[Robotic Rectal Cancer Surgery]. / Roboterassistierte Rektumkarzinomchirurgie.

BACKGROUND: The oncological outcome of patients with rectal cancer has improved considerably over the past few decades. This is mainly due to the introduction of the surgical concept of total mesorectal excision (TME) and the implementation of multimodal treatment strategies. Additionally, it has recently been demonstrated that the oncological results of open and laparoscopic TME are comparable. For some time there has been an ongoing debate on the potential relevance of robotic assistance systems in visceral surgery. The aim of this study was to evaluate the operative and perioperative outcomes of patients with rectal or rectosigmoid cancer, who were operated on using the Da Vinci Surgical System. PATIENTS AND RESULTS: We retrospectively analysed the outcomes of 202 consecutive patients, who were operated between September 2010 and November 2015 in three Surgical Centers. The cohort consisted of 136 men and 66 women with a mean BMI of 28. We performed the following procedures: 49 anterior rectal resections, 119 low anterior rectal resections, and 34 abdominoperineal excisions. Conversion to an open procedure was required in 13 patients. Non-surgical complications (n = 27) occurred in 24 patients (12%) and surgical complications (n = 67) in 62 patients (31%). Most complications were due to abdominal or sacral wound infections (n = 25) and anastomotic leaks (n = 18). The mortality rate within 30 days was 2%. The rate of R0 resections was 95%, with circumferential resection margins being negative in 98% of the patients. The quality of the mesorectal resection was scored as good in 91% of the patients. CONCLUSIONS: The Da Vinci Surgical System can be used safely and with a low complication rate for surgical treatment of rectal cancer. While primary evidence suggests that the outcome of robotic-assisted surgery is comparable with open and laparoscopic surgery, its definitive value has to be determined upon publication of the prospective randomized ROLARR trial. The main advantages of the Da Vinci system are its endowristed instruments with multiple degrees of freedom and its optimised visualisation (3D, stable camera platform controlled by the surgeon). Another positive feature is the significant ergonomic advantage for the surgeon.

Preliminary results of the global audit of treatment of refractory status epilepticus.

The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus".

A neuroradiologist's guide to arterial spin labeling MRI in clinical practice.

Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood-brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies.

[General principles of tumour biology in visceral surgery]. / Allgemeine Grundlagen der Tumorbiologie in der Viszeralchirurgie.

Within the last decade, there has been a tremendous progress in understanding the molecular basis of cancer. In particular, the development and the characteristic features of cancer cells are being increasingly understood. The understanding of these molecular characteristics is mandatory for the development of novel, targeted therapeutic strategies and their integration into clinical practice. In addition, tumour genetics play a critically important role for hereditary cancer syndromes, with respect to both diagnostics and clinical decision-making. The aim of this review is to highlight general principles of tumour genetics from a visceral surgeon's point of view, although a comprehensive summary of all aspects would be beyond the scope of this article due to the complexity of the topic.

Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

[Value of one-stage surgical treatment of diffuse peritonitis (relaparotomy on demand): a single-center analysis]. / Stellenwert der einzeitigen chirurgischen Therapie bei diffuser Peritonitis (Relaparotomie "on demand"): eine unizentrische Analyse.

BACKGROUND: Despite modern surgical and intensive-care concepts, diffuse peritonitis remains a major source of high morbidity and mortality. The aim of this study was to critically evaluate the value of relaparotomy on demand (ROD) for patients with diffuse peritonitis. PATIENTS AND RESULTS: In a retrospective analysis, the clinical course of 231 patients with diffuse peritonitis was analysed. The mean Mannheim Peritonitis Index (MPI) was 25.3. Overall lethality in this cohort was 14.3 %. In 214 patients, source control was successful during the index operation, and these patients were treated according to an on-demand strategy. For 178 of these patients, there was no demand for a relaparotomy, whereas 36 of these patients required further surgical interventions. Lethality for these subgroups was 9 % (no relaparotomy) and 27 % (relaparotomy), respectively. CONCLUSIONS: This retrospective analysis confirms that an on-demand strategy is reasonable and feasible after successful source control and lavage. However, it still remains of clinical importance to identify parameters that may assist in selecting those patients who require a relaparotomy.

[Intraoperative fluorescence-guided perfusion assessment using indocyanine green-Increased safety in gastrointestinal anastomoses?] / Intraoperative fluoreszenzgestützte Perfusionsmessung mit Indocyaningrün ­ erhöhte Sicherheit bei gastrointestinalen Anastomosen?

