, current alcohol abuse and current smoking. RESULTS: We included 742 patients with a mean age of 55 years. Among these, 68% were males, 69% had pancreatic exocrine insufficiency, 35% had diabetes, 12% were underweighted and 68% reported abdominal pain. Main pancreatic duct obstruction, severe (i.e. more than 14) calcifications, pancreatic atrophy and parenchymal changes throughout the entire pancreas (continuous organ involvement) were positively associated with pancreatic exocrine insufficiency. Continuous organ involvement and pseudocysts were positively and negatively associated with diabetes, respectively. Pancreatic atrophy and severe calcifications were positively associated with underweight, and severe calcifications were negatively associated with pain. CONCLUSIONS: This study shows independent associations between distinct structural changes on pancreatic imaging and clinical complications in chronic pancreatitis. Pancreatic atrophy, severe calcifications and continuous organ involvement may be of particular clinical relevance, and these findings should motivate monitoring of pancreatic function and nutritional status.

Dynamic perfusion CT - A promising tool to diagnose pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVE: This study deals with an important issue of setting the role and value of the dynamic computed tomography (CT) perfusion analysis in diagnosing pancreatic ductal adenocarcinoma (PDAC). The study aimed to assess the efficacy of perfusion CT in identifying PDAC, even isodense or hardly depicted in conventional multidetector computed tomography. METHODS: A total of 56 patients with PDAC and 56 control group patients were evaluated in this study. A local perfusion assessment, involving the main perfusion parameters, was evaluated for all the patients. Sensitivity, specificity, positive, and negative predictive values for each perfusion CT parameter were defined using cutoff values calculated using receiver operating characteristic curve analysis. We accomplished logistic regression to identify the probability of PDAC. RESULTS: Blood flow (BF) and blood volume (BV) values were significant independent diagnostic criteria for the presence of PDAC. If both values exceed the determined cutoff point, the estimated probability for the presence of PDAC was 97.69%. CONCLUSIONS: Basic CT perfusion parameters are valuable in providing the radiological diagnosis of PDAC. The estimated BF and BV parameters may serve as independent diagnostic criteria predicting the probability of PDAC.

Dynamic Perfusion Computed Tomography and Apparent Diffusion Coefficient as Potential Markers for Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: Tumor grade, one of the most important risk factors for survival, is routinely determined after examining the biopsy material or a surgically removed specimen. The aim of the study was to analyze computed tomography (CT) perfusion parameters and diffusion-weighted imaging apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and to establish the diagnostic value of these modalities determining the tumor grade. MATERIALS AND METHODS: A prospective clinical study included 56 subjects with PDAC. All the patients had a local perfusion assessment and ADC measurement of the tumor. For the prediction of poor tumor differentiation sensitivity, specificity, positive, and negative predictive values for each perfusion CT and ADC parameters based on cutoff values from ROC analysis were calculated. RESULTS: Mean transit time (MTT) and ADC values were found to be independent prognosticators for the presence of G3 PDAC. MTT and ADC at the cutoff of 17.37 s and 1.15 × 10-3 mm2/s, respectively, appeared to be significant parameters discriminating against the differentiation grade of PDAC. If both values exceeded the defined cutoff point, the estimated probability for the presence of G3 PDAC was 89.29%. CONCLUSION: The MTT parameter, calculated with the deconvolution method, and the ADC value may serve as effective independent prognosticators identifying poorly differentiated PDAC.

Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

BACKGROUND AND OBJECTIVES: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients. METHODS: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores. RESULTS: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status. CONCLUSIONS: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification.

Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?

OBJECTIVE: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. SUMMARY/BACKGROUND: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. METHODS: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. RESULTS: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. CONCLUSIONS: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Epigenetic Regulation of APAF-1 Through DNA Methylation in Pancreatic Cancer.

