Conservative therapy of severe acute pancreatitis is a safe option - results of a 15-year long-term follow-up cohort study.

Treatment of severe acute pancreatitis can be challenging with high mortality. In 2012 we reported a significantly reduced in-hospital mortality if these patients are treated conservatively for at least the first 3 weeks in the course of the disease as compared to early necrosectomy. We performed a long-term follow-up and compared the outcome of these two study groups (group 1 - early necrosectomy, n=20 versus group 2 - primary conservative treatment, n=24). Materials and methods: Follow-up of the study patients by personal contact, phone survey, or data from primary care physician. Median follow-up was 15 years (range 10-22 years). This trial is registered at: Research Registry UIN researchregistry8697. Results: Eleven survivors of group 1 and 22 survivors of group 2 were discharged after initial treatment. Ten of 11 surviving patients of group 1 (90.9%) and 20 of 22 surviving patients of group 2 (90.9%) were included in this study. Between groups, there were no statistical differences in the rate of resubmission (P=0.23), development of diabetes (P=0.78), or development of exocrine insufficiency (P=1.0). However, long-term survival in group 2 was significantly better than that of group 1 (P=0.049). Conclusion: Primary conservative treatment of severe acute pancreatitis without early necrosectomy does not lead to early complications and even shows an advantage in long-term survival. Therefore conservative treatment of severe acute pancreatitis is safe and there is no absolute need for necrosectomy in severe acute pancreatitis.

Acute Mesenteric Ischemia.

BACKGROUND: Despite constant improvements in diagnostic as well as interventional and surgical techniques, acute mesenteric ischemia (AMI) remains a life-threatening emergency with high mortality rates. The time to diagnosis of AMI is the most important predictor of patients' outcome; therefore, prompt diagnosis and intervention are essential to reduce mortality in patients with AMI. The present review was performed to analyze potential risk factors and to help find ways to improve the outcome of patients with AMI. SUMMARY: Whereas AMI only applies to approximately 1% of all patients with an "acute abdomen," its incidence is rising up to 10% in patients >70 years of age. The initial clinical stage of AMI is characterized by a sudden onset of strong abdominal pain followed by a painless interval. Depending on the extent of disease, the symptoms of nonocclusive mesenteric ischemia (NOMI) and patients with a venous thrombosis can be very different from those of acute occlusive ischemia. Biphasic contrast-enhanced CT represents the gold standard for the diagnosis of arterial and venous occlusion. In case of a central occlusion of the superior mesenteric artery or signs of peritonitis, immediate surgery should be performed. If major bowel resection becomes necessary, critical residual intestinal length limits must be kept in mind. Endovascular techniques for arterial occlusion have taken on a much greater importance today. For stable patients with NOMI, interventional catheter angiography is recommended because it enables diagnosis and treatment with selective application of vasodilators. Depending on its degree, interventional treatment with a transhepatic catheter lysis should be considered for acute and chronic portal vein thrombosis. KEY MESSAGE: The prompt and targeted use of the appropriate diagnostics and interventions appears to be the only way to reduce the persistently high mortality rates for AMI.

Comparison Between Endoscopic Vacuum Therapy and Conventional Treatment for Leakage After Rectal Resection.

BACKGROUND: Anastomotic leakage after rectal resection represents a severe complication for the patient and requires an early and appropriate management. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in several institutions in Germany, and commercially available systems are currently distributed in approximately 30 countries worldwide. However, there is no evidence that EVT is superior to any other treatment for anastomotic leakage after rectal resection. METHODS: Twenty-one patients treated with EVT for anastomotic leakage after rectal resection were retrospectively compared to a historical cohort of 41 patients that received conventional treatment. Primary endpoints were death, treatment success and long-term preservation of intestinal continuity. Secondary endpoints were length of hospital stay and duration of treatment. RESULTS: There was no difference in mortality (p = 0.624). The intention-to-treat analysis showed a significantly higher success rate of EVT compared to conventional treatment (95.2% vs. 65.9%, p = 0.011). EVT was associated with preservation of intestinal continuity in a significant higher percentage of patients than patients undergoing conventional treatment (86.7% vs. 37.5%, p = 0.001). Conventional treatment tended to a shorter length of hospital stay (31.1 vs. 42.2 days, p = 0.066) but with no difference in overall duration of treatment. Time until closing of a diverting stoma did not differ between groups (10.2 months in the EVT group vs. 9.4 months in the conventional treatment group, p = 0.721). CONCLUSION: According to this retrospective study, conventional therapy and EVT are both options for the treatment of anastomotic leakage after rectal resection. EVT might be more effective in terms of definite healing and preservation of intestinal continuity.

