Meta-analysis of recurrence pattern after resection for pancreatic cancer.

BACKGROUND: Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors. METHODS: MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated. RESULTS: Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07). CONCLUSION: Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.

ANTECEDENTES: El mapeo del patrón de recidiva inicial tras la resección de un adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) podría ayudar a estratificar subpoblaciones de pacientes para un seguimiento postoperatorio óptimo. El objetivo de esta revisión sistemática con metaanálisis fue investigar los patrones de recidiva inicial de PDAC y correlacionarlos con factores clínico-patológicos. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE y Web of Science para seleccionar estudios que presentaran información sobre los patrones de recidiva inicial después de la resección del PDAC. Se extrajeron los datos de los estudios seleccionados para su inclusión en el metaanálisis. Se calcularon las razones de oportunidades agrupadas (pooled odds ratio, OR) y los i.c. del 95% para definir los factores clínico-patológicos relacionados con las localizaciones de la recidiva. Se estimó el promedio ponderado de la mediana de la supervivencia global. RESULTADOS: Se incluyeron 89 estudios con 17.313 pacientes a los que se realizó una resección por PDAC. Las tasas medias ponderadas de las localizaciones de la recidiva inicial fueron del 20,8% para la locorregional, 26,5% para las hepáticas, 11,4% para el pulmón y 13,5% para la diseminación peritoneal. La mediana ponderada de supervivencia global fue de 19,8 meses (locorregional), 15,0 meses (hígado), 30,4 meses (pulmón) y 14,1 meses (diseminación peritoneal). El metaanálisis demostró que la resección R1 (inicial) (OR 2,21, i.c. del 95% 1,12-4,35), la invasión perineural (OR 5,19; i.c. del 95% 2,79-9,64) y la positividad de la citología del lavado peritoneal (OR 5,29; i.c. del 95% 3,03-9,25) se asociaron significativamente con la diseminación peritoneal como localización de recidiva inicial. El bajo grado de diferenciación tumoral se asoció significativamente con la recidiva hepática (OR 4,15; i.c. del 95%: 1,71-10,07). CONCLUSIÓN: Se podrían tener en cuenta estos factores de riesgo de los patrones de recidiva tras la cirugía para realizar un seguimiento y tratamiento específicos en pacientes con cáncer de páncreas.

Meta-analysis of effect of routine enteral nutrition on postoperative outcomes after pancreatoduodenectomy.

BACKGROUND: The optimal nutritional treatment after pancreatoduodenectomy is still unclear. The aim of this meta-analysis was to investigate the impact of routine enteral nutrition following pancreatoduodenectomy on postoperative outcomes. METHODS: RCTs comparing enteral nutrition (regular oral intake with routine tube feeding) with non-enteral nutrition (regular oral intake with or without parenteral nutrition) after pancreatoduodenectomy were sought systematically in the MEDLINE, Cochrane Library and Web of Science databases. Postoperative data were extracted. Random-effects meta-analyses were performed to compare postoperative outcomes in the two arms, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 per cent confidence intervals. In subgroup analyses, the routes of nutrition were assessed. Percutaneous tube feeding and nasojejunal tube feeding were each compared with parenteral nutrition. RESULTS: Eight RCTs with a total of 955 patients were included. Enteral nutrition was associated with a lower incidence of infectious complications (OR 0·66, 95 per cent c.i. 0·43 to 0·99; P = 0·046) and a shorter length of hospital stay (MD -2·89 (95 per cent c.i. -4·99 to -0·80) days; P < 0·001) than non-enteral nutrition. Percutaneous tube feeding had a lower incidence of infectious complications (OR 0·47, 0·25 to 0·87; P = 0·017) and a shorter hospital stay (MD -1·56 (-2·13 to -0·98) days; P < 0·001) than parenteral nutrition (3 RCTs), whereas nasojejunal tube feeding was not associated with better postoperative outcomes (2 RCTs). CONCLUSION: As a supplement to regular oral diet, routine enteral nutrition, especially via a percutaneous enteral tube, may improve postoperative outcomes after pancreatoduodenectomy.

[Prevention of postoperative infections : Evidence-based principles]. / Vermeidung postoperativer Infektionen : Evidenzbasierte Prinzipien.

