68Ga-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the 68Ga-FAPI PET Observational Trial.

The fibroblast activation protein (FAP) is highly expressed on carcinoma-associated fibroblasts in the stroma of pancreatic cancer and thus is a promising target for imaging and therapy. Preliminary data on PET imaging with radiolabeled FAP inhibitors (FAPIs) demonstrate superior tumor detection. Here we assess the accuracy of FAP-directed PET in patients with pancreatic cancer. Methods: Of 64 patients with suspected or proven pancreatic cancer, 62 (97%) were included in the data analysis of the 68Ga-FAPI PET observational trial (NCT04571086). All of these patients underwent contrast-enhanced CT, and 38 patients additionally underwent 18F-FDG PET. The primary study endpoint was the association of 68Ga-FAPI PET uptake intensity and histopathologic FAP expression. Secondary endpoints were detection rate, diagnostic performance, interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met: The association between 68Ga-FAPI SUVmax and histopathologic FAP expression was significant (Spearman r, 0.48; P = 0.04). For histopathology-validated lesions, 68Ga-FAPI PET showed high sensitivity and positive predictive values (PPVs) on per-patient (sensitivity, 100%; PPV, 96.3%) and per-region (sensitivity, 100%; PPV, 97.0%) bases. In a head-to-head comparison versus 18F-FDG or contrast-enhanced CT, 68Ga-FAPI detected more tumor on a per-lesion (84.7% vs. 46.5% vs. 52.9%), per-patient (97.4% vs. 73.7% vs. 92.1%), or per-region (32.6% vs. 18.8% vs. 23.7%) basis, respectively. 68Ga-FAPI PET readers showed substantial overall agreement on the basis of the Fleiss κ: primary κ, 0.77 (range, 0.66-0.88). Minor and major changes in clinical management occurred in 5 patients (8.4%) after 68Ga-FAPI PET. Conclusion: We confirmed an association of 68Ga-FAPI PET SUVmax and histopathologic FAP expression in pancreatic cancer patients. Additionally, we found high detection rate and diagnostic accuracy, superior to those of 18F-FDG PET/CT. 68Ga-FAPI might become a powerful diagnostic tool for pancreatic cancer work-up.

Quality of Care Transition During Hospital Discharge, Patient Safety, and Weight Regain After Bariatric Surgery: a Cross-Sectional Study.

PURPOSE: Bariatric surgery is established as the gold standard in the treatment of severe obesity. However, a significant proportion of patients experience a substantial weight regain afterwards. Previous research focused predominantly on patients' personal factors. Yet, critical discharge process factors that contribute to patient's adherence after surgical interventions are rarely examined. This study investigated whether high quality of care transitions in discharge management influences weight regain and the likelihood of experiencing adverse patient safety incidents. MATERIALS AND METHODS: A cross-sectional study with 578 patients after bariatric surgery was conducted. Participants answered a standardized assessment on the quality of care transition from hospital to home-, surgery-, and nutrition-related characteristics as well as patient safety incidents. RESULTS: Significant weight regain was observed 24 months after surgery. The association between time since surgery and weight regain was weaker in patients with high quality of care transitions (B = 2.27, p < .001). Higher quality of care transition was also significantly related to a lower likelihood of unplanned hospital readmissions (OR = 0.67) and fewer medication complications (OR = 0.48) after surgery. CONCLUSION: This study sheds first light on the key influence of high quality of care transitions after bariatric surgery. Improvement efforts into effective discharge processes may establish smoother care transitions and help patients to assume responsibility and compliance with behavioral recommendations after surgery. Moreover, adverse patient safety incidents are less frequent after high quality care transitions indicating both high quality of health services for patients and reducing costs for the health care system.

Needs and Demands for e-Mental Health Interventions in Individuals with Overweight and Obesity: User-Centred Design Approach.