The Water-Holding Procedure for Ensuring Postoperative Continence Prior Restoring Intestinal Continuity.

BACKGROUND: A defunctioning stoma can become necessary in a relevant number of patients undergoing gastrointestinal surgery. As a matter of course, patients seek an early closure of the stoma. However, preoperative management of these patients varies and the prediction of continence after stoma removal can become challenging. Patients might be fully continent despite low manometric pressures and vice versa. An easy and reliable way to predict continence after stoma reversal would improve patients' management and outcome. Although frequently performed in various surgical centers in Germany, there is no published data on the water-holding test. Hence, this is the first study evaluating the role of the test in clinical practice. METHOD: We performed a prospective pilot study to evaluate the role of anorectal manometry and the water-holding procedure as a predictor of postoperative continence prior to stoma reversal. Inclusion criteria were a successfully passed water-holding test, any type of fecal diversion and the possibility of restoring intestinal continuity. Preoperative low manometric pressure levels were not an exclusion criteria for stoma reversal. Fifty-two patients with ostomy were consecutively enrolled in this study between October 2013 and February 2016. Anorectal manometry was performed in all patients prior to stoma reversal. After stoma removal, patients were followed-up for 6 months. Postoperative incontinence was determined using the Wexner incontinence score. RESULTS: A total of 52 patients (38 males, 14 females) were included at an average age of 59 (range 33-83) years. Most frequent indications for intestinal diversion were rectal cancer surgery, IBD-related surgery, or surgery for diverticular disease. Low anterior rectal resection was performed in 17 patients (32.7%), followed by a proctocolectomy in 9 (17.3%), colectomy in 9 (17.3%), and recto-sigmoid resection in 7 patients (13.5%). Median time from stoma creation to reversal was 206 days (range 48-871 days). All patients had successfully passed the standardized water-holding test. At the same time, the majority of patients had low preoperative manometric pressure values and would normally not have been reversed at that point. The median postoperative Wexner incontinence score was at 1.5 (range 0-20), 0.5 (range 0-14), and 0 (range 0-11) at 14, 60, and 180 days after stoma reversal. Low preoperative manometric squeeze and/or resting pressure levels were not associated with a higher postoperative incontinence score at 14, 60, or 180 days after stoma reversal. CONCLUSION: A standardized water-holding test can function as an easy and reliable method before stoma reversal to predict sufficient postoperative fecal continence. In case of a sufficient water-holding test despite low manometric pressure levels, the risk for postoperative anal incontinence seems to be low. Preoperative manometric pressure levels do not appear to predict postoperative continence.

No need for surgery? Patterns and outcomes of blunt abdominal trauma.

