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.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

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.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

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.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

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.

Multiple risk factors for diabetes mellitus in patients with chronic pancreatitis: A multicentre study of 1117 cases.

BACKGROUND: Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis. METHODS: We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes. RESULTS: The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all p ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all p ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes (p = 0.07). CONCLUSION: In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.

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.

Magnetic Resonance Imaging as a Valid Noninvasive Tool for the Assessment of Pancreatic Fibrosis.

OBJECTIVES: The aim of this study was to evaluate the utility of magnetic resonance imaging (MRI) for the noninvasive assessment of pancreatic fibrosis (PF). METHODS: Fifty-two patients who underwent surgical resection of the pancreas, histological examination of resection margins, preoperative abdominal MRI, and fecal elastase-1 test were enrolled in the study. Pancreatic tissue was identified on the MRI T1-, T2-, and diffusion-weighted imaging sequences. Apparent diffusion coefficient (ADC) was measured at the expected resection margin of the pancreas. RESULTS: There was a significant negative correlation between the ADC mean and histologically determined PF (r = -0.752, P = 0.001). For equal to or greater than 25% of PF, the ADC cutoff value was 1.331 or less, with a sensitivity of 77% and specificity of 88%. The unenhanced T1-weighted signal intensity ratio (T1SI) cutoff value was 172.1 or less. For equal to or greater than 50% of PF, the ADC cutoff value was 1.316 or less with a sensitivity of 85% and specificity of 88%. The highest sensitivity was obtained by combining ADC and T1SI values. CONCLUSIONS: Combining both the ADC and T1SI measurement allows the detection of early PF with good sensitivity and specificity. Magnetic resonance imaging has the advantage of being noninvasive and widely used in the clinical setting, thus making our results easily transferable to routine clinical practice.

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.