BACKGROUND/AIM: Apoptotic peptidase activating factor 1 (APAF-1) is essential regulator of apoptosis and inactivation by DNA methylation is common event in numerous cancer types. We investigated the regulation of APAF-1 through DNA methylation in pancreatic cancer. MATERIALS AND METHODS: Datasets from 44 patients after pancreatoduodenectomy and the pancreatic adenocarcinoma (PDAC) cell lines Capan-2 and MIA PaCa-2 treated with decitabine were analyzed by RT-PCR, immunoblotting, methylation-specific PCR analysis, apoptosis and viability assays to identify effects of APAF-1 regulation. RESULTS: APAF-1 mRNA and protein levels were significantly down-regulated, and APAF-1 methylation status was associated with perineural invasion in PDAC. Decitabine inhibited cell viability and increased apoptosis rates, however failed to restore APAF-1 mRNA and protein levels in cells. CONCLUSION: APAF-1 gene hypermethylation may contribute to the progression of PDAC through perineural invasion. Decitabine could sensitize pancreatic cancer cells to apoptosis and growth retardation, however, not directly through the APAF-1 demethylation process.

Preoperative Platelet to Lymphocyte Ratio as a Prognostic Factor for Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Various inflammatory markers have been investigated for a prognostic role in patients with resectable pancreatic cancer. However, the value of preoperative platelet to lymphocyte ratio (PLR) remains controversial. We performed a systematic review and meta-analysis of PLR as a preoperative prognostic factor for resectable pancreatic cancer. MATERIAL AND METHODS: Systematic literature search was conducted for studies assessing PLR influence as a preoperative prognostic factor in resectable pancreatic cancer patients. Random-effects model was applied for pooling hazard ratios and 95% confidence intervals related to overall survival (OS) and disease-free survival (DFS). RESULTS: Fourteen articles with 2,743 patients were included in the study. According to the analysis, high PLR had no correlation with decreased OS. Due to high heterogeneity among studies, subgroup analysis was performed. Better OS was associated with low PLR in Asian patients, patients with mixed type of operation performed, and patients with preoperative PLR ≤150. Low PLR was associated with significantly better DFS. CONCLUSIONS: PLR is a predictive factor of better DFS in patients with resectable pancreatic cancer. However, available evidence does not support PLR as a reliable prognostic factor for OS.

Long-Term Impact of Iatrogenic Bile Duct Injury.

BACKGROUND: Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis. METHODS: We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. RESULTS: Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10-20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. CONCLUSIONS: The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.

CT- and MRI-Based Assessment of Body Composition and Pancreatic Fibrosis Reveals High Incidence of Clinically Significant Metabolic Changes That Affect the Quality of Life and Treatment Outcomes of Patients with Chronic Pancreatitis and Pancreatic Cancer.

Background and Objectives: Both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) may lead to cachexia, sarcopenia, and osteoporosis due to different mechanisms. Neither patient gender, age, nor body weight are good predictors of these metabolic changes having a significant negative impact on the quality of life (QOL) and treatment outcomes. The aim of this study was to evaluate radiological changes in body composition and to compare them with manifestations of exocrine and endocrine pancreatic insufficiency, body mass, and QOL among patients with CP and PDAC. Materials and Methods: Prospectively collected data of 100 patients with diagnosed CP or PDAC were used for analysis. All patients underwent dual-energy X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) was used to assess QOL. Diabetes and changes in fecal elastase-1 were also assessed. Results: There was no significant difference in skeletal muscle mass (SMM) among patients with CP and PDAC (p = 0.85). Significantly more underweight patients had low SMM (p = 0.002). Patients with CP had more pronounced pancreatic fibrosis (PF) (p < 0.001). Data showed a significant relationship between a high degree of PF and occurrence of diabetes (p = 0.006) and low fecal elastase-1 levels (p = 0.013). A statistically significant lower QOL was determined in patients with PF ≥ 50% and in the CP group. Conclusions: Sarcopenia and osteoporosis/osteopenia are highly prevalent among patients with chronic pancreatitis and pancreatic cancer, and CT- and MRI-based assessment of body composition and pancreatic fibrosis could be a potentially useful tool for routine detection of these significant metabolic changes.

Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells.

AIM: To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells. METHODS: AGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin. RESULTS: AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively. CONCLUSION: In addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.

Long-term Survival of Patient with Ampulla of Vater Metastasis of Renal Cell Carcinoma.