INTRODUCTION: Several studies indicate an association between mental disorders and overweight or obesity. E-Mental health interventions offer an effective way to overcome barriers to health care access for individuals with overweight and obesity. The objective of this study was to examine the needs and demands for e-mental health interventions among individuals with overweight and obesity. METHODS: A cross-sectional study was conducted from 2020 to 2021 in Germany. A total of 643 participants were recruited through specialized social media platforms and the Alfried-Krupp hospital in Essen, Germany. Sociodemographic and medical data were analysed, as well as data on depressive symptoms and on the needs and demands for e-mental health interventions. RESULTS: Contact with and recommendation by experts appear to be key aspects in the acceptance and use of e-mental health interventions. In summary, most participants preferred a 20-30-min weekly session via smartphone over a 4-month period. The highest preference in terms of features included practicing coping skills and being provided with information; in regard to desired topics, nutrition consultation, quality of life, and adapting to new life situations were considered most important. DISCUSSION: e-Mental health interventions can be highly beneficial for individuals, especially when developed through a user-centred design approach. The results of the study indicate which content and design are preferred and, thereby, provide valuable information for consideration when developing a tailored e-mental health intervention.

Fibroblast-Activation Protein PET and Histopathology in a Single-Center Database of 324 Patients and 21 Tumor Entities.

We present an overview of our prospective fibroblast-activation protein inhibitor (FAPI) registry study across a 3-y period, with head-to-head comparison of tumor uptake in 68Ga-FAPI and 18F-FDG PET, as well as FAP immunohistochemistry. Methods: This is an interim analysis of the ongoing 68Ga-FAPI PET prospective observational trial at our department. Patients who underwent clinical imaging with 68Ga-FAPI PET between October 2018 and October 2021 were included. Tracer uptake was quantified by SUVmax for tumor lesions and by SUVmean for normal organs. PET tumor volume (40% isocontour) and tumor-to-background ratios were calculated. Correlation between SUVmax and FAP staining in tissue samples was analyzed. Results: In total, 324 patients with 21 different tumor entities underwent 68Ga-FAPI imaging; 237 patients additionally received 18F-FDG PET. The most common tumor entities were sarcoma (131/324, 40%), pancreatic cancer (67/324, 21%), and primary tumors of the brain (22/324, 7%). The mean primary tumor SUVmax was significantly higher for 68Ga-FAPI than 18F-FDG among pancreatic cancer (13.2 vs. 6.1, P < 0.001) and sarcoma (14.3 vs. 9.4, P < 0.001), and the same was true for mean SUVmax in metastatic lesions of pancreatic cancer (9.4 vs. 5.5, P < 0.001). Mean primary tumor maximum tumor-to-background ratio was significantly higher for 68Ga-FAPI than 18F-FDG across several tumor entities, most prominently pancreatic cancer (14.7 vs. 3.0, P < 0.001) and sarcoma (17.3 vs. 4.7, P < 0.001). Compared with 18F-FDG, 68Ga-FAPI showed superior detection for locoregional disease in sarcoma (52 vs. 48 total regions detected) and for distant metastatic disease in both sarcoma (137 vs. 131) and pancreatic cancer (65 vs. 57), respectively. Among 61 histopathology samples, there was a positive correlation between 68Ga-FAPI SUVmax and overall FAP immunohistochemistry score (r = 0.352, P = 0.005). Conclusion: 68Ga-FAPI demonstrates higher absolute uptake in pancreatic cancer and sarcoma, as well as higher tumor-to-background uptake along with improved tumor detection for pancreatic cancer, sarcoma, and other tumor entities when compared with 18F-FDG. 68Ga-FAPI is a new tool for tumor staging with theranostic potential.

Development and Validation of Dietary Behavior Inventory-Surgery (DBI-S) in the Scope of International Post-Bariatric Surgery Guidelines and Recommendations.

(1) Dietary behavior is highly relevant for patients after bariatric surgery. No instrument exists assessing adherence to medical guidelines concerning the dietary behavior of patients after bariatric surgery. The aim of this study was to develop and validate such an instrument. (2) Data from patients after bariatric surgery (n = 543) were collected from March to May 2022. The development of the DBI-S was theory-based and interdisciplinary. Items' and content validity of the DBI-S were examined. (3) The final version of the DBI-S consists of 13 items. Convergent validation was confirmed by significant correlations between DBI-S score and attitude towards healthy food (r = 0.26, p = <0.001) and impulsivity (r = −0.26, p = <0.001). Criterion validity was confirmed by significant correlations between DBI-S score and pre-/post-surgery BMI difference (r = −0.14, p = 0.002), pre-/post-surgery weight difference (r = 0.13, p = 0.003), and quality of life (r = 0.19, p = <0.001). Cluster analysis confirmed the ability to distinguish between two dietary behavior clusters (rather healthy and rather unhealthy). (4) The DBI-S is an economic and valid instrument to assess the adherence of post-bariatric surgery patients to the relevant dietary behavior recommendations and guidelines and can distinguish between rather unhealthy and healthy dietary behavior.

