Is there a weekend effect in emergency surgery for colorectal carcinoma? Analysis from the German StuDoQ registry.

BACKGROUND: Higher postoperative mortality has been observed among patients who received emergency colorectal surgery on the weekend compared to during the week. The aim of this study was to determine whether the weekday of emergency surgery affects the 30-day mortality and postoperative course in emergency colorectal surgery. METHODS: Prospectively acquired data from the 2010-2017 German StuDoQ|Colorectal surgery registries were analysed. Differences in 30-day mortality, transfer and length of stay (MTL30) (primary endpoints), postoperative complications, length of stay and pathological results of resected specimens (secondary endpoints) were assessed. Multivariable analysis was performed to identify independent risk factors for postoperative outcome. RESULTS: In total, 1,174 patients were included in the analysis. Major postoperative complications and the need for reoperation were observed more frequently for emergency colorectal surgery performed during the week compared to the weekend (23.01 vs. 15.28%, p = 0.036 and 17.96% vs. 11.11%, p = 0.040, respectively). In contrast, patients who received emergency surgery on the weekend presented with significantly higher UICC tumour stages (UICC III 44.06 vs. 34.15%, p = 0.020) compared to patients with emergency colorectal surgery on a weekday. Emergency surgery performed during the week was an independent risk factor for the development of severe postoperative complications (OR 1.69 [1.04-2.74], p = 0.033) and need for reoperation (OR 1.79 [1.02-3.05], p = 0.041) in the multivariable analysis. CONCLUSION: Emergency surgery for colorectal carcinoma in Germany is performed with equal postoperative MTL30 and mortality throughout the entire week. However, emergency surgery during the week seems to be associated with a higher rate of severe postoperative complications and reoperation.

Disease- and Medication-Specific Differences of the Microbial Spectrum in Perianal Fistulizing Crohn's Disease-Relevant Aspects for Antibiotic Therapy.

Perianal fistulizing Crohn's Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future.

Does Concurrent Cholestasis Alter the Prognostic Value of Preoperatively Elevated CA19-9 Serum Levels in Patients with Pancreatic Head Adenocarcinoma?

BACKGROUND: Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified. METHODS: Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values. RESULTS: Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 %) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 % of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment. CONCLUSIONS: In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients.

Mucosa and microbiota - the role of intrinsic parameters on intestinal wound healing.

Mucosal healing in the gut is an essential process when it comes to chronic inflammatory disorders such as inflammatory bowel diseases (IBD) but also to the creation of intestinal anastomosis. Despite an improvement of surgical techniques, the rates of anastomotic leakage remain substantial and represent a significant health-care and socio-economic burden. Recent research has focused on intrinsic factors such as mucosal linings and differences in the intestinal microbiota and identified specific endoluminal bacteria and epithelial proteins which influence intestinal wound healing and re-establishment of mucosal homeostasis. Despite the lack of large clinical studies, previous data indicate that the identified bacteria such as aerotolerant lactobacilli or wound-associated Akkermansia muciniphila as well as epithelial-expressed sialyl Lewis glycans or CD47 might be critical for wound and anastomotic healing in the gut, thus, providing a potential novel approach for future treatment strategies in colorectal surgery and IBD therapy. Since microbiota and mucosa are interacting closely, we outline the current discoveries about both subsets in this review together to demonstrate the significant interplay.

Microbial Spectrum and Antibiotic Resistance in Patients Suffering from Penetrating Crohn's Disease.

