Deep Learning Auto-Segmentation Network for Pediatric Computed Tomography Data Sets: Can We Extrapolate From Adults?

PURPOSE: Artificial intelligence (AI)-based auto-segmentation models hold promise for enhanced efficiency and consistency in organ contouring for adaptive radiation therapy and radiation therapy planning. However, their performance on pediatric computed tomography (CT) data and cross-scanner compatibility remain unclear. This study aimed to evaluate the performance of AI-based auto-segmentation models trained on adult CT data when applied to pediatric data sets and explore the improvement in performance gained by including pediatric training data. It also examined their ability to accurately segment CT data acquired from different scanners. METHODS AND MATERIALS: Using the nnU-Net framework, segmentation models were trained on data sets of adult, pediatric, and combined CT scans for 7 pelvic/thoracic organs. Each model was trained on 290 to 300 cases per category and organ. Training data sets included a combination of clinical data and several open repositories. The study incorporated a database of 459 pediatric (0-16 years) CT scans and 950 adults (>18 years), ensuring all scans had human expert ground-truth contours of the selected organs. Performance was evaluated based on Dice similarity coefficients (DSC) of the model-generated contours. RESULTS: AI models trained exclusively on adult data underperformed on pediatric data, especially for the 0 to 2 age group: mean DSC was below 0.5 for the bladder and spleen. The addition of pediatric training data demonstrated significant improvement for all age groups, achieving a mean DSC of above 0.85 for all organs in every age group. Larger organs like the liver and kidneys maintained consistent performance for all models across age groups. No significant difference emerged in the cross-scanner performance evaluation, suggesting robust cross-scanner generalization. CONCLUSIONS: For optimal segmentation across age groups, it is important to include pediatric data in the training of segmentation models. The successful cross-scanner generalization also supports the real-world clinical applicability of these AI models. This study emphasizes the significance of data set diversity in training robust AI systems for medical image interpretation tasks.

Incisional hernia repair following pancreatic surgery-open vs laparoscopic approach.

INTRODUCTION: For pancreatic procedures, transverse and midline or combined approaches are used. Having an increased morbidity after pancreatic surgery, these patients have an increased risk of developing an incisional hernia. In the following, we will analyze how the results of incisional hernia surgery after pancreatic surgery are presented in the Herniamed Registry. METHODS: Hospitals and surgeons from Germany, Austria and Switzerland can voluntarily enter all routinely performed hernia operations prospectively into the Herniamed Registry. All patients sign a special informed consent declaration that they agree to the documentation of their treatment in the Herniamed Registry. Perioperative complications (intraoperative complications, postoperative complications, complication-related reoperations and general complications) are recorded up to 30 days after surgery. After 1, 5, and 10 years, patients and primary care physicians are contacted and asked about any pain at rest, pain on exertion, chronic pain requiring treatment or recurrence. This retrospective analysis of prospectively collected data compares the outcomes of minimally invasive vs open techniques in incisional hernia repair after pancreatic surgery. RESULTS: Relative to the total number of all incisional hernia patients in the Herniamed Registry, the proportion after pancreatic surgery with 1-year follow-up was 0.64% (n = 461) patients. 95% of previous pancreatic surgeries were open. Minimally invasive incisional hernia repair was performed in 17.1% and open repair in 82.9% of cases. 23.2% of the defects were larger than 10 cm and 32.8% were located laterally or were a combination of lateral and medial defects. Among the few differences between the collectives, a significantly higher rate of defect closure (58.1% vs 25.3%; p < 0.001) and drainage (72.8% vs 13.9%; p < 0.001) was found in the open repairs, and larger meshes were seen in the minimally invasive procedures (340.6 cm2 vs 259.6 cm2; p < 0.001). No difference deemed a risk factor for chronic postoperative pain was seen in the rate of preoperative pain between the open and minimally invasive procedures (Appendix Table 4) No significant differences were found in either the perioperative complications or at 1-year follow-up. CONCLUSIONS: Incisional hernias after complex pancreatic surgery can be repaired safely and with a low recurrence rate in both open and minimally invasive techniques.

Evaluating synthetic computed tomography images for adaptive radiotherapy decision making in head and neck cancer.