INTRODUCTION: The management of a patient suffering from blunt abdominal trauma (BAT) remains a challenge for the emergency physician. Within the last few years, the standard therapy for hemodynamically stable patients with BAT has transitioned to a non-operative approach. The purpose of this study is to evaluate the outcome of patients with BAT and to determine the reasons for failure of non-operative management (NOM). MATERIALS AND METHODS: Analysis of 176 consecutive patients treated for BAT was conducted in a German level 1 trauma center from 2004 to 2011. Abdominal injuries were classified according to the American Association for the Surgery of Trauma (AAST). Patients included were demonstrated to have objective abdominal trauma with either free fluid on focused assessment with sonography for trauma (FAST) or computed tomography (CT), or proven organ injury. RESULTS: Patients, 142 of 176 (80.7%), with BAT were initially managed non-operatively, with a success rate of 90%. The rates of NOM success were higher among those with less severe injuries; 100% with Abbreviated Injury Scale (AIS) of 1. In total, 125 patients (71.0%) were managed non-operatively, and 51 (29.0%) required surgical intervention. NOM failure occurred in 9.2% of the patients, the most common reason being initially undiagnosed intestinal perforation (46.2%). Positive correlation was identified (r = 0.512; p < 0.001) between the ISS (injury severity score) and the NACA (National Advisory Committee of Aeronautics) score. The delay in operation in NOM failure was 6 h in patients with underlying hepatic or splenic rupture and 34 h with intestinal perforation. The overall mortality of 5.1% was attributed especially to old age (p = 0.016), high severity of injury (p < 0.001), and greater need for blood transfusion (p < 0.001). CONCLUSION: NOM was successful for the vast majority of blunt abdominal trauma patients, especially those with less severe injuries. NOM failure and operative delay were most commonly due to occult hollow viscus injury (HVI), the detection of which was achieved by close clinical observation and abdominal ultrasound in conjunction with monitoring for rising markers of infection and by multidetector computed tomography (MDCT) if additionally indicated. Based on this concept, the delay in operation in patients with NOM failure was short. This study underscores the feasibility and benefit of NOM in BAT.

Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research.

Over the time period from 2006 to 2017, consecutive patients operated on at the University Medical Center Rostock participated in the comprehensive biobanking and tumor-modelling approach known as the HROC collection. Samples were collected using strict standard operating procedures including blood (serum and lymphocytes), tumor tissue (vital and snap frozen), and adjacent normal epithelium. Patient and tumor data including classification, molecular type, clinical outcome, and results of the model establishment are the essential pillars. Overall, 149 patient-derived xenografts with 34 primary and 35 secondary cell lines were successfully established and encompass all colorectal carcinoma anatomic sites, grading and staging types, and molecular classes. The HROC collection represents one of the largest model assortments from consecutive clinical colorectal carcinoma (CRC) cases worldwide. Statistical analysis identified a variety of clinicopathological and molecular factors associated with model success in univariate analysis. Several of them not identified before include localization, mutational status of K-Ras and B-Raf, MSI-status, and grading and staging parameters. In a multivariate analysis model, success solely correlated positively with the nodal status N1 and mutations in the genes K-Ras and B-Raf. These results imply that generating CRC tumor models on the individual patient level is worth considering especially for advanced tumor cases with a dismal prognosis.

Neoadjuvant radio-chemotherapy prolongs healing of anastomotic leakage after rectal resection treated with endoscopic vacuum therapy.

BACKGROUND: Neoadjuvant radiochemotherapy (nRCT) is an important component in the treatment of advanced rectal cancer. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in many institutions in Germany. Published case series report on average success and stoma reversal rates of more than 80%. However, so far, there is no distinct report on the potential influence of nRCT on EVT. METHODS: A total of 11 patients treated with EVT for anastomotic leakage after nRCT and rectal resection were retrospectively compared with a cohort of eight patients with rectal anastomotic leakage without neoadjuvant treatment. Primary endpoints were death, treatment success, and long-term preservation of intestinal continuity. Secondary endpoint was the duration of treatment. Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 23.0. RESULTS: There was no difference in mortality (0%), success rate (90.9% versus 100%, p = 0.381), or long-term preservation of continuity (63.6% versus 62.5%, p = 0.960). After nRCT, patients showed a significant longer duration of EVT (31.1 days versus 15.9 days, p = 0.040) which was associated with a significantly higher number of sponge applications (9.6 versus 5.0, p = 0.042). CONCLUSIONS: In our analysis, EVT showed success in over 90% of patients with anastomotic leakage after rectal resection for colorectal cancer, regardless of neoadjuvant treatment. However, in case of anastomotic leakage, nRCT seems to be associated with the need for a significant longer duration of EVT.

Evaluation of peripheral artery disease with the TIVITA® Tissue hyperspectral imaging camera system.

