Formation of Nano- and Micro-Scale Surface Features Induced by Long-Range Femtosecond Filament Laser Ablation.

In this work, we study the characteristics of femtosecond-filament-laser-matter interactions and laser-induced periodic surface structures (LIPSS) at a beam-propagation distance up to 55 m. The quantification of the periodicity of filament-induced self-organized surface structures was accomplished by SEM and AFM measurements combined with the use of discrete two-dimensional fast Fourier transform (2D-FFT) analysis, at different filament propagation distances. The results show that the size of the nano-scale surface features increased with ongoing laser filament processing and, further, periodic ripples started to form in the ablation-spot center after irradiation with five spatially overlapping pulses. The effective number of irradiating filament pulses per spot area affected the developing surface texture, with the period of the low spatial frequency LIPSS reducing notably at a high pulse number. The high regularity of the filament-induced ripples was verified by the demonstration of the angle-of-incidence-dependent diffraction of sunlight. This work underlines the potential of long-range femtosecond filamentation for energy delivery at remote distances, with suppressed diffraction and long depth focus, which can be used in biomimetic laser surface engineering and remote-sensing applications.

Time-resolved visualization of high-repetition ultrashort pulse laser ablation.

A pump-probe setup including a Robert-cell-type delay stage is calculated and built in the presented study. The goal is to visualize laser beam material interactions upon highly repetitive ultrashort pulse irradiations by shadowgraph imaging, which makes a valuable contribution to clarify the occurring interaction phenomena in this field. Ultrashort laser pulses (λ=1030nm; τ H =400fs) are irradiated onto a bright-rolled stainless steel metal plate (AISI 316). The high-speed shadowgraph sequences are captured for the time-resolved imaging of plasma and shockwave evolution during material ablation. The captured time frame ranges from the time just before the next pulse irradiates the interaction zone until 2 µs after pulse irradiation. The first part of the experimental study features the shockwave dynamics and evolution of the laser plasma/ablation plume as induced upon single-pulse irradiations. It is shown that the expansion velocity of the shockwave decreases from 10 km/s shortly after pulse irradiation to 6.1 km/s at 41 ns after pulse irradiation. The second part deals with laser pulse trains by irradiating up to 10 pulses at 500 kHz pulse repetition frequency to the substrate. For increasing pulse numbers, the shadowgraphs show a steady increase in height and width of the laser plasma/ablation plume that were measured at 2.4 mm in height and 1.2 mm in width after the 10th pulse.

Quality of Life, Fatigue, and Sleep Problems in Pancreatic Cancer Patients­A Randomized Trial on the Effects of Exercise

BACKGROUND: Improving quality of life (QoL) is an important treatment goal in pancreatic cancer patients. Although the beneficial effects of exercise on QoL are well understood, few studies have investigated more aggressive cancers such as pancreatic cancer. METHODS: Within a randomized trial, we assessed the efficacy of 6-month resistance training on physical functioning (primary outcome) and further QoL-related outcomes. 65 pancreatic cancer patients were assigned to home-based training, supervised training, or a usual care control group. Analysis-of-covariance models on changes from baseline to 6 and 3 months were ap- plied. RESULTS: 47 patients completed the intervention period. After 6 months, no effects of resistance training were observed. However, after 3 months, explorative analyses showed significant between-group mean differences (MD) in favor for resistance training for physical functioning (pooled group: MD=11.0; p=0.016; effect size[ES]=0.31), as well as for global QoL (MD=12.1; p=0.016; effect size=0.56), and other outcomes, such as sleep problems and fatigue. Multiple imputation analyses yielded similar results. Home-based and supervised training performed similarly. CONCLUSION: This first randomized resistance training trial in pancreatic cancer patients indicated clinically relevant improve- ments in QoL after 3 but not after 6 months. Given the severity of pancreatic cancer, exercise recommendations may already commence at surgery.

Progressive Resistance Training to Impact Physical Fitness and Body Weight in Pancreatic Cancer Patients: A Randomized Controlled Trial.