Background and purpose: Adaptive radiotherapy (ART) decision-making benefits from dosimetric information to supplement image inspection when assessing the significance of anatomical changes. This study evaluated a dosimetry-based clinical decision workflow for ART utilizing deformable registration of the original planning computed tomography (CT) image to the daily Cone Beam CT (CBCT) to replace the need for a replan CT for dose estimation. Materials and methods: We used 12 retrospective Head & Neck patient cases having a ground truth - a replan CT (rCT) in response to anatomical changes apparent in the daily CBCT - to evaluate the accuracy of dosimetric assessment conducted on synthetic CTs (sCT) generated by deforming the original planning CT Hounsfield Units to the daily CBCT anatomy.The original plan was applied to the sCT and dosimetric accuracy of the sCT was assessed by analyzing plan objectives for targets and organs-at-risk compared to calculations on the ground-truth rCT. Three commercial DIR algorithms were compared. Results: For the best-performing algorithms, the majority of dose metrics calculated on the sCTs differed by less than 4 Gy (5.7% of 70 Gy prescription dose). An uncertainty of ±2.5 Gy (3.6% of 70 Gy prescription) is recommended as a conservative tolerance when evaluating dose metrics on sCTs for head and neck. Conclusions: Synthetic CTs present a valuable addition to the adaptive radiotherapy workflow, and synthetic CT dose estimates can be effectively used in addition to the current practice of visually inspecting the overlay of the planning CT and CBCT to assess the significance of anatomical change.

Laparoscopic transversus abdominis release for complex ventral hernia repair: technique and initial findings.

PURPOSE: The open Rives-Stoppa retrorectus and transversus abdominis release (TAR) techniques are well established in open ventral and incisional hernia repair. The principles are currently being translated into minimally invasive surgery with different concepts. In this study, we investigate our initial results of transperitoneal laparoscopic TAR for ventral incisional hernia repair (laparoscopic TAR). METHODS: Over a 20-month period, 23 consecutive patients with incisional hernias underwent surgery. Laparoscopic TAR was performed transperitoneally with adhesiolysis from the anterior abdominal wall, development of the retrorectus space and TAR, midline reconstruction and extraperitoneal mesh reinforcement. RESULTS: There were 23 incisional hernias, of which 70% were M2-M4 and 60% were W3. Median patient age was 68 years and the median BMI was 31. Median operating time was 313 min, and hospital stay was 4 days. Morbidity was 26% (Clavien-Dindo 1: n = 4 and 2 + 3b: n = 2). CONCLUSION: With the laparoscopic TAR, it was possible to treat a series of patients with ventral incisional hernias. The operating times were long. However, with a low rate of perioperative complications the hospital stay was short As feasibility is demonstrated, the clinical relevance of the method has to be further evaluated.

Selection of motion management in liver stereotactic body radiotherapy and its impact on treatment time.

Background and purpose: Reduction of respiratory tumour motion is important in liver stereotactic body radiation therapy (SBRT) to reduce side effects and improve tumour control probability. We have assessed the distribution of use of voluntary exhale breath hold (EBH), abdominal compression (AC), free breathing gating (gating) and free breathing (FB), and the impact of these on treatment time. Materials and Methods: We assessed all patients treated in a single institution with liver SBRT between September 2017 and September 2021. Data from pre-simulation motion management assessment using fluoroscopic assessment of liver dome position in repeat breath holds, and motion with and without AC, was reviewed to determine liver dome position consistency in EBH and the impact of AC on motion. Treatment time was assessed for all fractions as time from first image acquisition to last treatment beam off. Results: Of 136 patients treated with 145 courses of liver SBRT, 68 % were treated in EBH, 20 % with AC, 7 % in gating and 5 % in FB. AC resulted in motion reduction < 1 mm in 9/26 patients assessed. Median treatment time was higher using EBH (39 min) or gating (42 min) compared with AC (30 min) or FB (24 min) treatments. Conclusions: Motion management in liver SBRT needs to be assessed per-patient to ensure appropriate techniques are applied. Motion management significantly impacts treatment time therefore patient comfort must also be taken into account when selecting the technique for each patient.

Genome-wide mapping of somatic mutation rates uncovers drivers of cancer.

Identification of cancer driver mutations that confer a proliferative advantage is central to understanding cancer; however, searches have often been limited to protein-coding sequences and specific non-coding elements (for example, promoters) because of the challenge of modeling the highly variable somatic mutation rates observed across tumor genomes. Here we present Dig, a method to search for driver elements and mutations anywhere in the genome. We use deep neural networks to map cancer-specific mutation rates genome-wide at kilobase-scale resolution. These estimates are then refined to search for evidence of driver mutations under positive selection throughout the genome by comparing observed to expected mutation counts. We mapped mutation rates for 37 cancer types and applied these maps to identify putative drivers within intronic cryptic splice regions, 5' untranslated regions and infrequently mutated genes. Our high-resolution mutation rate maps, available for web-based exploration, are a resource to enable driver discovery genome-wide.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Outcome of ambulatory video-EEG monitoring in a ˜10,000 patient nationwide cohort.

PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.

Coeliac disease in Caucasian and South Asian patients in the North West of England.

BACKGROUND: Coeliac disease is an autoimmune enteropathy characterised by mucosal inflammation subsequent to gluten exposure, leading to malabsorption. Treatment is strict dietary control, relying on the patient's ability to maintain lifestyle modifications. The present study aimed to compare clinical presentation and adherence to a gluten-free diet between South Asian and Caucasian patients with coeliac disease in East Lancashire METHODS: In total, 33 South Asian and 113 Caucasian adult patients diagnosed with coeliac disease under the care of the Dietetics Department at East Lancashire Hospitals NHS Trust were selected using a convenience sampling method and then allocated to the South Asian or Caucasian group. A subjective assessment of dietetic notes from follow-up visits within 1 year of the first appointment was undertaken by two investigators who subsequently allocated the patients to one of the three categories: (i) fully-adherent; (ii) partly-adherent; and (iii) non-adherent. Presenting complaint, vitamin D, vitamin B12 , folate and ferritin levels were also compared. RESULTS: There was a significant difference in adherence to gluten-free diet between the groups, with a larger proportion of Caucasian patients being fully adherent to gluten-free diet compared to South Asian patients (64.6% versus 12.1%, P < 0.001). In addition, a significantly higher proportion of South Asian patients were vitamin D deficient compared with Caucasian patients (70.8% versus 32.8%, P = 0.002). CONCLUSIONS: The rates of strict adherence to gluten-free diet and vitamin D levels were significantly lower in South Asian patients with coeliac disease compared to the Caucasian coeliac population. Further studies are required to investigate the causes and improve adherence in the South Asian population.

[Symptoms, Diagnostics, Treatment and Classification of 22 Patients with Postpancreatectomy Haemorrhage (PPH) in a Series of 400 Consecutive Pancreatic Head Resections and Pancreatectomies]. / Symptomatik, Diagnostik, Therapie und Klassifikation von 22 Patienten mit Postpankreatektomie-Hämorrhagien (PPH) in einer Serie von 400 konsekutiven Pankreaskopfresektionen und Pankreatektomien.

Introduction: Postpancreatectomy haemorrhage (PPH) is a dangerous complication after pancreatic resection. Patients and Methods: From 2006 to 2015, 400 consecutive pancreatic head resections and pancreatectomies were performed and prospectively documented. This study analysed incidence, treatment and outcome of patients with PPH. Results: Incidence of PPH was 5.5 % (n = 22). PPH occurred in a median of eight days after pancreatic surgery with an equal frequency of symptoms being caused by gastrointestinal bleeding (n = 11) and abdominal bleeding (n = 11). Postoperative pancreatic fistulas (POPF) were significantly more frequent in case of PPH (45 % POPF in case of PPH vs. 20 % POPF in case of no PPH, p < 0.01). PPH was more frequent after pancreatogastrostomy (8/70; 11 %) than after pancreatojejunostomy (11/281; 4 %; p = 0.01). The majority of bleedings after pancreatogastrostomy came from the intragastric cut surface of the pancreas. During the first week, relaparotomy was significantly more frequent (n = 5; 56 %) than in late PPH (n = 1; 8 %; p = 0.01). In late PPH, interventions (angiography; n = 7, endoscopy; n = 4) were more frequent. In 16 severe cases, surgical/interventional bleeding control (n = 12) or relevant transfusions of more than 3 units of packed red blood cells (n = 4) were performed. Compared with the whole group, mortality was significantly increased in case of PPH (13.6 % in case of PPH vs. 3.7 % in case of no PPH; p = 0.03). Conclusion: PPH is an episodic and potentially life-threatening complication with an increased mortality rate, which is frequently associated with impaired healing of the pancreatic anastomosis. Diagnostic investigation and treatment of PPH requires an experienced surgical centre with a close cooperation with endoscopy and (interventional) radiology.

[Impact of Age and Comorbidity on Perioperative Mortality after 250 Pancreatic Head Resections]. / Einfluss des Lebensalters und der Begleiterkrankungen auf die perioperative Mortalität nach 250 Pankreaskopfresektionen.