Ampulla of Vater metastases from renal cell carcinoma are rare. The time between detection of the primary tumour and its metastasis may extend to years. Management should be aggressive, since the prognosis of renal cell carcinoma is unpredictable and curative surgery of metastases may extend patient survival and even lead to definite cure. Herein we report a case of long-term survival after successful surgical treatment of a renal cell carcinoma metastasis to the ampulla of Vater. A 62-year-old man with a history of renal cell carcinoma in the left kidney underwent a successful left nephrectomy. Eight months later duodenoscopy showed a tumour at the site of papilla of Vater. Biopsy confirmed the diagnosis of carcinoma. Contrast enhanced computer tomography scan verified the periampullary mass, dilatation of the pancreatic and the common bile duct. No radiological signs of either local advancement or distant metastases were present. Pylorus-preserving pancreatoduodenectomy with lymphadenectomy was performed. Pathology report disclosed metastatic lesions in the papilla of Vater from the clear cell carcinoma of the kidney. The postoperative course was uneventful, and the patient lived for 14 years after pancreatoduodenectomy and, following thorough investigations, was free from local and systemic recurrence. Pancreatoduodenectomy can provide long-term survival in selected cases with solitary papilla of Vater metastasis from renal cell carcinoma. Favourable long-term survival rates suggest that these patients should be considered candidates for pancreatoduodenectomy if experienced pancreatic surgeon is available and no other metastases are found.

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery in the elderly.

: The risk for postoperative venous thromboembolism (VTE) is increased in patients aged more than 70 years and in elderly patients presenting with co-morbidities, for example cardiovascular disorders, malignancy or renal insufficiency. Therefore, risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis are essential in this patient population. Timing and dosing of pharmacoprophylaxis may be adopted from the non-aged population. Direct oral anti-coagulants are effective and well tolerated in the elderly; statins may not replace pharmacological thromboprophylaxis. Early mobilisation and use of non-pharmacological means of thromboprophylaxis should be exploited. In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C). We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C). We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C). In elderly patients with renal failure, low-dose unfractionated heparin (UFH) may be used or weight-adjusted dosing of low molecular weight heparin (Grade 2C). In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C). We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, low molecular weight heparin (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C). : This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to:Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73-76.A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Executive summary. Eur J Anaesthesiol 2018; 35:77-83.

How severe is moderately severe acute pancreatitis? Clinical validation of revised 2012 Atlanta Classification.

AIM: To explore the outcomes and the appropriate treatment for patients with moderately severe acute pancreatitis (AP). METHODS: Statistical analysis was performed on data from the prospectively collected database of 103 AP patients admitted to the Department of Surgery, Hospital of Lithuanian University of Health Sciences in 2008-2013. All patients were confirmed to have the diagnosis of AP during the first 24 h following admission. The severity of pancreatitis was assessed by MODS and APACHE II scale. Clinical course was re-evaluated after 24, 48 and 72 h. All patients were categorized into 3 groups based on Atlanta 2012 classification: Mild, moderately severe, and severe. Outcomes and management in moderately severe group were also compared to mild and severe cases according to Atlanta 1992 and 2012 classification. RESULTS: Fifty-three-point four percent of patients had edematous while 46.6 % were diagnosed with necrotic AP. The most common cause of AP was alcohol (42.7%) followed by alimentary (26.2%), biliary (26.2%) and idiopathic (4.9%). Under Atlanta 1992 classification 56 (54.4%) cases were classified as "mild" and 47 (45.6%) as "severe". Using the revised classification (Atlanta 2012), the patient stratification was different: 49 (47.6%) mild, 27 (26.2%) moderately severe and 27 (26.2%) severe AP cases. The two severe groups (Atlanta 1992 and Revised Atlanta 2012) did not show statistically significant differences in clinical parameters, including ICU stay, need for interventional treatment, infected pancreatic necrosis or mortality rates. The moderately severe group of 27 patients (according to Atlanta 2012) had significantly better outcomes when compared to those 47 patients classified as severe form of AP (according to Atlanta 1992) with lower incidence of necrosis and sepsis, lower APACHE II (P = 0.002) and MODS (P = 0.001) scores, shorter ICU stay, decreased need for interventional and surgical treatment. CONCLUSION: Study shows that Atlanta 2012 criteria are more accurate, reduce unnecessary treatments for patients with mild and moderate severe pancreatitis, potentially resulting in health costs savings.