OBJECTIVES: Maintaining or improving muscle mass and muscle strength is an important treatment goal in pancreatic cancer (PC) patients because of high risk of cachexia. Therefore, we assessed feasibility and effectivity of a 6-month progressive resistance training (RT) in PC patients within a randomized controlled trial. METHODS: Sixty-five PC patients were randomly assigned to either supervised progressive RT (RT1), home-based RT (RT2), or usual care control group (CON). Both exercise groups performed training 2 times per week for 6 months. Muscle strength for knee, elbow, and hip extensors and flexors and cardiorespiratory fitness and body weight were assessed before and after the intervention period. RESULTS: Of 65 patients, 43 patients were analyzed. Adherence rates were 64.1% (RT1) and 78.4% (RT2) of the prescribed training sessions. RT1 showed significant improvements in elbow flexor/extensor muscle strength and in maximal work load versus CON and RT2 (P < 0.05). Further, knee extensors were significantly improved for RT1 versus CON (P < 0.05). Body weight revealed no significant group differences over time. CONCLUSIONS: Progressive RT was feasible in PC patients and improved muscle strength with significant results for some muscle groups. Supervised RT seemed to be more effective than home-based RT.

Pylorus Resection Does Not Reduce Delayed Gastric Emptying After Partial Pancreatoduodenectomy: A Blinded Randomized Controlled Trial (PROPP Study, DRKS00004191).

OBJECTIVES: The aim of this study was to investigate the effect of pylorus resection on postoperative delayed gastric emptying (DGE) after partial pancreatoduodenectomy (PD). BACKGROUND: PD is the standard treatment for tumors of the pancreatic head. Preservation of the pylorus has been widely accepted as standard procedure. DGE is a common complication causing impaired oral intake, prolonged hospital stay, and postponed further treatment. Recently, pylorus resection has been shown to reduce DGE. METHODS: Patients undergoing PD for any indication at the University of Heidelberg were randomized to either PD with pylorus preservation (PP) or PD with pylorus resection and complete stomach preservation (PR). The primary endpoint was DGE within 30 days according to the International Study Group of Pancreatic Surgery definition. RESULTS: Ninety-five patients were randomized to PP and 93 patients to PR. There were no baseline imbalances between the groups. Overall, 53 of 188 patients (28.2%) developed a DGE (grade: A 15.5%; B 8.8%; C 3.3%). In the PP group 24 of 95 patients (25.3%) and in the PR group 29 of 93 patients (31.2%) developed DGE (odds ratio 1.534, 95% confidence interval 0.788 to 2.987; P = 0.208). Higher BMI, indigestion, and intraabdominal major complications were significant risk factors for DGE. CONCLUSIONS: In this randomized controlled trial, pylorus resection during PD did not reduce the incidence or severity of DGE. The development of DGE seems to be multifactorial rather than attributable to pyloric dysfunction alone. Pylorus preservation should therefore remain the standard of care in PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004191.

Cardiorespiratory fitness and muscle strength in pancreatic cancer patients.

PURPOSE: Cancer patients frequently experience reduced physical fitness due to the disease itself as well as treatment-related side effects. However, studies on physical fitness in pancreatic cancer patients are missing. Therefore, we assessed cardiorespiratory fitness and muscle strength of pancreatic cancer patients. METHODS: We included 65 pancreatic cancer patients, mostly after surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was used to evaluate isometric muscle strength. Physical fitness values were compared to reference values of a healthy population. Associations between sociodemographic and clinical variables with patients' physical fitness were analyzed using multiple regression models. RESULTS: Cardiorespiratory fitness (VO2peak, 20.5 ± 6.9 ml/min/kg) was significantly lower (-24%) compared to healthy reference values. In the 6MWT pancreatic cancer patients nearly reached predicted values (555 vs. 562 m). Maximal voluntary isometric contraction (MVIC) of the upper (-4.3%) and lower extremities (-13.8%) were significantly lower compared to reference values. Overall differences were larger in men than those in women. Participating in regular exercise in the year before diagnosis was associated with greater VO2peak (p < .05) and MVIC of the knee extensors (p < .05). CONCLUSIONS: Pancreatic cancer patients had significantly impaired physical fitness with regard to both cardiorespiratory function and isometric muscle strength, already in the early treatment phase (median 95 days after surgical resection). Our findings underline the need to investigate exercise training in pancreatic cancer patients to counteract the loss of physical fitness.