BACKGROUND: Objective, reliable and easy screening for peripheral artery disease (PAD) is essential to confirm the diagnosis and initiate the respective treatment. Therefore, a new non-invasive hyperspectral camera (TIVITA® Tissue) was tested in patients with and without PAD. OBJECTIVE: It was hypothesized that the oxygenation parameters of the TIVITA® Tissue correlate to established modalities for detection of PAD and allow differentiation between individuals with and without PAD. METHODS: Evaluation of tissue oxygenation was performed in the angiosome of the medial plantar artery in 25 healthy young people and in 24 patients with and 25 patients without PAD in comparable age. Thereby, superficial oxygenation (StO2) and near-infrared (NIR) perfusion index were measured with the TIVITA® Tissue. Additionally, the ankle-brachial-index (ABI), the complaint free walking distance and the vascular quality of life were assessed and demographic data were obtained from all participants. RESULTS: TIVITA® Tissue analysis revealed significantly reduced StO2 and NIR perfusion index in PAD compared to healthy young participants and patients without PAD. StO2 and NIR perfusion index positively correlated with ABI, the complaint free walking distance and the vascular quality of life score. CONCLUSIONS: In summary, this new hyperspectral imaging camera bears great potential for PAD screening as well as for follow up.

Targeting Immune-Related Molecules in Cancer Therapy: A Comprehensive In Vitro Analysis on Patient-Derived Tumor Models.

This study investigated the impact of immune-related pathway inhibition, among them indolamine 2,3-dioxygenase (IDO), alone and together with immune cells on growth and viability of colorectal cancer (CRC) cells. A panel of patient-derived CRC cell lines with different molecular characteristics (CpG island methylator phenotype, chromosomal, and microsatellite instability) was included. Initial phenotyping of CRC cell lines (n=17) revealed high abundance of immunosuppressive checkpoint-molecules in general, but an individual profile for IDO. Presence of immune-related molecules was independent of the molecular subtype. Selective treatment of CRC cell lines showing high or low IDO expression (n=2 cell lines each) was performed with single agents and combinations of Indoximod, Curcumin, and Gemcitabine with and without the addition of peripheral blood lymphocytes (PBL) in an allogeneic setting. All substances affected CRC cell growth in a cell line specific manner. The combination of Curcumin and Gemcitabine proved to be most effective in tumor cell elimination. Functional read-out analyses identified cellular senescence, after both single and combined treatment. Curcumin alone exerted strong cytotoxic effects by inducing early and late apoptosis. Necrosis was not detectable at all. Addition of lymphocytes generally boosted antitumoral effects of all IDO-inhibitors, with up to 80 % cytotoxicity for the Curcumin treatment. Here, no obvious differences became apparent between individual cell lines. Combined application of Curcumin and low-dose chemotherapy is a promising strategy to kill tumor target cells and to stimulate antitumoral immune responses.

Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines.

AIM: To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens. METHODS: Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radio- and chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18F-fluorodeoxyglucose (FDG) and proliferation with 18F-fluorothymidine. RESULTS: We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines (HROC126, HROC284Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/ non-MSI-H (sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APCwt , TP53wt , KRASwt , BRAFwt , PTENwt ; HROC239 T0 M1: APCmut , P53wt , KRASmut , BRAFwt , PTENmut and HROC284Met: APCwt , P53mut , KRASmut , BRAFwt , PTENmut . All cell lines could be characterized as epithelial (EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION: These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer.

[Medical Device Regulation as current challenge for the legally safe introduction of new technologies]. / Medical Device Regulation als aktuelle Herausforderung für die rechtssichere Einführung neuer Technologien.