Insufficiency of gastrointestinal anastomoses represents a relevant risk of morbidity and mortality for affected patients. The perfusion quality of the ends of the intestine is the decisive parameter for ensuring sufficient healing of an anastomosis. Intraoperative fluorescence-guided perfusion assessment with indocyanine green is increasingly being used in modern visceral surgery to evaluate tissue perfusion prior to the fashioning of gastrointestinal anastomoses. This technique provides the possibility to distinguish between adequately and inadequately perfused tissue in order to place the anastomosis in the region with the best possible perfusion. Thus, surgeons have a measuring instrument that enables an objective assessment of the perfusion quality of the tissue to be undertaken in addition to a purely subjective macroscopic visual assessment, in order to achieve a better functional result for the patients. Currently, however, the value of this technique has not yet been conclusively clarified. The aim of this review article is to characterize the benefits of intraoperative fluorescence-guided perfusion assessment and to classify it with respect to its significance for routine clinical practice.

The mesopancreas is the primary site for R1 resection in pancreatic head cancer: relevance for clinical trials.

PURPOSE: The prognosis of patients with pancreatic cancer remains poor, even after potentially curative R0 resection. This discrepancy may be due to the histopathological misclassification of R1 cases as curative resections (R0) in the past. MATERIALS AND METHODS: To test this hypothesis, color coding of all resection margins and organ surfaces as part of a standardized histopathological workup was implemented and prospectively tested on 100 pancreatic head specimens. RESULTS: Thirty-five patients were excluded from the analysis owing to the pathohistological diagnosis; only pancreatic ductal adenocarcinoma, distal bile duct adenocarcinoma, and periampullary adenocarcinoma were included. Applying the International Union Against Cancer criteria, 32 cancer resections were classified R0 (49.2%), while 33 cases turned out to be R1 resections (50.8%). The mesopancreas was infiltrated in 22 of the 33 R1 resection specimens (66.6%). It proved to be the only site of tumor infiltration in 17 specimens (51.5%). Applying the Royal College of Pathologists' criteria, 46 resections were classified R1 (70.8%). As expected, the mesopancreas again was the most frequent site of noncurative resection (n = 27; 58.7%). CONCLUSION: Using the intensified histopathological workup for pancreatic head cancer specimens resulted in an increased rate of R1 resections and the mesopancreas represents the primary site for positive resection margins. Such results are of relevance for patients' stratification in clinical trials.

[Evidence-based surgery of rectal cancer]. / Evidenzbasierte Chirurgie des Rektumkarzinoms.

Over the past four decades, the treatment algorithms for rectal cancer have fundamentally changed, which resulted in a considerable improvement of oncological outcomes. In this context, the surgical concept of total mesorectal excision and the implementation of multimodal treatment strategies represent key milestones. These improvements were complemented by a standardized histopathological work-up of the surgical specimen and the introduction of high-resolution magnetic resonance imaging (MRI) diagnostics. In addition, novel surgical techniques have been introduced, such as laparoscopic and robotic rectal resection. Other technological innovations include intraoperative pelvic neuromonitoring and fluorescence imaging. This review highlights the current evidence for selected, sometimes controversially discussed principles of surgical treatment strategies in rectal cancer.

[Intraoperative multidimensional visualization]. / Intraoperative mehrdimensionale Visualisierung.

Modern intraoperative techniques of visualization are increasingly being applied in general and visceral surgery. The combination of diverse techniques provides the possibility of multidimensional intraoperative visualization of specific anatomical structures. Thus, it is possible to differentiate between normal tissue and tumor tissue and therefore exactly define tumor margins. The aim of intraoperative visualization of tissue that is to be resected and tissue that should be spared is to lead to a rational balance between oncological and functional results. Moreover, these techniques help to analyze the physiology and integrity of tissues. Using these methods surgeons are able to analyze tissue perfusion and oxygenation. However, to date it is not clear to what extent these imaging techniques are relevant in the clinical routine. The present manuscript reviews the relevant modern visualization techniques focusing on intraoperative computed tomography and magnetic resonance imaging as well as augmented reality, fluorescence imaging and optoacoustic imaging.

Trends of accuracy of clinical diagnoses of the basic cause of death in a university hospital.

AIMS: To determine the agreement between clinical and necropsy diagnoses of the basic cause of death, and to compare the results with those obtained in a previous study carried out at the same university hospital. METHODS: In total, 4828 necropsies, performed between 1990 and 1995 in the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, were reviewed. Examinations were concluded at the macroscopic part of the necropsy in nearly 35% of the cases. Statistical analysis was carried out using the kappa coefficient comparing the clinical diagnosis and the diagnosis obtained after necropsy. The jackknife method was used to identify comparable kappa values for the comparison of the two periods. RESULTS: Compared with the 1978-80 period, a significant increase in diagnostic agreement was seen for the group submitted to complete necropsy, whereas no similar increase was detected when only the macroscopic step was analysed. CONCLUSIONS: There was a discrete tendency to an improved correlation between clinical and postmortem data stated by full necropsy analysis. The findings show that microscopic analysis remains important to confirm the cause of death in many cases. Diagnostic discrepancies remained high, and therefore complete necropsy continues to be an essential instrument for the assessment of clinical diagnosis.

Measuring medical and nursing students' attitudes toward AIDS.