Enucleation: A treatment alternative for branch duct intraductal papillary mucinous neoplasms.

BACKGROUND: Small, asymptomatic, branch-duct intraductal papillary mucinous neoplasms of the pancreas are often kept under surveillance despite their malignant potential. The management of branch-duct intraductal papillary mucinous neoplasm is controversial with regard to indications and extent of any operative intervention. The present study aimed to evaluate enucleation as an alternative operative approach for branch-duct intraductal papillary mucinous neoplasms to exclude and prevent malignancy. METHODS: For branch-duct intraductal papillary mucinous neoplasms of <30 mm in diameter and an acceptable distance from the main pancreatic duct, enucleation was considered as the operative approach of choice. All patients scheduled for enucleation of branch-duct intraductal papillary mucinous neoplasm on the basis of these features between January 2004 and September 2014 were analyzed. Among these, patients with successful enucleation were compared with those who were scheduled for enucleation but converted intraoperatively to pancreatic resection (intention-to-treat analysis). End points were hospital morbidity and mortality as well as histopathology and functional outcome at a mean follow-up of 32 months. RESULTS: In the study, 115 patients with presumed branch-duct intraductal papillary mucinous neoplasm and the intention to perform pancreatic enucleation were included; 87 enucleations were performed in 74 patients. In 41 patients, enucleation was converted to a pancreatic resection (procedure-specific success rate 64%); indications for conversion included location or size (46%), presence of multicystic lesions (39%), or involvement of the main pancreatic duct (15%). Of the 74 patients with enucleation, 64 branch-duct intraductal papillary mucinous neoplasms revealed low- (85%), 11% moderate dysplasia-, and 4% high-grade dysplasia on histology. Among converted resections, 6 intraductal papillary mucinous neoplasms revealed high-grade dysplasia or invasive carcinoma (15%). Intention-to-treat analysis with patients converted to pancreatic resection showed that enucleations resulted in less blood loss (100 vs 400 mL) and a shorter operation time (146 vs 255 minutes; P < .001 each). Postoperative morbidity including postoperative pancreatic fistula was similar in both groups. No mortality occurred after enucleation; after formal resection, 1 patient died due to multiorgan failure. Both hospital stay (10 vs 14 days) and rates of postoperative endocrine and exocrine dysfunction rates were less after enucleation (P < .02 each). Intraductal papillary mucinous neoplasm-specific recurrence rates (3% vs 6%) were similar in both groups. CONCLUSION: Enucleation is a safe procedure that can be performed successfully in a high proportion of branch-duct intraductal papillary mucinous neoplasms and should be considered instead of standard resections as an important function-preserving alternative. Limitations may occur due to malignancy, size, localization, multilocularity, or main-duct involvement requiring conversion to a formal, anatomic resection. Beside the advantages in the short-term course, functional outcome seems to be superior after enucleation, and intraductal papillary mucinous neoplasm-specific recurrence rates are not increased compared with standard resections, at least at a mean follow-up of 32 months.

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). METHODS: This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. RESULTS: Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P < .004). CONCLUSION: Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government-sponsored, multicenter, randomized controlled PREBOT trial.

Pancreatic Cancer Surgery: The New R-status Counts.