The main goal of the Medical Device Regulation (MDR) is the improvement of patient safety by laying down rules concerning the approval of medical devices for human use in the European Union. The MDR contains an extension of the conformity assessment procedure for products in the higher risk categories IIb and III. The clinical testing and assessment are regulated more strictly by e.g. the scrutiny process conducted by expert panels following the technical certification. The demand for documentation is vastly increasing due to more detailed registration (UDI) and an extension of post-market surveillance. The German Society of Surgery (DGCH) and the German Society for Biomedical Engineering have already defined a staged concept for innovation testing and clinical assessment during finalization of the MDR that contains the highest level of patient safety while simultaneously maintaining the potential for innovation. Essential elements are present in the MDR and can be implemented in a targeted way. The 3­year phase of national MDR-implementation must be used for a proactive adaptation. The DGCH is represented in the advisory council of the Federal Ministry of Health (BMG) by the Association of the Scientific Medical Societies in Germany (AWMF). The aim is a responsible harmonization of national structures with the regulations of the MDR by the construction of specific registries which should be the responsibility of medical societies. The early integration of health technology assessment will be of importance during the planning phase of product development to facilitate a positive decision on reimbursement.

Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line.

AIM: To establish cell line and patient-derived xenograft (PDX) models for neuroendocrine carcinomas (NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research including biomarker testing and drug response prediction. METHODS: Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue (HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting (i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid cancers. RESULTS: The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a CpG island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS (wt), BRAF (mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION: We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC.

The Ongoing Challenge of Acute Mesenteric Ischemia.

BACKGROUND: The lethality of acute mesenteric ischemia (AMI) remains quite high with 50-70%. The main reasons for that are the fact that AMI is rarely taken into consideration by the differential diagnosis of acute abdomen, the time-consuming diagnostic process, and the lack of a standardized therapeutic concept. The present interdisciplinary review aims to increase awareness among physicians and to help improve clinical outcomes. METHODS: This clinical therapeutic review is based on author expertise as well as a selective literature survey in PubMed based on the term 'mesenteric ischemia', combined with the terms 'arterial', 'clinical presentation', 'diagnosis', 'therapy', 'surgery', and 'interventional radiology'. Based on these search results as well as on the guidelines of the German Society of Vascular Surgery, the American College of Cardiology, and the American Heart Association, we present an interdisciplinary treatment concept. RESULTS: AMI is a vascular emergency that can be successfully treated only within the first hours after the onset of symptoms. Computed tomography angiography is the diagnostic method of choice. Intensive care unit treatment can prevent the occurrence of multiple organ failure. Treatment primarily consists of the revascularization of the mesenteric arteries. Endovascular techniques should be given priority, whereas signs of peritonitis or a central arterial occlusion with high thrombus load primarily require a surgical approach in order to save time and increase patient safety. Additional bowel resections can play a significant role in the treatment of intestinal sepsis. CONCLUSION: Prompt and goal-oriented diagnosis and consistent treatment of AMI within 4-6 h from the onset of symptoms can be decisive for the reduction of AMI-associated lethality. In order for this to happen, a standardized concept of emergency treatment needs to be implemented.

[Risk Factors for Early Surgery and Surgical Complications in Crohn's Disease]. / Risikofaktoren für einen frühen OP-Zeitpunkt und chirurgische Komplikationen bei Morbus Crohn.

BACKGROUND: In recent decades, developments in drug therapy have significantly postponed the need for surgery. Nevertheless, the majority of patients with Crohn's disease still require one or more surgical interventions during the course of their disease. An analysis of epidemiological data as well as the surgical results of our own patients should help to identify risk factors for early surgery, re-operations and perioperative complications. METHODS: A retrospective analysis including 120 consecutive patients with Crohn's disease and needing surgical intervention was carried out at the University Hospital of Rostock (UMR), Germany. Statistical analysis was performed using SPSS. RESULTS: A total of 284 operations were recorded in 120 patients, of which 207 were performed on the UMR. The mean age at first surgery was 38 years (range: 17 - 66); initial diagnosis of Crohn's was on average at the age of 30 (range: 9 - 62). Each patient was operated 2 - 3 times during the course of their disease (range 1 - 9). Patients older than 30 years had significantly shorter time interval to the first operation. The number of operations per patient was significantly influenced by the localisation and behaviour of the disease. Penetrative behavior was associated with more frequent operations and terminal ileum involvement (L1) with significantly less frequent operations. Risk factors for complication of at least grade III according to Clavien-Dindo included greater age at surgery and at first diagnosis, decreased albumin levels and increased CRP. Anastomotic leakages were also associated with these risk factors as well as preoperative intake of > 20 mg prednisolone equivalent per day or cumulative dosage of 280 mg over the last 14 days prior to surgery. Anastomosis configuration and microscopic involvement of the resection margins had no statistically significant influence on the development of anastomotic leakage. CONCLUSION: Diagnosis after the age of 30 was associated with a significantly earlier need for surgery in this analysis. Patients with terminal ileum involvement (L1) had a significantly lower surgical frequency than patients with colon or combined Crohn's disease. Age, albumin, CRP and a steroid medication > 20 mg per day were predictors for perioperative complications.