Investigated attitudes toward AIDS patients among medical and nursing students. Two separate cohorts of students (total N = 550) were surveyed to examine and then validate with confirmatory factor analysis the latent factor structure of such attitudes. Results indicate that a three-factor structure representing fear of contagion, negative emotions, and professional resistance provides a good fit to the data (goodness-of-fit index [GFI] = .92, parsimonious GFI = .67). We offer the resulting 15-item AIDS Attitudes Scale (AAS) as a reliable and valid measure for assessing health care students' attitudes toward working with AIDS patients. Our results suggest the presence of multiple predictors of such attitudes.

Predictors of medical and nursing students' levels of HIV-AIDS knowledge and their resistance to working with AIDS patients.

Among health professionals, knowledge about the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is often limited, inaccurate, or both. Many health professionals also resist working with AIDS patients. This 1988 survey examined exaggerated risk estimates for HIV contagion in relationship to HIV-AIDS knowledge and resistance to working with AIDS patients among medical and nursing students at a large Northwestern teaching hospital. The results indicate that among the respondents, exaggerated risk estimates were associated both with a lack of HIV-AIDS knowledge and with greater resistance to working with AIDS patients. Results from multiple regression analyses revealed that (1) a lack of clinical experience with AIDS patients and (2) antihomosexual attitudes were significantly associated with the students' lack of HIV-AIDS knowledge, even after controlling for the effects of exaggerated risk estimates. The first two variables also were shown to be significantly predictive of the students' resistance to working with AIDS patients, as was an intolerance of drug use and drug users, beyond the influence of exaggerated risk estimates. Specific approaches of developing effective HIV-AIDS educational programs for health professionals are proposed.

Occupational and personal risk estimates for HIV contagion among incoming graduate nursing students.

In an effort to measure both fear of HIV/AIDS contagion and possible co-factors, two cohorts (n = 331) of incoming graduate level nursing students were surveyed during two consecutive academic years. All completed a Risk Perception Scale and an AIDS Attitude Scale; additionally, 118 completed an AIDS Knowledge Scale. Findings indicate this population had tremendous fears of the possibility of HIV infection. Estimates of potential contagion far outweighed scientific estimates of risk, and in some cases corresponded to behaviors that are scientifically purported to have no risk. Of interest in this same regard were perceptions of increased risk in the case of visible testimony to disease (that is, in the case of holding a patient with Kaposi's sarcoma lesions versus one without) and in the case of a patient with AIDS (versus an HIV seropositive, asymptomatic patient). Results showed that exaggerated perceptions of risk were correlated with a lack of knowledge and with negative HIV-related attitudes. The study indicates the need for AIDS education that addresses biomedical findings and fact while concurrently addressing perceptions that may preclude the assimilation and application of such knowledge.

UDP glucuronosyltransferase 1A expression levels determine the response of colorectal cancer cells to the heat shock protein 90 inhibitor ganetespib.

HSP90 inhibition represents a promising route to cancer therapy, taking advantage of cancer cell-inherent proteotoxic stress. The HSP90-inhibitor ganetespib showed benefit in advanced clinical trials. This raises the need to identify the molecular determinants of treatment response. We tested the efficacy of ganetespib on a series of colorectal cancer (CRC)-derived cell lines and correlated their sensitivities with comprehensive gene expression analysis. Notably, the drug concentration required for 50% growth inhibition (IC50) varied up to 70-fold (from 36 to 2500 nM) between different cell lines. Correlating cell line-specific IC50s with the corresponding gene expression patterns revealed a strong association between ganetespib resistance (IC50>500 nM) and high expression of the UDP glucuronosyltransferase 1A (UGT1A) gene cluster. Moreover, CRC tumor samples showed a comparable distribution of UGT1A expression levels. The members of the UGT1A gene family are known as drug-conjugating liver enzymes involved in drug excretion, but their function in tumor cells is hardly understood. Chemically unrelated HSP90 inhibitors, for example, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), did not show correlation of drug sensitivities with UGT1A levels, whereas the ganetespib-related compound NVP-AUY922 did. When the most ganetespib-resistant cell line, HT29, was treated with ganetespib, the levels of HSP90 clients were unaffected. However, HT29 cells became sensitized to the drug, and HSP90 client proteins were destabilized by ganetespib upon siRNA-mediated UGT1A knockdown. Conversely, the most ganetespib-sensitive cell lines HCT116 and SW480 became more tolerant toward ganetespib upon UGT1A overexpression. Mechanistically, ganetespib was rapidly glucuronidated and excreted in resistant but not in sensitive CRC lines. We conclude that CRC cell-expressed UGT1A inactivates ganetespib and other resorcinolic Hsp90 inhibitors by glucuronidation, which renders the drugs unable to inhibit Hsp90 and thereby abrogates their biological activity. UGT1A levels in tumor tissues may be a suitable predictive biomarker to stratify CRC patients for ganetespib treatment.