OBJECTIVE: To assess the relevance of resection margin status for survival outcome after resection and adjuvant therapy for pancreatic cancer. BACKGROUND: The definitions for R0 and R1 margin status after resection for pancreatic cancer are controversial. The strict definition of R0 requiring a 1 mm tumor-free margin is not commonly accepted. Reported R0/R1 rates and associated survival are highly heterogeneous. METHODS: A standardized protocol with rigorous assessment of circumferential margins and the R0 definition with a 1 mm free margin were introduced into clinical routine in 2005. From a prospective database, patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma between January 1, 2006 and December 12, 2012 were identified. The rates of R0 (≥1 mm margin), R1 (<1 mm clearance), and R1 (direct margin involvement) status and associated survival were assessed by uni- and multivariable analyses. RESULTS: Of 561 patients included, 112 patients (20.0%) had R0 and 449 patients (80.0%) had R1 resections, including 123 (21.9%) R1 (≤1 mm) and 326 (58.1%) R1 (direct) resections. A total of 438 (85.9%) received adjuvant therapy. With R0, R1 (<1 mm), and R1 (direct) status the median survival times and 5-year survival rates were 41.6, 27.5, and 23.4 months; and 37.7%, 30.1%, and 20.3%, respectively (P < 0.0001). By multivariable analysis, margin status was confirmed to be independently associated with survival. CONCLUSIONS: In the context of adjuvant therapy, the resection margin status remains an important independent determinant of postresection survival. R0/R1 resection rates and associated survival vary significantly with the definitions used. An international consensus is urgently needed to achieve comparability with respect to studies and protocols on patients with adjuvant therapy.

Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients.

OBJECTIVE: For patients with locally advanced and unresectable pancreatic cancer (PDAC), neodadjuvant treatment and consecutive surgical exploration have been studied during the last decade with various neoadjuvant therapies including chemotherapy and combinations with radiation. Aim of the study was the evaluation of neoadjuvant therapy with a focus on Folfirinox. METHODS: All consecutive patients undergoing surgery for PDAC after neoadjuvant treatment were analyzed (clinico-pathological characteristics, secondary resection rates, outcome). Patients receiving Folfirinox were compared with other treatment regimens. RESULTS: Between December 2001 and June 2015, 575 patients received neoadjuvant treatment and were scheduled for resection after re-staging. A successful resection was achieved in 292 patients (50.8%). Resection rates following Folfirinox were 61% (76/125 patients) compared with 46% (150/322 patients) after gemcitabine and radiation, and 52% (66/128 patients) after other treatments (P = 0.026). Median overall survival was 15.3 months after resection vs 8.5 months after exploration alone (P < 0.0001). Subgroup median survival was 16.0 months (Folfirinox) vs 16.5 months (gemcitabine) and 14.5 months (others) with 3-year survival of 28.1%, 23.2%, and 19.7%, respectively (P = 0.8582). By multivariable analysis, Folfirinox was confirmed to be independently associated with a favorable prognosis. CONCLUSIONS: Folfirinox is a valuable treatment option in the neoadjuvant therapy of PDAC. From the present data, which represent the largest available study population to date, Folfirinox seems to be the most effective protocol resulting in a significantly better secondary resection rate and overall survival than other treatments. It should be considered in all patients fit for this regimen and consecutive surgical exploration.

Surgical ampullectomy: an underestimated operation in the era of endoscopy.

INTRODUCTION: Benign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater. PATIENTS AND METHODS: All patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success. RESULTS: Eighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%. CONCLUSION: TSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment.

Stimulation of Central α2 Receptors Attenuates Experimental Necrotizing Pancreatitis.