INTRODUCTION: In line with the current demographic development, elderly patients make up an increasing proportion of surgical patients. It is still unclear under which conditions pancreatic surgery can be performed with low mortality in these patients. PATIENTS AND METHODS: From 2009 to 2014, 250 consecutive pancreatoduodenectomies (PDs) were performed in a non-university hospital. Perioperative data were documented prospectively. Based on median patient age (< 70 years vs. ≥ 70 years), a retrospective analysis of perioperative morbidity and mortality was performed. In addition, subgroup analyses were conducted. RESULTS: Older patients had a significantly higher frequency of cardiovascular comorbidities (p = 0.04), diabetes mellitus (p = 0.01), impaired renal function (p = 0.01) and a higher ASA classification (p < 0.01). Also, surgical procedures due to malignancy were significantly more common in this group (p < 0.01). Morbidity was equally high in both groups (< 70 years: 57 % vs. ≥ 70 years: 65 %; p = 0.02). Mortality was significantly higher in patients over 70 years of age (< 70 years: 1.4 % vs. ≥ 70 years: 9.1 %; p < 0.01). In a multivariate analysis, only liver cirrhosis (p < 0.01) and age (≥ 70 years; p = 0.04) were independent risk factors for postoperative mortality. However, it was also demonstrated that, under certain conditions, even much older patients (≥ 80 years; n = 34) may be subjected to surgery with a low mortality (3 %). DISCUSSION: In elderly patients, PD is more frequently indicated in cases of malignancy. All in all, perioperative mortality in patients over 70 years of age is significantly elevated. Under certain conditions, however, even much older patients may safely undergo pancreatic surgery.

Cycling Time Trial Performance 4 Hours After Glycogen-Lowering Exercise Is Similarly Enhanced by Recovery Nondairy Chocolate Beverages Versus Chocolate Milk.

Postexercise chocolate milk ingestion has been shown to enhance both glycogen resynthesis and subsequent exercise performance. To assess whether nondairy chocolate beverage ingestion post-glycogen-lowering exercise can enhance 20-km cycling time trial performance 4 hr later, eight healthy trained male cyclists (21.8 ± 2.3y, VO2max = 61.2 ± 1.4 ml·kg-1·min-1; M ± SD) completed a series of intense cycling intervals designed to lower muscle glycogen (Jentjens & Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling time trial. During the first 2 hr of recovery, participants ingested chocolate dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened, flavored beverage (PLACEBO) at 30-min intervals in a double-blind, counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ) were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g CHO·kg body mass-1·h-1. Fluid intake across treatments was equalized (2,262 ± 148 ml) by ingesting appropriate quantities of water based on drink intake. The CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and HEMPCHOC, respectively. One-way analysis of variance with repeated measures showed time trial performance (DAIRYCHOC = 34.58 ± 2.5 min, SOYCHOC = 34.83 ± 2.2 min, HEMPCHOC = 34.88 ± 1.1 min, MILK = 34.47 ± 1.7 min) was enhanced similarly vs PLACEBO (37.85 ± 2.1) for all treatments (p = .019) These data suggest that postexercise macronutrient and total energy intake are more important for same-day 20-km cycling time trial performance after glycogen-lowering exercise than protein type or protein-to-carbohydrate ratio.

[Computed Tomography-Based Planimetry of the Pancreatic Transection Line in Risk Evaluation for Postoperative Pancreatic Fistula after Pancreatic Head Resection]. / Orthograde Planimetrie der Pankreasschnittfläche anhand der präoperativen Computertomografie zur Risikoeinschätzung einer postoperativen Pankreasfistel nach Pankreaskopfresektion.

BACKGROUND: Postoperative pancreatic fistula is a relevant complication after pancreatoduodenectomy. Therefore, preoperative detection of high risk patients may be important. We evaluated preoperative CT-imaging by planimetry at the expected resection plane along the superior mesenteric vein and correlated the results with the incidence of postoperative pancreatic fistula. PATIENTS AND METHODS: From 2009 to 2013, 123 patients with pancreatoduodenectomy underwent homogenous preoperative imaging and reconstruction of the pancreatojejunostomy. Planimetry was performed at a multiplanar reconstruction of the pancreatic transection plane (diameter, range, duct width, area) as well as the calculation of ratios (duct width/pancreatic diameter; D/P-ratio). The measured values were correlated with the incidence of postoperative pancreatic fistula. RESULTS: Planimetry showed a significant difference of the pancreatic transection plane in relation to the incidence of postoperative pancreatic fistula. A thick parenchyma and a tiny duct are significant risk factors. In 84 % or, respectively, 94 % of the patients with postoperative pancreatic fistula, a duct width of less than 20 % of the pancreatic diameter was observed (D/P ratio < 0.2; p < 0.01). The D/P ratio was the only independent risk factor in multivariate analysis. DISCUSSION: The incidence of postoperative pancreatic fistula correlates significantly with the morphology of the pancreatic transection plane. The risk increases significantly with a D/P ratio of < 0.2.