Response of OVCAR-3 Cells to Cisplatin and Hyperthermia: Does Hyperthermia Really Matter?

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is proposed as a promising treatment method, but fundamental information about the contribution of hyperthermia to intraperitoneal chemotherapy is lacking. The purpose of this study was to investigate the cytotoxic effect of hyperthermia and cisplatin on OVCAR-3 cells in vitro. MATERIALS AND METHODS: Imitating the typical clinical conditions of HIPEC, OVCAR-3 cells were exposed to hyperthermia and cisplatin for 1 h. MTT viability test, flow cytometric analysis, and real-time cell and isobologram analysis were performed. RESULTS: Hyperthermia up to 42°C did not significantly increase the effect of cisplatin regarding the viability and apoptosis of OVCAR-3 cells. Moreover, an antagonistic effect of hyperthermia and cisplatin was revealed. CONCLUSION: Our investigation of OVCAR-3 cells critically disputes the benefit of hyperthermia in ovarian cancer treatment. Further in vitro and in vivo research is essential for better understanding of the mechanisms of action of hyperthermia and its role in the treatment of epithelial ovarian cancer.

Preoperative Endoscopic Biliary Drainage May Negatively Impact Survival Following Pancreatoduodenectomy for Ampullary Cancer.

BACKGROUND/AIMS: Ampullary carcinoma is a rare tumour with a high resectability rate. There is an increasing body of evidence indicating not only tumour-related factors, but also jaundice influence survival following curative resection. Several modalities for preoperative biliary drainage are available; however, routine preoperative endoscopic biliary drainage (PEBD) is not recommended. There is no sufficient data regarding the impact of PEBD on long-term outcomes. The aim of our study was to identify predictive factors of survival with special regard to PEBD in patients undergoing curative resection for ampullary carcinoma. PATIENTS AND METHODS: Data from 64 consecutive patients with adenocarcinoma of the papilla of Vater who have been operated on was analysed. Overall survival was defined from the date of surgery to the date of death, or censored at the last patient contact. Survival analysis was determined by means of the Kaplan-Meier method. The significance of the demographic, clinical and histopathologic factors was ascertained by the log-rank test. A Cox proportional hazard model was used to determine independent prognostic factors of survival. RESULTS: Twenty patients (31.2%) underwent PEBD. Univariate analysis revealed tumour-related factors, age over 70, and PEBD to negatively influence survival. Five of them (excluding T stage) were identified as the independent prognosticators, while PEBD appeared to be the most decisive factor. Median survival for patients who underwent PEBD was 25.3 months as compared to 112.9 months for those who did not. In conclusion, PEBD negatively affected long-term outcomes in our patients with resected ampullary carcinoma.

Factors influencing survival after pancreatoduodenectomy for ductal adenocarcinoma depend on patients' age.

BACKGROUND: It is supposed that a prolonged lifetime will be associated with increased incidence of PDAC among the elderly. Some studies show a tendency toward decreased survival in the elderly patients following pancreatoduodenectomy for PDAC. The aim of this study was to evaluate factors, influencing survival following pancreatoduodenectomy for PDAC in different age groups. METHODS: Data of 251 patients after pancreatoduodenectomy for PDAC between 1999 and 2012 were analyzed. The Kaplan-Meier method and log-rank test were used to calculate survival and to compare differences between groups. The Cox proportional hazard model was applied to indentify independent prognosticators. RESULTS: The overall median survival was 14.9 months. Postoperative morbidity was 25.5% with a 5.1% mortality rate. No significant differences in the overall morbidity (22.4 vs. 29.6%) or mortality (2.8 vs. 8.3%) rates were observed between different patients' age groups (<70 years and >70 years). Multivariate analysis revealed R1 resection (HR 1.76) and poor tumor differentiation (G3-G4) (HR 1.48) were independent negative factors for survival in patients <70 years. Lymph-node metastases (N1) - HR 4.89 and perineural invasion - HR 2.73 were independent prognosticators in the elderly. CONCLUSIONS: Our study highlighted different factors influencing long-term survival after pancreatoduodenectomy: R1 resection and poor tumor differentiation (G3-G4) were independent negative factors for survival in patients <70 years, while perineural invasion and lymph-node metastases result in worse survival among the elderly.