BACKGROUND: Surgical site infections (SSI) are one of the most frequent postoperative complications worldwide and preventive measures are still an important research topic. High infection rates are not uncommon, especially in visceral surgery. At the same time, frequently not all evidence-based measures are carried out in a standardized manner. The aim of this article is to summarize the relevant literature on evidence-based measures for prevention of SSI. Although evidence-based medicine has already become well-established in surgery, the opinion of experts often still prevails. MATERIAL AND METHODS: The current literature on preventive measures and recommendations was reviewed and the results are appraised. RESULTS: Many different preventive measures could be identified in the literature, which can be classified into preoperative, intraoperative and postoperative measures. Recommendations for implementation of individual measures are made depending on the underlying evidence. CONCLUSION: The occurrence of SSI can effectively be reduced by adhering to evidence-based principles.

[Establishment of the new cross-sectional field of pain medicine : An application example at the medical faculty of Heidelberg]. / Etablierung des neuen Querschnittsbereichs Schmerzmedizin : Ein Anwendungsbeispiel der Medizinischen Fakultät Heidelberg.

Studies from recent years paint a picture of qualitatively deficient treatment in pain medicine. In order to improve the situation knowledge on targeted diagnostics and effective therapy should be imparted at an early stage during undergraduate studies. For this reason the cross-sectional field Q14 - pain medicine was newly created in the revision of the medical physician licencing regulations. The Q14 was then established in a longitudinal, multidisciplinary form at the medical faculty in Heidelberg, whereby the complete Kern cycle was run through. The present project report describes and discusses the establishment. The results of the first multiple choice examination and an online-based evaluation by the students are presented. The latter show that the students recognized the relevance of the teaching program for their future professional career; however, the presentation of the interdisciplinary aspect must still be improved. The students were critical of the longitudinal structure and this does indeed involve a great deal of organization for the faculty and students. On the other hand this corresponds to the basic conception of a cross-sectional field and gives a good depiction of the multidisciplinary character. The first evaluation results set the precedent for further fine adjustments of the cross-sectional field. A continuous further development is generally needed with respect to the Kern cycle.

[Current standards of abdominal wall closure techniques : Conventional suture techniques]. / Aktuelle Studienlage zum Bauchdeckenverschluss : Klassische Nahttechniken.

BACKGROUND: The most frequent complications following midline abdominal laparotomy include incisional hernias, which develop in 10-15 % of patients and surgical site infections in 15-25 % of cases; however, the risk of these complications can be reduced by the surgical technique and the use of special suture materials. In 2010, the INLINE meta-analysis performed by the Study Centre of the German Society of Surgery (SDGC) revealed that a continuous suture technique using slowly absorbable suture material resulted in the lowest risk of developing postoperative incisional hernia after elective midline laparotomy. OBJECTIVE: The aim of this study was to perform a systematic literature search to identify all randomized controlled trials (RCTs) that have been published since 2010 concerning conventional abdominal wall closure in order to update the 2010 INLINE meta-analysis and summarize current evidence. MATERIAL AND METHODS: On 28 January 2016, a systematic literature search was performed in MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL). All RCTs dealing with abdominal wall closure after midline laparotomy were identified and included for further analysis. RESULTS: Since 2010 a total of 9 RCTs comparing different techniques of abdominal wall closure have been published. Three monocentric RCTs comparing different suture materials, showed no significant differences to the INLINE meta-analysis regarding incisional hernia development; therefore, slowly absorbable sutures using a continuous suture technique are still recommended for abdominal wall closure in elective cases. Furthermore, six RCTs were identified which investigated antimicrobial suture materials but failed to show an overall advantage for Triclosan-coated suture material with respect to surgical site infections. CONCLUSION: Current evidence shows that slowly absorbable monofilament suture material using a continuous suture technique provides the best results with regard to incisional hernia rates after elective midline laparotomy. Triclosan-coated sutures cannot be recommended as a standard suture material as they failed to reduce surgical site infections. For emergency laparotomies no evidence exists to recommend a specific kind of suture technique or a special suture material.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

[Benefit assessment of operative interventions from the perspective of surgical research]. / Nutzenbewertung operativer Maßnahmen aus der Perspektive der chirurgischen Forschung.