[Pancreatojejunostomy in pancreatic head resection using a resorbable monofilament for internal drainage of the anastomosis - clinical experience and perioperative results]. / Pankreatojejunostomie bei der Pankreaskopfresektion unter Verwendung eines resorbierbaren monofilen Fadens zur inneren Schienung der Anastomose - klinische Erfahrungen und perioperative Ergebnisse.

BACKGROUND: Pancreatic fistulas are relevant in perioperative outcome, morbidity and mortality after pancreatic head resection. We analysed the potential benefit of an internal pancreatic duct draining technique by a resorbable monofilament suture if performing a two-layer duct-to-mucosa pancreatojejunostomy. PATIENTS AND METHODS: From 2006 to 2010, 139 pancreatic head resections were performed in our department (124 pylorus-preserving, 15 Whipple). Indications for surgery were malignancies (n = 97), chronic pancreatitis (n = 24) or others (n = 18). In 64 cases, internal drainage of the pancreatic anastomosis was performed as described. Perioperative results were evaluated by the ISGPF classification (International Study Group for Pancreatic Fistula, type A-C) and Accordion classification (degree 1-6). RESULTS: Pancreatic anastomosis was performed in 99 cases as pancreatojejunostomy and in 41 cases as pancreatogastrostomy. Morbidity (Accordion 1-6) was 48 %, and mortality was 5.8 %. Pancreatic fistulas (A-C) occurred in 27 (19.4 %) cases. Only one patient died as a direct consequence of a pancreatic fistula (type C fistula after pylorus-preserving pancreatic head resection and pancreatogastrostomy). In the subgroup of patients with a two-layer duct-to-mucosa pancreatojejunostomy with internal pancreatic duct drainage by a resorbable monofilament suture (n = 64), a pancreatic fistula occurred in 20.3 % (n = 13). According to the ISGPF classification, they were type A (n = 10), type B (n = 2) and type C fistulas (n = 1). In this subgroup with pancreatic duct drainage, morbidity (Accordion 1-6) was 55 % (n = 35) and mortality (Accordion 6) was 6.2 % (n = 4). Complications due to the pancreatic duct drainage were not observed. CONCLUSION: Internal drainage of the duct-to-mucosa pancreatojejunostomy using monofilament suture material is a safe and feasible method. Pancreatic fistula occurred in 20 % both in the entire group as well as in subgroups with or without pancreatic duct drainage. A reduction of the rate of pancreatic fistula could not be achieved by internal drainage of the pancreatojejunostomy.

Characterization of surface stiffness and probe-sample dissipation using the band excitation method of atomic force microscopy: a numerical analysis.

Recently Jesse and co-workers introduced the band excitation atomic force microscopy (BE-AFM) method (Jesse et al 2007 Nanotechnology 18 435503), in which the cantilever probe is excited in a continuum frequency band in order to measure its response at all frequencies in the band. Analysis of the cantilever response using the damped harmonic oscillator model provides information on the stiffness and level of dissipation at the tip-sample junction as the sample is scanned. Since its introduction, this method has been used in magnetic, electromechanical, thermal and molecular unfolding applications, among others, and has given rise to a new family of scanning probe microscopy techniques. Additionally, the concept is applicable to any field in which measurement of the frequency response of harmonic oscillators is relevant. In this paper we present an analytical and numerical analysis of the excitation signals used in BE-AFM, as well as of the cantilever response under different conditions. Our analysis is performed within the context of viscoelastic characterization. We discuss subtleties in the cantilever dynamics, provide guidelines for implementing the method effectively and illustrate the use of simulation in interpreting the results.

A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging.

Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity was tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence measurement mediated by the stable integration of the luciferase gene was employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg), Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor growth, as measured via in vivo bioluminescence, reducing the primary tumor size by 68% (SD +/- 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (-7%; +/- 1.5%). In 80% of animals, luciferase activity in the liver indicated the presence of metastases. All treatments, including the empty liposomes, reduced the metastatic burden. Thus, GemLip shows promising antitumoral activity in this model. Surprisingly, empty liposomes attenuate the spread of metastases similar to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful tool to observe tumor growth in vivo, and to detect and quantify metastases.