High compliance with guideline recommendations but low completion rates of adjuvant chemotherapy in resected pancreatic cancer: A cohort study.

BACKGROUND: Adjuvant chemotherapy (adCx) is an integral part of multimodal treatment in resected pancreatic ductal adenocarcinoma (PDAC) and is recommended by the German S3 guideline since 2007 in all patients. We aimed to investigate the impact of this guideline at our institution. METHODS: In 151 of 403 pancreatic resections performed histopathology revealed PDAC. Follow-up data were available from 143 patients (95%) representing our study group. The rate of recommended, initiated and fully completed adCx was analyzed for period 1 (09/2003-07/2007) and period 2 (08/2007-08/2014). RESULTS: Our study group comprised 49 patients in period 1 and 94 patients in period 2. AdCx was recommended, initiated and completed in 42/49 (86%), 34/49 (69%) and 22/49 (45%) patients in period 1 and in 93/94 (99%), 78/94 (83%) and 49/94 (52%) patients in period 2, respectively. Only the increase in recommendations for adCx was statistically significant (p = 0.0024). Overall, only 50% (71/143) of patients fully completed the Cx protocol. Completed adCx resulted in a significantly longer (p = 0.0225) overall survival compared to patients with incomplete or without adCx. Multiple logistic regression revealed adCx (p = 0.0046) as independent factor of survival. The hazard ratio for fully completed adCx was 0.406 and for incomplete adCx 0.567. CONCLUSION: Our results indicate a high acceptance of the S3-guidline recommendation for adCx in resected PDAC in a routine setting, which, however, is completed in only 50% of all patients. Fully completed adCx had the most powerful effect on improving overall survival.

Before and after Anorectal Surgery: Which Information Is Needed from the Functional Laboratory?

BACKGROUND: Anorectal surgery covers a wide spectrum of surgery. Diagnostic workup of anorectal disease is based on clinical examination with basic functional tests followed by more elaborate diagnostic tests. Since the incidence of anorectal disorders increases with age, more patients will present in outpatient clinics, thus underlining the relevance of this topic. METHODS: A PubMed literature search was performed using the terms 'anal incontinence', 'anal and rectal surgery', 'functional diagnostics', and combinations of these terms. No restriction regarding publication year or publication type was applied but randomized trials, 'metanalyses', or guidelines were ranked higher. Only articles in English or German were included. RESULTS: The diagnostic value of digital rectal examination, anal manometry and endosonography, the water holding procedure, contrast enema, and incontinence scores is summarized. CONCLUSION: The article focusses on basic clinical and functional diagnostic tests which can be easily applied in the pre- and postoperative setting to evaluate the postoperative outcome.

Murine Endogenous Retroviruses Are Detectable in Patient-Derived Xenografts but Not in Patient-Individual Cell Lines of Human Colorectal Cancer.