OBJECTIVES: Severe necrotizing pancreatitis (SNP) is a disease with relevant morbidity and mortality until today. No specific therapy is in sight. Central α2 agonists such as clonidine and dexmedetomidine are known to have anti-inflammatory effects though the cholinergic anti-inflammatory pathway and are implemented in the clinical routine as adjunct sedative drugs. Their potential effect on SNP has not yet been tested. METHODS: Severe necrotizing pancreatitis was induced in male Wistar rats. Four treatment groups received either clonidine or dexmedetomidine before (prophylactic) or after induction of SNP (therapeutic). After 12 hours, pancreatic morphologic injury, systemic proinflammatory high-mobility group box 1 protein, and pancreatic and pulmonary myeloperoxidase levels were evaluated. RESULTS: Severe necrotizing pancreatitis was fully established 12 hours after induction. "Prophylactic" and "therapeutic" administration of clonidine and dexmedetomidine reduced pancreatic morphologic injury (P < 0.05 vs SNP), serum proinflammatory high-mobility group box 1 protein (P < 0.0001 vs SNP), as well as pancreatic and pulmonary myeloperoxidase levels (P < 0.01 vs SNP). CONCLUSIONS: Prophylactic and therapeutic applications of the central α2 agonists clonidine and dexmedetomidine are effective to attenuate local and systemic injury in experimental SNP and should be evaluated in the clinical setting.

Postoperative pancreatic fistula: We need to redefine grades B and C.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most important complication after pancreatic surgery. In 2005, the International Study Group of Pancreatic Surgery (ISGPS) introduced a standardized POPF definition with severity grading from A to C. In recent years, interventional drainage (ID) has become the standard of care for symptomatic postoperative fluid collections or undrained POPF. From the original definition, it is unclear whether ID is categorized as POPF grade B or C. Therefore, international authors shift ID between grades B and C. The aim of the study was to analyze patients with ID (proposed new grade B) versus patients who underwent reoperation (grade C) for POPF. METHODS: Between 2005 and 2013, all patients undergoing pancreatic resection were analyzed regarding POPF grade A-C. Demographic data, type of operation, postoperative complications, therapies and outcome were examined with focus on ID versus reoperation. RESULTS: Of the 2,955 patients included, 403 developed POPF (13.6%). Among all POPF, 11% were grade A, 17% grade B (clinically symptomatic without ID), and 72% grade C. These patients underwent either ID (n = 165) or reoperation (n = 123). Patients with ID had an average hospital stay of 33 days and POPF-associated mortality of 0%. This was strikingly different from patients undergoing reoperation with a hospital stay of 47 days and POPF-associated mortality of 37% (P < .0001). CONCLUSION: After 10 years of the ISGPS classification, there is a clear-cut outcome difference between patients undergoing POPF-associated ID or reoperation. We propose assigning all patients undergoing ID as POPF grade B. Patients undergoing reoperation should definitely remain within category C.

Main-duct Intraductal Papillary Mucinous Neoplasm: High Cancer Risk in Duct Diameter of 5 to 9 mm.

OBJECTIVE: The 2012 international consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMN) recommend surgical treatment in main-duct IPMN patients with a main pancreatic duct (MPD) diameter of ≥10 mm. Aim of the present study was to analyze cancer risk in patients with an MPD diameter of less than 10 mm. METHODS: All consecutive patients (prospective data protocol) with histological proof of IPMN who underwent surgery between January 2004 and December 2013 were included in the study. Clinical characteristics, particularly preoperative imaging with regard to morphology of the MPD, were correlated with final histopathology. RESULTS: Among a total of 605 patients who underwent surgery for IPMN, there were 320 patients with MPD involvement, 238 patients with mixed-type IPMN, and 82 patients with main-duct IPMN alone. The total malignancy rate including high-grade dysplasia and invasive carcinoma in IPMNs with MPD involvement was 68%. When the MPD diameter was 5 to 9 mm, malignancy rate was 59%, whereas in MPD diameter more than 10 mm, it was 73%. No statistical correlations were observed between MPD diameter and clinical and/or IPMN features such as age, cyst location, mural nodules, serum tumor markers, or bilirubin. CONCLUSIONS: Main-duct IPMNs with a MPD between 5 and 9 mm already bear a significant risk of malignancy. Therefore, surgical treatment is clearly indicated in patients with a MPD diameter of ≥5 mm and the 2012 guidelines should be discussed and adapted with regard to this topic.

Current State of Vascular Resections in Pancreatic Cancer Surgery.