Determinants of Acceptance of Weight Management Applications in Overweight and Obese Individuals: Using an Extended Unified Theory of Acceptance and Use of Technology Model.

Overweight and obesity carry a tremendous burden in terms of physiological and psychological comorbidities. There is a great variety of weight management applications to support weight reduction, but a systematical analysis of individuals' needs and requirements to adopt sustaining lifestyle changes is missing so far. This study aimed to assess the acceptance of such applications and its underlying predictors in individuals with overweight/obesity. A cross-sectional study was conducted, including 439 overweight/obese individuals. Health-related internet use and acceptance of weight management applications were examined using a modified questionnaire based on the Unified Theory of Acceptance and Use of Technology (UTAUT). The general acceptance of weight management applications was high, with significant age differences. Compared to older individuals, younger ones showed a higher acceptance. BMI was not significantly associated with acceptance. Besides psychometric data and eHealth-related data, performance expectancy, effort expectancy, and social influence proved to be significant predictors for acceptance. The total variance explanation provided by the extended UTAUT model was 61.2%. The knowledge of the influencing factors on acceptance might be useful in developing, optimizing, and establishing weight management applications. For determining acceptance and its predictors of weight management applications, the UTAUT model is a valid approach.

Predicting Acceptance of e-Mental Health Interventions in Patients With Obesity by Using an Extended Unified Theory of Acceptance Model: Cross-sectional Study.

BACKGROUND: The rapid increase in the number of people who are overweight and obese is a worldwide health problem. Obesity is often associated with physiological and mental health burdens. Owing to several barriers to face-to-face psychotherapy, a promising approach is to exploit recent developments and implement innovative e-mental health interventions that offer various benefits to patients with obesity and to the health care system. OBJECTIVE: This study aims to assess the acceptance of e-mental health interventions in patients with obesity and explore its influencing predictors. In addition, the well-established Unified Theory of Acceptance and Use of Technology (UTAUT) model is compared with an extended UTAUT model in terms of variance explanation of acceptance. METHODS: A cross-sectional web-based survey study was conducted from July 2020 to January 2021 in Germany. Eligibility requirements were adult age (≥18 years), internet access, good command of the German language, and BMI >30 kg/m2 (obesity). A total of 448 patients with obesity (grades I, II, and III) were recruited via specialized social media platforms. The impact of various sociodemographic, medical, and mental health characteristics was assessed. eHealth-related data and acceptance of e-mental health interventions were examined using a modified questionnaire based on the UTAUT. RESULTS: Overall, the acceptance of e-mental health interventions in patients with obesity was moderate (mean 3.18, SD 1.11). Significant differences in the acceptance of e-mental health interventions among patients with obesity exist, depending on the grade of obesity, age, sex, occupational status, and mental health status. In an extended UTAUT regression model, acceptance was significantly predicted by the depression score (Patient Health Questionnaire-8; ß=.07; P=.03), stress owing to constant availability via mobile phone or email (ß=.06; P=.02), and confidence in using digital media (ß=-0.058; P=.04) and by the UTAUT core predictors performance expectancy (ß=.45; P<.001), effort expectancy (ß=.22; P<.001), and social influence (ß=.27; P<.001). The comparison between an extended UTAUT model (16 predictors) and the restrictive UTAUT model (performance expectancy, effort expectancy, and social influence) revealed a significant difference in explained variance (F13,431=2.366; P=.005). CONCLUSIONS: The UTAUT model has proven to be a valuable instrument to predict the acceptance of e-mental health interventions in patients with obesity. The extended UTAUT model explained a significantly high percentage of variance in acceptance (in total 73.6%). On the basis of the strong association between acceptance and future use, new interventions should focus on these UTAUT predictors to promote the establishment of effective e-mental health interventions for patients with obesity who experience mental health burdens.

Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD.

The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression.Abbreviations: ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson's correlation coefficient (r); rs: Spearman's rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue.

Generalized Anxiety as a Risk Factor for Dysfunctional Eating Behavior after Obesity Surgery during the COVID-19 Pandemic.

Purpose: The present study investigates the impact of obesity surgery on mental health (i.e., eating behavior and distress) during the COVID-19 pandemic. Methods: Two hundred fifty-four participants were recruited via social media. One hundred fourteen (44.53%) of them were surgery candidates (waiting for obesity surgery), while 142 (55.46%) had already undergone surgery. Participants who underwent surgery were compared to participants that did not yet undergo surgery in terms of mental burden (depression and anxiety), as well as safety and eating behavior. Further moderation analyses attempted to identify risk factors for increased COVID-19-related dysfunctional eating behavior after surgery. Results: Participants who underwent surgery showed generally lower levels of depression and general anxiety on a trend level. Moderation analyses suggested that people with high levels of generalized anxiety actually show more dysfunctional COVID-19-specific eating behavior after obesity surgery. Conclusion: On a trend level, obesity surgery appears to attenuate symptoms of generalized anxiety and depression. Yet, surgery patients with high levels of generalized anxiety exhibit even higher levels of dysfunctional eating during the COVID-19 pandemic. It is therefore particularly important to support people at risk.

Postoperative results, pathologic outcome, and long-term patency rate of autologous vein reconstruction of the mesentericoportal axis after pancreatectomy.

PURPOSE: In advanced pancreatic cancer (PC), en-bloc vein resection and reconstruction (VR) is a curative option in oncologic pancreatectomy. However, few data about long-term patency rates after autologous venous reconstruction are available. We aimed to analyze whether early postoperative morbidity is increased by additional VR. Furthermore, pathologic outcomes and long-term patency rates after applying autologous vein material are examined. METHODS: Data on patients who underwent surgical resection for suspicious malignancy were collected prospectively. Early postoperative complications, as well as the circumferential resection margins were analyzed retrospectively. Patients with VR (VR+) were compared with patients without vein resection (VR-). Vein reconstruction was always performed by autologous vein replacement, followed by a 6-month application of Enoxaparin. Patency rates of the mesenteric vessels in long-term follow-up exams were determined by contrast-enhanced computed tomography (CT) every 3 months. RESULTS: Two hundred nineteen pancreatic resections for suspicious malignancy were performed. In 82 patients, VR occurred (37.4%). No significant differences between VR+ and VR- were observed concerning 30-day mortality and postoperative morbidity. R0 rate did not differ between the two groups. By applying autologous vein material, the average patency rate was 90%. CONCLUSION: In terms of tumor free resection margins, equal oncologic results can be achieved by additional vein resection. Because the patency rate is high in follow-up, and early postoperative complication rates are not increased in patients with VR+, vein resection and reconstruction should be performed if oncologically necessary. The application of autologous vein reconstruction followed by a 6-month enoxaparin treatment seems to yield favorable technical results.

Identification of Patients with Pancreatic Cancer by Electron Paramagnetic Resonance Spectroscopy of Fatty Acid Binding to Human Serum Albumin.

An effective biological marker for pancreatic adenocarcinoma (PAC) is not available so far. Here, we investigate how electron paramagnetic resonance (EPR) spectroscopy of spin-labeled fatty acid (FA) molecules binding to human serum albumin (HSA) in human serum is a suitable method for the identification of patients with PAC through detection of PAC-induced changes of FA binding to albumin. The functionality of HSA to bind FA is investigated in serum samples of 35 patients with PAC, 26 patients with benign pancreatic tumors (BPD), and 24 healthy individuals by continuous wave (CW) EPR spectroscopy by simply dissolving 16-DOXYL stearic acid as spin-labeled FA. It is found that FA binding to HSA in PAC is significantly modified when compared with healthy and BPD individuals. The PAC group could best be discriminated from the healthy group based on EPR characteristics at the loading ratio of 1:4 (HSA:FA), while patients with PAC and BPD are distinguishable at a loading ratio of 1:6. Using nanoscale distance measurements through double electron-electron resonance (DEER), it is found that the distribution of FAs in the HSA of one PAC patient is similar to that of FAs in healthy individuals. Combining all EPR spectroscopic data, this leads to a tentative molecular interpretation of only small changes in hydration at the protein's surface as origin of the detectable characteristics for PAC patients. Thus, EPR of FA/HSA binding is a simple and promising tool for clinical detection of patients with PAC and needs to be tested with larger ensembles of different patient groups.