Endogenous retroviruses are remnants of retroviral infections. In contrast to their human counterparts, murine endogenous retroviruses (mERV) still can synthesize infectious particles and retrotranspose. Xenotransplanted human cells have occasionally been described to be mERV infected. With genetic engineered mice and patient-derived xenografts (PDXs) on the rise as eminent research tools, we here systematically investigated, if different tumor models harbor mERV infections. Relevant mERV candidates were first preselected by next generation sequencing (NGS) analysis of spontaneous lymphomas triggered by colorectal cancer (CRC) PDX tissue. Two primer systems were designed for each of these candidates (AblMLV, EcoMLV, EndoPP, MLV, and preXMRV) and implemented in an quantitative real-time (RT-qPCR) screen using murine tissues (n = 11), PDX-tissues (n = 22), PDX-derived cell lines (n = 13), and patient-derived tumor cell lines (n = 14). The expression levels of mERV varied largely both in the PDX samples and in the mouse tissues. No mERV signal was, however, obtained from cDNA or genomic DNA of CRC cell lines. Expression of EcoMLV was higher in PDX than in murine tissues; for EndoPP it was the opposite. These two were thus further investigated in 40 additional PDX. In addition, four patient-derived cell lines free of any mERV expression were subcutaneously injected into immunodeficient mice. Outgrowing cell-derived xenografts barely expressed EndoPP. In contrast, the expression of EcoMLV was even higher than in surrounding mouse tissues. This expression gradually vanished within few passages of re-cultivated cells. In summary, these results strongly imply that: (i) PDX and murine tissues in general are likely to be contaminated by mERV, (ii) mERV are expressed transiently and at low level in fresh PDX-derived cell cultures, and (iii) mERV integration into the genome of human cells is unlikely or at least a very rare event. Thus, mERVs are stowaways present in murine cells, in PDX tissues and early thereof-derived cell cultures. We conclude that further analysis is needed concerning their impact on results obtained from studies performed with PDX but also with murine tumor models.

Can Recognition of Spinal Ischemia Be Improved? Application of Motor-Evoked Potentials, Serum Markers, and Breath Gas Analysis in an Acutely Instrumented Pig Model.

BACKGROUND: Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. METHODS: In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, clinical and neurological status was evaluated (Tarlov score). Spinal cord histology was obtained in postmortem. RESULTS: Permanent vessel ligature induced a worse neurological outcome and a higher number of necrotic motor neurons compared to clamping. Changes of serum markers remained unspecific. After laparotomy, exhaled acetone and isopropanol showed highest concentrations, and pentane and hexane increased during ischemia-reperfusion injury. CONCLUSIONS: To mimic spinal ischemia occurring in humans during aortic aneurysm repair, animal models have to be meticulously evaluated concerning vascular anatomy and function. Volatiles from breath indicated metabolic stress during surgery and oxidative damage through ischemia reperfusion. Breath VOCs may provide complimentary information to conventional monitoring methods.

[Register of Difficult Surgical Situations]. / Register der schwierigen chirurgischen Situationen.

Every surgical problem that increases the likelihood of intraoperative and postoperative complications is considered to be a difficult surgical situation. Based on this definition, Korenkov et al. proposed to classify patients according to the following intraoperative difficulty levels (I to IV): (I) ideal situation (easy to operate, no problems), (II) fairly easy/manageable/simple (some minor difficulties may occur), (III) difficult/problematic (difficult to operate; some operative techniques are considerably more difficult than others), and (IV) very difficult (every operative step is difficult/challenging). Kaafrani et al. proposed a severity classification for intraoperative adverse events. Depending on the severity level, classes range from I (injury requiring no repair) to VI (intraoperative death). Clavien and colleagues published a globally established classification system for postoperative complications. In this classification, the severity of postoperative complications ranges from severity grade I (minimal deviation from the normal postoperative course) to severity grade V (death of patient). Based on the proposed classifications and the problems of individual surgical decision-making, we had the idea to create a Register of Difficult Intraoperative Situations (DIS register). The basic principle of such a register is the collection of an individual expert's experiences. The scientific analysis should focus on patients with apparent modifications in treatment due to difficult intraoperative situations. Registration and processing of enrolled cases will be performed anonymously based on an appropriate IT platform. The main goal of this register is to develop an accessible database for practising surgeons. This will provide an opportunity for every surgeon to find out what other surgeons did in similar situations.