Background
Anastomotic leakage after esophagectomy is a life-threatening complication. No comparative outcome analyses for the different treatment regimens are yet available.
Methods
In a ...single-center study, data from all esophagectomy patients from January 1995 to January 2012, including tumor characteristics, surgical procedure, postoperative anastomotic leakage, leakage therapy regimens, APACHE II scores, and mortality, were collected, and predictors of patient survival after anastomotic leakage were analyzed.
Results
Among 366 resected patients, 62 patients (16 %) developed an anastomotic leak, 16 (26 %) of whom died. Therapy regimens included surgical revision (
n
= 18), endoscopic endoluminal vacuum therapy (
n
= 17), endoscopic stent application (
n
= 12), and conservative management (
n
= 15). APACHE II score at the initiation of treatment for leakage was the strongest predictor of in-hospital mortality (
p
< 0.0017). Conservatively managed patients showed mild systemic illness (mean APACHE II score 5) and no mortality. In systemically ill patients matched for APACHE II scores (mean, 14.4), endoscopic endoluminal vacuum therapy patients had lower mortality (12 %) compared to surgically treated (50 %,
p
= 0.01) cases and patients managed by stent placement (83 %,
p
= 00014, log rank test). No other clinical or laboratory parameters significantly influenced patient survival.
Conclusions
Endoscopic endoluminal vacuum therapy was the best treatment of anastomotic leakage in systemically ill patients after esophagectomy in this retrospective analysis. It should therefore be considered an important instrument in the management of this disorder.
Purpose: Aim of this study was to investigate the association between postdiagnosis body mass index (BMI) and all-cause mortality in colorectal cancer (CRC) survivors in a prospective study and ...meta-analysis. Methods: We conducted a prospective cohort study on 2,143 CRC survivors in Germany. Participants were recruited to the study on average 4 years after diagnosis, and postdiagnosis BMI was assessed at recruitment using a self-administered questionnaire. CRC survivors were followed up for a mean time of 3.5 years. The association between BMI and all-cause mortality was investigated using multivariable Cox proportional hazards models. Additionally, we performed a meta-analysis of studies on postdiagnosis BMI and all-cause mortality (n = 5, including this study) by applying random-effects models. Results: In the prospective analysis, 349 participants died. BMI was not statistically significantly associated with all-cause mortality. Compared to normal weight survivors, the hazard ratios (HRs) 95 % confidence interval (CI) for all-cause mortality in underweight, overweight and obese survivors were 1.65 (0.79–3.45), 0.80 (0.62–1.03) and 0.84 (0.62–1.14), respectively. In the meta-analysis, individuals with underweight were at increased risk for all-cause mortality HR (95 % CI) 1.72 (1.18–2.49), whereas individuals with overweight had a lower risk HR (95 % CI) 0.79 (0.71–0.88), compared to normal weight subjects. For obesity, the risk of mortality was also reduced with only borderline significance HR (95 % CI) 0.88 (0.77–1.00). Conclusions: While the present study as well as single previously published studies showed that overweight was associated with a non-significant reduced risk for all-cause mortality, our meta-analysis indicated a decreased mortality risk among overweight CRC survivors.
A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes ...across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using ...high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.
In type 2 diabetes (T2D), hepatic insulin resistance is strongly associated with non-alcoholic fatty liver disease (NAFLD). In this study, we hypothesized that DNA methylome of livers from patients ...with T2D, when compared to livers of individuals with normal plasma glucose levels, can unveil some mechanism of hepatic insulin resistance that could link to NAFLD. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in
(encoding platelet derived growth factor alpha) and
overexpression are associated with increased T2D risk, hyperinsulinemia, increased insulin resistance and increased steatohepatitis risk. Both genetic risk score studies and human cell modeling pointed to a causative impact of high insulin levels on
CpG site hypomethylation,
overexpression, and increased PDGF-AA secretion from liver. We found that PDGF-AA secretion further stimulates its own expression through protein kinase C activity and contributes to insulin resistance through decreased expression of both insulin receptor substrate 1 and of insulin receptor. Importantly, hepatocyte insulin sensitivity can be restored by PDGF-AA blocking antibodies, PDGF receptor inhibitors and by metformin opening therapeutic avenues. Therefore, in the liver of obese patients with T2D, the increased PDGF-AA signaling contributes to insulin resistance, opening new therapeutic avenues against T2D and possibly NAFLD.
RNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease H2 subunits A, B, and C), that cleaves RNA:DNA hybrids and removes mis-incorporated ribonucleotides from genomic DNA through ...ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and produces the most frequent type of naturally occurring DNA lesion. We investigated whether intestinal epithelial proliferation requires RNase H2 function and whether RNase H2 activity is disrupted during intestinal carcinogenesis.