The Impact of Psychological Resources on Body Mass Index in Obesity Surgery Candidates.

BACKGROUND: Obesity surgery is the therapy of choice for severely obese patients. The results are promising, but at the same time obesity surgery represents a physical and psychological challenge for patients and care givers. In order to give psychosocial support adequately, more knowledge of effects of psychological profiles is required. Research is often deficit and symptom oriented. Psychological resources (competences) of individuals are often neglected. However, after surgery patients have to cope with the altered anatomic condition and therefore psychological resources are essential for a successful development and my influence also the surgical outcome. The interplay of eating behavior, depression, and psychological resources and their influence on weight are yet undetermined. METHODS: A cross-sectional study in consecutive obesity surgery candidates was performed. One hundred twenty-seven participants were included (90 female, 37 male; mean BMI 49.85 kg/m²; range 36.7-84.2 kg/m²). After conducting semi-structured clinical interviews psychological resources, depression and eating behavior were assessed via three questionnaires: Essener Ressourcen-Inventar (ERI), Patient Health Questionnaire depression module (PHQ-d), and Eating Disorder Examination-Questionnaire (EDE-Q). To evaluate the influence of psychological resources on BMI mediation models and path analyses were performed. RESULTS: Psychological resources do not influence BMI directly. Path analyses revealed depression as well as depression/eating behavior as mediating dimension. A first path showed that higher psychological resources are associated with less depressive symptoms and lower BMI. On the other side, a second path showed that higher psychological resources are related to less depression and by means of more conscious and controlled eating behavior to a lower BMI. CONCLUSION: Psychological resources seem to be relevant in the context of obesity surgery. Good psychological resources show plausible associations with less depression and a more adequate eating behavior. The evaluation of psychological resources in obesity surgery candidates allows the identification of patients at risk. Competences of patients should be addressed in the context of surgery. Our findings build a foundation for a more individualized supportive treatment for obesity surgery candidates. Improving impaired psychological resources may help in the coping process after surgery and is supposed to lead to an even higher weight loss.

Influence of Clinical pathways on treatment and outcome quality for patients undergoing pancreatoduodenectomy? A retrospective cohort study.

BACKGROUND: Pancreatic surgery demands complex multidisciplinary management. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated the effect of CPs on quality of care for pancreatoduodenectomy. METHODS: Data of all consecutive patients who underwent pancreatoduodenectomy before (n = 147) or after (n = 148) CP introduction were evaluated regarding catheter and drain management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates. RESULTS: Catheters and abdominal drainages were removed significantly earlier in patients treated with CP (p < 0.0001). First intake of liquids, nutritional supplement and solids was significantly earlier in the CP group (p < 0.0001). Exocrine insufficiency was significantly less common after CP implementation (47.3% vs. 69.7%, p < 0.0001). The number of patients receiving intraoperative transfusion dropped significantly after CP implementation (p = 0.0005) and transfusion rate was more frequent in the pre-CP group (p = 0.05). The median number of days with maximum pain level >3 was significantly higher in the CP group (p < 0.0001). There was no significant difference in mortality, morbidity, reoperation and readmission rates. CONCLUSIONS: Following implementation of a CP for pancreatoduodenectomy, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.

Clinical Pathways For Pancreatic Surgery: Are They A Suitable Instrument For Process Standardization To Improve Process And Outcome Quality Of Patients Undergoing Distal And Total Pancreatectomy? - A Retrospective Cohort Study.