Intraabdominal abscess formation occurs in up to 30% of patients suffering from Crohn´s disease (CD). While international guidelines recommend a step-up approach with a combination of empiric antibiotic therapy and percutaneous drainage to delay or even avoid surgery, evidence about microbial spectrum in penetrating ileitis is sparse. We retrospectively assessed outcomes of 46 patients with terminal penetrating Ileitis where microbial diagnostics have been performed and compared microbial spectrum and antibiotic resistance profile of CD patients with patients suffering from diverticulitis with intraabdominal abscess formation. In both groups, the most frequently isolated pathogen was the gram-negative bacterium E.coli belonging to the family of Enterobacterales. However, overall Enterobacterales were significantly more often verifiable in the control group than in CD patients. Furthermore, microbial analysis showed significant differences regarding isolation of anaerobic pathogens with decreased frequency in patients with CD. Subgroup analysis of CD patients to evaluate a potential influence of immunosuppressive therapy on microbial spectrum only revealed that Enterobacterales was less frequently detected in patients treated with steroids. Immunosuppressive therapy did not show any impact on all other groups of pathogens and did not change antibiotic resistance profile of CD patients. In conclusion, we were able to demonstrate that the microbial spectrum of CD patients does differ only for some pathogen species without increased rate of antibiotic resistance. However, the empiric antibiotic therapy for CD-associated intra-abdominal abscess remains challenging since different points such as local epidemiological and microbiological data, individual patient risk factors, severity of infection, and therapy algorithm including non-surgical and surgical therapy options should be considered before therapeutical decisions are made.

Safety of elective abdominal and vascular surgery during the COVID-19 pandemic: a retrospective single-center study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission. METHODS: The screening program comprised polymerase chain reaction (PCR) testing of nasopharyngeal swabs and a standardized questionnaire about potential symptoms for SARS-CoV-2 infection. All elective and emergency patients admitted to the surgical department of a tertiary-care hospital center in Lower Franconia, Germany, between March and May 2020 were included and their characteristics were recorded. RESULTS: Out of the study population (n = 657), 509 patients (77.5%) had at least one risk factor for a potentially severe course of COVID-19 and 164 patients (25%) were active smokers. The average 7-day incidence in Lower Franconia was 24.0/100,000 during the observation period. Preoperative PCR testing revealed four asymptomatic positive patients out of the 657 tested patients. No postoperative SARS-CoV-2 infection or transmission could be detected. CONCLUSION: The implementation of a standardized preoperative screening program to both COVID-19 and non-COVID-19 patients can ensure high-quality surgical care while minimizing infection risk for healthcare workers and potential in-hospital transmission.

Preoperative Liver Function Guiding HCC Resection in Normal and Cirrhotic Liver.

BACKGROUND: Liver resection is the most effective available therapy for patients with hepatocellular carcinoma (HCC). The accurate selection of patients for surgery requires determination of technical resectability and the risk of recurrence, as well as assessment of liver function and functional reserve to avoid postoperative liver failure. Previous studies have underlined the effectiveness and reliability of the LiMAx® test to evaluate liver function preoperatively. Nevertheless, data concerning HCC evaluation are lacking. METHODS: From 2014 to 2019, 92 patients with HCC underwent additional assessment of liver function using the LiMAx test prior to decision for or against liver resection. Preoperative LiMAx results were compared between cirrhotic and noncirrhotic liver. The clinical decision for surgery was evaluated applying the various liver function parameters available. RESULTS: Forty-six patients underwent liver resection. The LiMAx results were higher in resected patients (388 vs. 322 µg/kg/h; p = 0.004). LiMAx values were an independent risk factor for the presence of liver cirrhosis in multivariate analysis. In 17 patients, surgical treatment was cancelled due to major impairment of liver function. Only 4 out of 46 resected patients presented with post-hepatectomy liver failure (PHLF) grade ≥B. Histologic assessment revealed liver cirrhosis in 10 resected patients without PHLF. CONCLUSION: Preoperative determination of liver function by the LiMAx test enables effective and safe patient selection for HCC resection in both cirrhotic and noncirrhotic liver.

Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study.

BACKGROUND: A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. METHODS: In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. RESULTS: Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS. CONCLUSION: Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

Early Ileocecal Resection Is an Effective Therapy in Isolated Crohn's Disease.

