Extended stereotactic brain biopsy in suspected primary central nervous system angiitis: good diagnostic accuracy and high safety

Journal of Neurology - To evaluate the diagnostic accuracy and safety of extended stereotactic brain biopsy (ESBB) in a single center cohort with suspected primary angiitis of the central nervous...     

A New Workflow for Whole‐Genome Sequencing of Single Human Cells

Unbiased amplification of the whole‐genome amplification (WGA) of single cells is crucial to study cancer evolution and genetic heterogeneity, but is challenging due to the high complexity of the human genome. Here, we present a new workflow combining an efficient adapter‐linker PCR‐based WGA method with second‐generation sequencing. This approach allows comparison of single cells at base pair resolution. Amplification recovered up to 74% of the human genome. Copy‐number variants and loss of heterozygosity detected in single cell genomes showed concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations could be determined accurately due to an allele dropout rate of only 2%, clearly demonstrating the low bias of our PCR‐based WGA approach. Sequencing with paired‐end reads allowed genome‐wide analysis of structural variants. By direct comparison to other WGA methods, we further endorse its suitability to analyze genetic heterogeneity.     

Eine faktorielle Studie von 6 Interventionen zur Vermeidung von Übelkeit und Erbrechen nach Narkosen

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.METHODS: In a randomized, controlled trial of factorial design, 5,199 patients at high risk for postoperative nausea and vomiting were randomly assigned to 1 of 64 possible combinations of 6 prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4) propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after surgery, which was evaluated blindly.RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics alone. All the interventions acted independently of each other and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. However, absolute risk reduction was a critical function of patients' baseline risk.CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.     

Occult tumor cells in lymph nodes as a predictor for tumor relapse in pancreatic adenocarcinoma

Background and aims Occurrence of tumor relapse is frequent in patients with pancreatic cancer despite the absence of residual tumor detectable at primary surgery and in histopathological examination. Therefore, it has to be assumed that current tumor staging procedures fail to identify minimal amounts of disseminated tumor cells, which might be precursors of subsequent metastatic relapse. The aim of this study was to assess the prognostic impact of minimal tumor cell spread detected in lymph nodes classified as “tumor-free” in routine histopathologic evaluation. Materials and methods A total of 154 “tumor-free” lymph nodes from 59 patients with pancreatic cancer who underwent intentionally curative tumor resection were examined by immunohistochemistry for disseminated tumor cells. Results Fifty (32.5%) of the “tumor-free” lymph nodes obtained from 36 (61%) patients displayed disseminated tumor cells. Multivariate survival analysis revealed that the presence of disseminated tumor cells in “tumor-free” lymph nodes is an independent prognostic factor for both a significantly reduced relapse-free survival (p = 0.03) and overall survival (p = 0.02). Conclusions The frequent occurrence and prognostic impact of immunohistochemically identifiable disseminated tumor cells in lymph nodes of patients with operable pancreatic cancer supports the need for a refined staging system of excised lymph nodes, which should include immunohistochemical examination.     

Challenges for CTC-based liquid biopsies: low CTC frequency and diagnostic leukapheresis as a potential solution

Circulating tumor cells (CTCs) are very attractive surrogate markers for systemic cancer. Currently, major efforts are being made to use these rare cells in the sense of a liquid biopsy to gain molecular information for rational therapeutic decision-making. The advancements in molecular analyses of CTCs down to the single-cell level have been significant in recent years and some applications are ready to be used in clinical studies. As discussed in this review, a major challenge for translating such molecular CTC-based assays into the clinic is the extremely low frequency of CTCs and the associated problems of their reliable detection and isolation. A potential solution to overcome the low CTC frequency is the recently introduced diagnostic leukapheresis that permits screening of liters of blood. Discussed here are the challenges as well as the current efforts implementing this method into clinical workflows to realize more reliable liquid biopsies.     

Predictive value of upper gastrointestinal studies versus clinical signs for gastrointestinal leaks after laparoscopic gastric bypass

Background The utility of routine upper gastrointestinal (UGI) studies after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a matter of great debate. Because the morbidity and mortality rates associated with an unrecognized postoperative leak are high after LRYGB, diagnosis of a postoperative leak earlier would be of benefit. Clinical signs, however, may predict the diagnosis of a postoperative leak more often. This study explored the hypothesis that UGI studies are more predictive than clinical signs for the early diagnosis of a postoperative leak after LRYGB. Methods All patients who underwent LRYGB at the authors’ institution were included in this study. Charts were reviewed to examine immediate clinical signs (heart rate, temperature, and white blood cell count within the first 24 h), UGI studies, and clinical course. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of clinical signs and UGI studies were calculated. Results This study included 245 patients with a 3% rate of leak. The positive and negative predictive value of UGI studies were 67% and 99%, respectively. Only an elevated white blood count had a better predictive value (100% for negative predictive value). The efficiency of UGI studies (98%) was better than that of heart rate (83%), white blood count (8%), or temperature (95%). Conclusions According to our data, UGI studies are the most predictive of an early leak diagnosis. Clinical signs alone may not be as useful in predicting leaks early after laparoscopic gastric bypasses. Routine early postoperative UGI studies are a reasonable approach to predicting leaks after LRYGB.     

PONV: a problem of inhalational anaesthesia?

Even nowadays every third or fourth patient suffers from postoperative nausea and vomiting (PONV) after general anaesthesia with volatile anaesthetics. There is now strong evidence that volatile anaesthetics are emetogenic and that there are no meaningful differences between halothane, enflurane, isoflurane, sevoflurane, and desflurane in this respect. However, when propofol is substituted for volatile anaesthetics the risk for PONV is reduced by only about one fifth, indicating that there are other even more important causes for PONV following general anaesthesia. A main causative factor might be the use of perioperative opioids, but their impact--relative to other factors including volatile anaesthetics--has never been quantified. Patient-specific risk factors have also been shown to be clinically relevant; they are therefore included in the calculation of simplified risk scores that allow prediction of a patient's risk independent of the type of surgery. Although controversial, the well-known different incidences following certain types of surgery are most likely caused by patient-specific and anaesthesia-related risk factors. There is a common consensus that prophylaxis with anti-emetic strategies is rarely justified when the risk of PONV is low, while it is warranted in case of imminent medical risk associated with vomiting or in a patient with a high risk for PONV. A recently published large multicentre trial of factorial design, IMPACT, has demonstrated that various anti-emetic strategies are associated with a very similar and constant relative reduction rate of about 25-30% and that the main predictor for the efficacy of prophylaxis is the patient's risk for PONV. Interestingly, all anti-emetics (dexamethasone, droperidol and ondansetron) work independently, so that their combined benefit can be derived directly from the single effects. The effectiveness of the anti-emetics was also independent of a variety of risk factors, including volatile anaesthetics. This means that any anti-emetic prophylaxis for PONV induced by volatile anaesthetics is equally effective. Of course, the most logical approach for prevention would be the omission of volatile anaesthetics and nitrous oxide using a total intravenous anaesthesia with propofol. However, since volatile anaesthetics are probably not the most important risk factors, it might be even better--if appropriate--to avoid general anaesthesia by using a regional, opioid-free anaesthesia if PONV is a serious problem.     

Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer

The increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12-21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death.