PURPOSE: Pancreatic surgery demands complex multidisciplinary management, which is often cumbersome to implement. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated if CPs are a suitable tool for process standardization in order to improve process and outcome quality in patients undergoing distal and total pancreatectomy. PATIENTS AND METHODS: Data of consecutive patients who underwent distal or total pancreatectomy before (n=67) or after (n=61) CP introduction were evaluated regarding catheter management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates. RESULTS: The usage of incentive spirometers for pneumonia prophylaxis increased. The median number of days with hyperglycemia decreased significantly from 2.5 to 0. For distal pancreatectomy, the incidence of postoperative diabetes dropped from 27.9% to 7.1% (p=0.012). The incidence of postoperative exocrine pancreatic insufficiency decreased from 37.2% to 11.9% (p=0.007). There was no significant difference in mortality, morbidity, reoperation and readmission rates between groups. CONCLUSION: Following implementation of a pancreatic surgery CP, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.

Redo Surgery After Duodenum-Preserving Pancreatic Head Resection for Chronic Pancreatitis: High Incidence in Long-Term Follow-up.

INTRODUCTION: Duodenum-preserving pancreatic head resection is a safe procedure with a more favorable short-term outcome compared to pancreaticoduodenectomy. However, some patients develop mechanical complications or suspicion of malignancy during follow-up and need reoperation years after primary surgery. Aim of this study was to evaluate incidence, techniques, and complication rates of redo operations. MATERIALS AND METHODS: We reviewed short- and long-term outcomes of 33 patients who underwent duodenum-preserving pancreatic head resection for chronic pancreatitis from 1997 to 2010 at our department from a prospective database. RESULTS: Short-term outcome after duodenum-preserving pancreatic head resection was comparable with previous data. Follow-up (mean 89 months) was achieved for 26 patients. Eight patients (30.1 %) needed a redo operation of which seven were performed. Indications were obstructive jaundice (four patients) and suspicion of cancer of pancreatic head (four patients; carcinoma confirmed in three patients). Mean interval between initial and redo operation was seven years for benign stenoses and 4 years for cancer. Three of seven operated patients needed revision. CONCLUSION: Need for redo operations after duodenum-preserving pancreatic head resection is high and these operations have high complication rates. In most cases, redo operations can be avoided by performing pancreaticoduodenectomy as initial operation.

Evaluation of POSSUM for patients undergoing pancreatoduodenectomy.

BACKGROUND: The POSSUM score is a predictive scoring system for postoperative morbidity. Although numerous studies have validated its application in major abdominal surgery, few have exclusively considered pancreatic resections, which have unique complications that are costly and problematic. We examined whether POSSUM could accurately reflect the clinical outcomes in pancreatic resection. METHODS: A total of 694 consecutive resections of the pancreatic head were performed between 1993 and 2010 at the Department of General, Thoracic, and Vascular Surgery at the University Hospital Dresden. The POSSUM score calculated for each case was compared with the observed morbidity. Relevance and predictive performance of the score were assessed; in particular, because of the poor calibration of the POSSUM predictions on the Dresden data, a new score was created that was externally validated on patient cohorts from two different centers for pancreatic surgery. RESULTS: The goodness-of-fit analysis revealed that the POSSUM score was not well calibrated because the POSSUM-predicted morbidity rate was 58.9% on average whereas the observed morbidity rate was 43.4%. Discrepancies occurred particularly among the predicted high-risk patients, for whom the score actually overestimated the morbidity risk. Therefore, we adapted the score and complemented it with additional prognostic parameters. The new score was validated in a patient cohort from two other German centers and fitted better to the data. CONCLUSION: The new score, named PS-POSSUM (POSSUM in pancreatic surgery), fits the data better. However, the prediction ability remains rather poor. PS-POSSUM may still be helpful, as it draws attention to additional risk and protective factors in addition to those in the original POSSUM score.

Case report: Intraductal tubulopapillary neoplasm of the pancreas with unique clear cell phenotype.