[Does hospital volume have influence on the results of pancreatic surgery?]. / Beeinflussen Mindestmengen die Ergebnisse der Pankreaschirurgie?

Hospital volume is one of the most discussed but also disputed subjects of surgery during the recent years. In no other surgical entity as in pancreatic surgery the number of performed operations has as much influence on morbidity and mortality. Despite of decreasing mortality, morbidity in pancreatic surgery remains relatively high even in specialized centres. Numerous studies demonstrated a reduction of perioperative mortality in centres with more than 10 patients per year by over 50%. In our own collective we demonstrated a significant reduction of mortality by 4% to 1% in two successive periods and a significant reduction of morbidity from 47% to 35%. We review the factors that are held responsible for decreasing mortality and complication rate in specialized centres and review published studies on this subject up to date. Our results confirm studies form other countries that increasing centre experience as well as operations performed in high volume hospitals decrease the complication rate and mortality after pancreatic head resection.

[Portal vein embolization preparation for major hepatic resection: a new standard in liver surgery]. / Partielle Pfortaderembolisation als Vorbereitung zur ausgedehnten Leberteilresektion: eine interdisziplinäre Herausforderung.

Preoperative portal vein embolization (PVE) is increasingly used for operative treatment of patients scheduled to undergo liver resection when the volume of the future remnant liver appears to be insufficient. Portal vein embolization should be considered when the prospective postoperative liver volume is less than 20 % or less than 40 % in patients with known liver cirrhosis. Our own results (n = 28) demonstrated an average volume increase in segments II and III of 280 +/- 95 ml to 420 +/- 98 ml within 6 weeks after selective percutaneous- transhepatic embolization of the portal vein branches (IV)-V-VIII. Thus, an expanded right resection of the liver could be performed in all patients without major complications. None of the patients suffered from clinically relevant liver insufficiency within the first few postoperative months.

MMP-9 in serum correlates with the development of pulmonary complications in experimental acute pancreatitis.

INTRODUCTION: The prediction of the course of acute pancreatitis and its arising complications is of clinical importance. The aim of this study was to judge the time course and relevance of matrix metalloproteinase-9 (MMP-9), a PMN-derived protease, for the development of pulmonary complications in two models of acute pancreatitis. METHODS: MMP-9 was evaluated in a standardized experimental model of acute pancreatitis. Mild edematous (n = 12) and severe necrotizing pancreatitis (n = 48) were induced by intravenous cerulein or intravenous cerulein and intraductal application of glycodeoxycholic acid and compared to control animals. 1, 6, 9, 12, 24 and 72 h after induction, rats were sacrificed and damage to the lung and the pancreas was quantified by histology and extravasation of Evans blue. At 1, 6, 9, 12, 24 and 72 h, we determined MMP-9 in serum by ELISA. RESULTS: In our model, MMP-9 in serum was increased in the group with severe acute pancreatitis in comparison to mild edematous pancreatitis and controls at each evaluated time point (p < 0.05). The maximum release of MMP-9 preceded the development of pulmonary complications, verified by histology and extravasation of Evans blue. MMP-9 showed a negative predictive value of 96.2% and a positive predictive value of 100% for the development of pulmonary complications. CONCLUSION: MMP-9 in serum allows a valid grouping to severe and mild courses of experimental acute pancreatitis with a good predictive value for the development of pulmonary complications. MMP-9 should be evaluated as a valid single marker for the prediction of progression and the development of pulmonary complications in acute pancreatitis in clinical studies.

[Therapeutic splitting as standard treatment for cholelithiasis]. / Cholelithiasis: Therapeutisches Splitting als Standard?

At the moment, therapeutic splitting is still regarded by the vast majority of surgeons as the gold standard for stones in the common bile duct. Endoscopic clearance of the duct certainly is much less invasive than open exploration. However, this does not apply when compared with laparoscopic stone removal. Both are equivalent in respect to stone clearance rates, but the laparoscopic techniques protect patients from the long-term sequelae of endoscopic papillotomy. This can be important particularly for younger patients. Laparoscopic bile duct exploration is cost-effective and safe. Special experience in laparoscopic surgical techniques, however, is mandatory. Thus, surgeons should intensify their training in laparoscopic bile duct exploration in order to increase the acceptance of these techniques.