Pancreatic cancer (PDAC) is the fourth leading cause of cancer-related mortality in the Western world and, even in 2014, a therapeutic challenge. The only chance for long-term survival is radical surgical resection followed by adjuvant chemotherapy which can be performed in about 20% of all PDAC patients by the time of diagnosis. As pancreatic surgery has significantly changed during the past years, extended operations, including vascular resections, have become more frequently performed in specialized centres and the border of resectability has been pushed forward to achieve a potentially curative approach in the respective patients in combination with neoadjuvant and adjuvant treatment strategies. In contrast to adjuvant treatment which has to be regarded as a cornerstone to achieve long-term survival after resection, neoadjuvant treatment strategies for locally advanced findings are currently under debate. This overview summarizes the possibilities and evidence of vascular, namely, venous and arterial, resections in PDAC surgery.

Emergency pancreatic surgery--demanding and dangerous.

BACKGROUND: Elective pancreatic surgery can be carried out with mortality rates below 5% in specialized centers today. Only few data exist on pancreatic resections in emergency situations. The aim of the study was to characterize indications, procedures, and outcome of emergency pancreatic surgery in a tertiary center. METHODS: Prospectively collected data of all patients undergoing pancreatic operations at the authors' institution between October 2001 and December 2012 were analyzed regarding primary emergency operations in terms of indications, procedures, perioperative complications, and outcome. Emergency operations after preceding resections were excluded from the analysis. RESULTS: Twenty-three emergency operations were performed during the observation period. Indications were duodenal perforation (n = 8), upper GI bleeding (n = 6), complicated pseudocysts (n = 3), bile duct perforation (n = 2), pancreatic bleeding after blunt abdominal trauma (n = 1), pancreatic stent perforation (n = 1), necrotizing cholecystitis (n = 1), and ileus (n = 1). Procedures included partial and total duodeno-pancreatectomy (n = 15), cystojejunostomy (n = 2), distal pancreatectomy (n = 4), reconstruction of the ampulla Vateri (n = 1), and duodenectomy (n = 1). Median intraoperative blood loss was 750 (200-2500) ml and OP time 4.25 (1.75-9.25) h. Mean ICU stay was 21.3 (1-80) days with an overall surgical morbidity of 52.2%. Overall in-hospital mortality was 34.8% (8/23 pat.). CONCLUSIONS: Emergency pancreatic operations are infrequent and mainly performed due to duodenal perforation or bleeding; blunt abdominal trauma is rarely leading to emergency pancreas resections. They are associated with an increased morbidity and mortality and require a high level of surgical as well as interdisciplinary experience. Perioperative anesthesiological care and interventional radiological complication management are essential to improve outcome in this selective patient collective.

Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis.

PURPOSE: There is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival. METHODS: Patients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis. RESULTS: A total of 442 stage IV P-NET patients were identified, of whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of death = 0.41, 95 % confidence interval [CI] 0.25-0.66, p < 0.001) and cancer-specific survival (HR of death = 0.41, 95 % CI 0.25-0.67, p < 0.001) in unadjusted multivariate Cox regression analysis; the benefit persisted after propensity score adjustment. CONCLUSIONS: This population-based analysis of stage IV P-NET patients provides compelling evidence that palliative resection of the primary tumor is associated with significant survival benefit. Thus, the recent recommendations judging resection of the primary as inadvisable and the accompanying trend towards fewer palliative resections of the primary tumor have to be contested.

Inflammatory profiling of early experimental necrotizing pancreatitis.