Intraductal tubulopapillary neoplasms of the pancreas are very rare tumors characterized by intraductal tubulopapillary growth, ductal differentiation, scant intracellular mucin production and cellular dysplasia. Here, we report the first case of an intraductal tubulopapillary neoplasm of the pancreas with clear cell morphology. The tumor was detected during the diagnostic work-up of acute pancreatitis in a 43- year old female. Histological examination revealed a tumor with the typical architecture of an intraductal tubulopapillary neoplasm of the pancreas with tumor cells showing abundant clear cytoplasm and Di-PAS negativity. Immunohistochemistry revealed positivity for Pan-CK, CK7, CK8/18, MUC1, MUC6, carbonic anhydrase IX, CD10, EMA, ß-catenin and e-cadherin. Sanger sequencing did not detect mutations for ß-catenin, BRAF, KRAS, PIK3CA and GNAS. Altogether, histology, immunohistochemical expression profile (MUC1+, MUC6+, MUC2-, MUC5AC-, thrypsin-, chymotrypsin-, CDX2-) and sequencing results led to the diagnosis of intraductal tubulopapillary neoplasm. However, the neoplasm consisted of cells showing abundant clear cytoplasm, a morphological pattern not being described so far in the current classification of pancreatic intraductal neoplasms. Potential differential diagnosis and the molecular basis of clear cell morphology are discussed. In conclusion, we consider this tumor as intraductal tubulopapillary neoplasm of the pancreas with unique clear cell phenotype. After surgery and without adjuvant therapy, the patient's clinical course has been uneventful for over two years now. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1051828790117127.

Factors predicting long-term survival following pancreatic resection for ductal adenocarcinoma of the pancreas: 40 years of experience.

BACKGROUND: Long-term survival after resection for pancreas carcinoma has rarely been reported. Factors influencing long-term survival are still under debate. The aim of this study was to define predictors for long-term survival. METHODS: Between 1972 and 2004, a total of 415 patients underwent resection. Data were collected in a prospective data base. Data of 360 patients were available for further analysis in 2011. All specimens of long-term survivors were histologically reviewed. RESULTS: Long-term survivors (n = 69) had a median survival of 91 months. Pathological re-evaluation of all specimens re-confirmed the diagnosis. Predictive factors for long-term survival in univariate analysis were no preoperative biliary stent, low CA 19-9 level, lack of blood transfusion, R0 resection, tumour diameter, and -grading, absence of lymph node or distant metastases, lymphangiosis, and perineural infiltration. Adjuvant chemotherapy showed a significant influence on overall survival but not on long-term survival. In multivariate analysis, lymph node ratio and volume of blood transfusion were predictors of long-term survival. CONCLUSION: Nearly 20% of patients with pancreas carcinoma who undergo surgical resection have a chance of long-term survival. Survival beyond 5 years is predicted by clinical and tumour-specific factors. Adjuvant chemotherapy might prolong overall survival but is, according to these results, unable to contribute to long-term survival. There is still a risk of recurrence after a 5- or even a 12-year mark. Survival beyond 5 or even 12 years, therefore, does not assure cure.

Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated. OBJECTIVE: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. DESIGN, SETTING, AND PATIENTS: CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. INTERVENTIONS: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up. RESULTS: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.

Malignancy in chronic pancreatitis: analysis of diagnostic procedures and proposal of a clinical algorithm.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis, and some benign conditions and syndromes, including chronic pancreatitis (CP), are risk factors for pancreatic carcinoma. However, the differential diagnosis of CP from PDAC is difficult for clinicians because PDAC frequently causes inflammation within the pancreas. Therefore, patients with CP exhibit not only an elevated risk of cancer, but they are also in danger of underdiagnosis. METHODS: The present study retrospectively analyzed 29 patients with pancreatic cancer who fulfilled our definition of "chronic pancreatitis" to identify characteristics to aid in the differential diagnosis between chronic pancreatitis with and without pancreatic cancer. All parameters were subjected to univariate analysis. RESULTS: We identified several factors that differed significantly between the CP patients and patients with CP and synchronous PDAC, and these characteristics were used to develop a diagnostic algorithm. The performance of the algorithm was externally validated in a different panel of patients from the Department of Surgery, Medical Faculty Mannheim. CONCLUSION: The present study succeeded in identifying characteristics that significantly differed in patients with and without PDAC in CP. These characteristics were integrated in a diagnostic algorithm that might help to improve diagnostic of PDAC in CP.