We generated mice with epithelial-specific deletion of ribonuclease H2 subunit B (H2bΔIEC) and mice that also had deletion of tumor-suppressor protein p53 (H2b/p53ΔIEC); we compared phenotypes with those of littermate H2bfl/fl or H2b/p53fl/fl (control) mice at young and old ages. Intestinal tissues were collected and analyzed by histology. We isolated epithelial cells, generated intestinal organoids, and performed RNA sequence analyses. Mutation signatures of spontaneous tumors from H2b/p53ΔIEC mice were characterized by exome sequencing. We collected colorectal tumor specimens from 467 patients, measured levels of ribonuclease H2 subunit B, and associated these with patient survival times and transcriptome data.
The H2bΔIEC mice had DNA damage to intestinal epithelial cells and proliferative exhaustion of the intestinal stem cell compartment compared with controls and H2b/p53ΔIEC mice. However, H2b/p53ΔIEC mice spontaneously developed small intestine and colon carcinomas. DNA from these tumors contained T>G base substitutions at GTG trinucleotides. Analyses of transcriptomes of human colorectal tumors associated lower levels of RNase H2 with shorter survival times.
In analyses of mice with disruption of the ribonuclease H2 subunit B gene and colorectal tumors from patients, we provide evidence that RNase H2 functions as a colorectal tumor suppressor. H2b/p53ΔIEC mice can be used to study the roles of RNase H2 in tissue-specific carcinogenesis.
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Background
Endoscopic and laparoscopic electrosurgical devices (ED) are of great importance in modern medicine but can cause adverse events such as tissue injuries and burns from residual heat. While ...laparoscopic tools are well investigated, detailed insights about the temperature profile of endoscopic knives are lacking. Our aim is to investigate the temperature and the residual heat of laparoscopic and endoscopic monopolar instruments to increase the safety in handling ED.
Methods
An infrared camera was used to measure the temperature of laparoscopic and endoscopic instruments during energy application and to determine the cooling time to below 50 °C at a porcine stomach. Different power levels and cutting intervals were studied to investigate their impact on the temperature profile.
Results
During activation, the laparoscopic hook exceeded 120 °C regularly for an up to 10 mm shaft length. With regards to endoknives, only the Dual Tip Knife showed a shaft temperature of above 50 °C. The residual heat of the laparoscopic hook remained above 50 °C for at least 15 s after activation. Endoknives cooled to below 50 °C in 4 s. A higher power level and longer cutting duration significantly increased the shaft temperature and prolonged the cooling time (
p
< 0.001).
Conclusion
Residual heat and maximum temperature during energy application depend strongly on the chosen effect and cutting duration. To avoid potential injuries, the user should not touch any tissue with the laparoscopic hook for at least 15 s and with the endoknives for at least 4 s after energy application. As the shaft also heats up to over 120 °C, the user should be careful to avoid tissue contact during activation with the shaft. These results should be strongly considered for safety reasons when handling monopolar ED.
Symptomatic colon lipoma is a rare occurrence in clinical practice, and its association with sigmoid volvulus is even rarer. We present a case of a man in his 70s who presented to our emergency ...department with suspected intestinal obstruction. Upon examination, sigmoid volvulus was diagnosed and successfully treated endoscopically through decompression and detorsion. However, the patient experienced a recurrence, leading to the decision to perform sigmoid resection as a Hartmann’s procedure. Subsequently, a prolapsed tumor was observed through the stoma, which was endoscopically resected, revealing a pedunculated submucous colonic lipoma. This case report highlights the potential association between sigmoid volvulus and the presence of a large colon lipoma. Thus, giant colonic lipoma should be considered as a differential diagnosis among the causes of colonic volvulus.
Liquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating ...tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics.
In total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE
cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters.
Detection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE
method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE
for CTC detection.
Our study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine.
Background Esophageal perforation is a serious disease with a high morbidity and mortality rate. Endoscopic vacuum therapy (EVT) is a new endoscopic treatment option, which is used to treat ...anastomotic leakages after rectal and esophageal resections. We report on 10 patients treated with EVT for esophageal perforation. Methods Clinical and therapy-related data such as age, sex, duration of intensive care stay, length of hospital stay, reasons for perforation, EVT-associated complications, mortality, need for alternative treatment options, and course of infectious variables were analyzed. Results Ten patients were treated with 54 vacuum sponges that were placed in upper gastrointestinal defects. Causes for perforation were iatrogenic, spontaneous, or foreign body-associated. Mean number of sponge insertions was 5.4 (range, 2 to 12) with a mean period of 19 ± 14.26 days. Successful therapy was achieved in 9 of 10 patients. After successful primary treatment, 1 patient died during therapy as a result of general failure of the cardiovascular system. In 1 patient, surgical resection was necessary after repeated Mallory-Weiss lesions and minor perforations during the course of immunosuppressive therapy. In a third patient an endoscopic stent was inserted in the clean wound cavity after primary EVT. Conclusions In this small trial EVT has been shown to be a safe and feasible therapy option for perforations of the upper gastrointestinal tract. If necessary, EVT can be combined with operative revision for better control of the local septic focus or used as a bridging procedure for wound conditioning before aggressive surgical treatment.
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