AIMS: Inflammatory mediators play a pivotal role in severe necrotizing pancreatitis (SNP). Therapeutic approaches aim at the early inflammatory liberation of cytokines to avoid systemic complications. The present study evaluates the kinetics of inflammatory mediator release in SNP. MAIN METHODS: Experimental SNP was induced in male Wistar rats using the GDOC model. The animals were allocated into seven groups (n = 6/group). In group 1, sample harvesting was performed after sham operation while in groups 2-7 this was performed 1 h, 2 h, 4 h, 6 h, 9 h, and 12 h after initiation of SNP, respectively. Inflammatory mediator release,morphologic injury, and tissue MPO concentrations were evaluated between 1 and 12 h after induction. KEY FINDINGS: Pancreatic injury showed a continuous increase over the observation period (p b 0.05, respectively). MPO levels in the pancreas and lungs increased until 12 h after induction (p b 0.05, respectively). Antiinflammatory IL-10 showed an early peak and the pro-inflammatory mediators TNFα and IL-1ß peaked after 6 and 9 h, respectively (p b 0.05, respectively). HMGB1 levels constantly increased over time (p b 0.05, respectively). SIGNIFICANCE: The present study shows the release of relevant pro- and anti-inflammatory mediators in SNP for the first time in one single experimental setup. Inflammatory mediators peak within the first few hours after SNP induction. Consequently, the effect of therapeutic approaches on early changes in cytokine release should be evaluated later than 2 h after initiation.

Pancreatic main-duct involvement in branch-duct IPMNs: an underestimated risk.

OBJECTIVES: This study aimed to analyze a large single-center population of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas with respect to risk factors of malignant transformation. BACKGROUND: There is international consensus that main-duct (MD) as well as mixed-type IPMNs should be treated surgically due to a high risk of malignancy. In contrast, there is an ongoing controversy about surgery of branch-duct type IPMN (BD-IPMN). METHODS: All consecutive patients who underwent surgery for IPMN between January 2004 and December 2012 were included. Clinical characteristics and preoperative imaging were correlated with histopathological features. RESULTS: A total of 512 patients underwent pancreatic surgery and had a histological proof of IPMN. According to preoperative imaging, 74 patients had MD-IPMN (14%), 205 mixed-type (40%), and 233 suspected BD-IPMN (46%). On histopathology, 162 of 512 patients revealed low-grade, 105 moderate, and 52 high-grade dysplasia. One hundred ninety-three IPMN patients (38%) suffered from invasive carcinoma. Among invasive IPMNs, the majority (58%) were mixed-type lesions according to preoperative imaging. Of 141 Sendai negative BD-IPMNs, a malignancy rate of 18% (high-grade dysplasia and invasive carcinoma) was found. Most interesting, 29% of suspected BD-IPMNs (67/233) revealed histological involvement of the main pancreatic duct not evident in preoperative imaging. CONCLUSIONS: All subtypes of IPMNs display a relevant risk for malignant transformation. By abdominal imaging, many IPMNs are misclassified as BD-IPMNs but reveal mixed-type lesions in histopathology. Because currently available preoperative diagnostics are not sufficient to reliably diagnose BD-IPMNs, surgical resection for suspected small branch-duct IPMN should be considered in patients fit for surgery.

Acute alcohol-induced pancreatic injury is similar with intravenous and intragastric routes of alcohol administration.

OBJECTIVES: Five percent of alcoholics develop an acute pancreatitis (AP). The mechanism leading to pancreatic injury is not yet understood. Microcirculatory disorders seem to play a pivotal role. The objective of this study was to compare alcoholic pancreatic injury in response to intravenous and intragastric routes of alcohol administration. METHODS: Alcohol was applied in rats intravenously (IV) or gastric via a surgical implanted feeding tube (IG). Serum alcohol concentration was maintained between 1.5‰ and 2.5‰. Four subgroups (n = 6/group) were examined in the IV/IG arm and compared with healthy controls. Pancreatic microcirculation, enzyme levels, and morphological damage were assessed after 3, 6, 12, and 24 hours. RESULTS: Microcirculatory analysis showed significantly disturbed pancreatic perfusion and increased adherent leukocytes in IV and IG animals. In IV and IG groups, serum amylase was increased without morphological signs of AP compared with healthy controls. CONCLUSIONS: Alcohol application does not induce AP in rodents, but impairs pancreatic microcirculation irrespectively of the application route. Intravenous application is commonly used and shows no disadvantages compared with the physiological intragastric application form. Therefore, the intravenous route offers a valid model, which mimics the physiological process for further studies of the influence of acute alcohol intoxication on the pancreas.