The benefit assessment of surgical procedures serves as the basis for the concept of evidence-based surgery. However, especially in the field of surgery, many interventions are lacking assessment in high-quality clinical trials. Therefore, a well-structured benefit assessment of surgical interventions in the future is imperative. Considering the different perspectives, e.g. of the patients, surgeons, industry or health care investors, the implications of the benefits and risks of a procedure can differ significantly. Researchers have to abide by different regulations, depending on the type of intervention being evaluated in a surgical trial. Furthermore, the benefit assessment of surgical procedures poses specific challenges, from the choice of a relevant endpoint to issues concerning the standardization of the interventions and the impact of learning curves. The IDEAL concept, which was established by a group of international experts in 2009, serves as a framework for the future development and assessment of innovations in the field of surgery. For example, the SDGC (Study Center of the German Society of Surgery) and CHIR-Net (Surgical Studies Network) indicate that such collaborations of clinicians and methodologists can lead to the creation of a qualified structure for the effective benefit assessment of surgical procedures. In the future, the aforementioned evidence gaps must be eliminated and innovations evaluated efficiently by the work of such networks.

Randomized controlled multicenter trial on the effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound fibrin sealant during liver resection (ESSCALIVER study, NCT00918619).

BACKGROUND: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection. METHODS: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period. RESULTS: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [-6.0 %, 19.8 %] does not include the lower noninferiority margin (-10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups. CONCLUSION: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.

Transferring innovative freehand SPECT to the operating room: first experiences with sentinel lymph node biopsy in malignant melanoma.

PURPOSE: The purpose of this study was to report on the first experiences with freehand single-photon emission-computed tomography (freehand SPECT) in sentinel lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a novel imaging modality combining gamma probes, surgical navigation systems, and emission tomography algorithms, designed to overcome some of the limitations of conventional gamma probes. METHODS: In this study 20 patients with malignant melanoma underwent conventional planar scintigraphy prior to surgery. In the operating room, the number and location of separable SLNs were detected first by a pre-incisional scan with freehand SPECT to render a 3D-image of the target site and afterwards by a scan with a conventional gamma probe. After SLNB another scan was performed to document the removal of all targeted SLNs. RESULTS: Planar scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT mapped 38 of these nodes as well as one additional node in one patient (95.0% node based sensitivity). The results of freehand SPECT were identical to those of planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected as they matched the position of SLNs detected on preoperative planar scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D-image of the radioactive labelled SLNs, facilitating their detection and resection.

Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6.

An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. HI 6. In view of substantial species differences regarding reactivation properties of oximes, the effect of HI 6 was investigated with sarin, tabun and soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 µM HI 6 resulted in an almost complete recovery of sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 µM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 µM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.

Defining new pancreatic tumour entities by molecular analysis.

Recent advances in molecular biology, biochemistry and genetics have broadened our understanding of tumourigenesis and of the maintenance and spread of pancreatic cancer far beyond traditional microscopic histopathological analysis. While the main focus of pancreatic cancer research has been on pancreatic ductal adenocarcinoma, molecular research has also led to a better understanding of rare tumours of the pancreas, as well as to the definition of previously unknown tumour entities that can only be identified through the application of molecular tools. Furthermore, molecular analysis increasingly reveals the genetic and cell biological heterogeneity of established tumour entities, making subclassification of tumours possible. Genetic and molecular approaches may, therefore, not only lead to a better understanding of the pathogenesis of pancreatic tumours, but also culminate in more precise diagnosis as well as individually tailored treatment strategies for affected patients.

Histopathological features of autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas characterised by lymphoplasmacytic infiltrates, interstitial fibrosis, periductal inflammation and periphlebitis. Although first described more than four decades ago, it has not gained widespread attention until the 1990s when new insights into its aetiology, clinical presentation and management were discovered. Although nowadays widely accepted as a form of chronic pancreatitis, recent evidence suggests that AIP might not be confined to the pancreas but rather be an inflammatory pancreaticobiliary disease (autoimmune pancreatocholangitis, AIPC) with possible systemic involvement and association with other autoimmune disorders. This article reviews current concepts of AIP with special focus on the histopathological features of the disease.