Despite the increasing incidence and prevalence of Crohn's Disease (CD), no curative options exist and treatment remains complex. While therapy has mainly focused on medical approaches in the past, growing evidence reveals that in cases of limited inflammation, surgery can suffice as an alternative primary treatment. We retrospectively assessed the disease course and outcomes of 103 patients with terminal Ileitis who underwent primary surgery (n = 29) or received primary medical treatment followed by surgery (n = 74). Primary endpoint was the need for immunosuppressive medication after surgical treatment (ileocecal resection, ICR) during a two-years follow-up. Rates for laparoscopic ICR were enhanced in case of early surgery, but no differences were seen for postoperative complications. In case of immunosuppressive medication, patients with ICR at an early state of disease needed significantly less anti-inflammatory medication during the two-year postoperative follow-up compared to patients who were primarily treated medically. Furthermore, in a subgroup analysis for patients with localized ileocecal disease manifestation, early surgery consistently resulted in a decreased amount of medical therapy postoperatively. In conclusion primary ICR is safe and effective in patients with limited CD, and the need for immunosuppressive medication during the postoperative follow-up is low compared to patients receiving surgery at a later stage of disease.

Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria.

BACKGROUND: International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. METHODS: Patients' tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed. RESULTS: A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS. CONCLUSIONS: Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.

The Effect of Day of the Week on Morbidity and Mortality From Colorectal and Pancreatic Surgery.

BACKGROUND: A number of studies have revealed higher postoperative mortality after operations that were performed toward the end of the week. It is not yet known whether a day-of-the-week effect exists after visceral surgical procedures for cancer in Germany. METHODS: Data on resections of carcinomas of the colon, rectum (2010-2017), and head of the pancreas (2014-2017) (n = 19 703) that had been prospectively acquired by the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery were analyzed in relation to the day of the week on which the operation was performed. The primary endpoint was postoperative 30-day mortality; the secondary endpoints were complications, length of hospital stay, and MTL30 (a combined outcome criterion that is positive if the patient has died, is still in the hospital, or has been transferred to another acute care hospital 30 days after the index procedure). RESULTS: Resections of colon carcinomas that were performed on Mondays were associated with more advanced tumor stages (T4: 18.4% vs. 15.7%, p <0.001), higher 30-day mortality (3.5% vs. 2.3%, p = 0.004), and a more frequently positive MTL30 (10.5% vs. 8.5%, p = 0.004). Among patients who underwent pancreatic head resections, those whose procedures were on Tuesday had higher mortality (6.2% vs. 3.8%; p = 0.021). Among those who underwent surgery for rectal carcinoma, the day of the week on which the procedure was performed had no effect on postoperative morality. Multivariate analysis revealed that the independent risk factors for postoperative mortality were colonic resection on a Monday (odds ratio [OR]: 1.45; 95% confidence interval [1.11; 1.92], p = 0.008) and pancreatic head resection on a Tuesday (OR: 1.88 [1.18; 2.91], p = 0.006). CONCLUSION: Elective surgery for carcinoma of the colon or pancreatic head is associated with slightly higher mortality if per - formed toward the beginning of the week. On the other hand, the day of the week has no effect on the outcome of surgery for rectal carcinoma.

Prognostic impact of simultaneous venous resections during surgery for resectable pancreatic cancer.

BACKGROUND: The aim of this study was to evaluate the prognostic impact of simultaneous venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) that was preoperatively staged resectable according to NCCN guidelines. METHODS: A retrospective analysis of 153 patients who underwent PD for PDAC was performed. Patients were divided into standard PD and PD with simultaneous vein resection (PDVR). Groups were compared to each other in terms of postoperative morbidity and mortality, disease free (DFS) and overall survival (OS). RESULTS: 114 patients received PD while 39 patients received PDVR. No differences in terms of postoperative morbidity and mortality between both groups were detected. Patients in the VR group presented with a significantly shorter OS in the median (13 vs. 21 months, P = 0.011). In subgroup analysis, resection status did not influence OS in the PDVR group (R0 13 vs. R1 12 months, P = 0.471) but in the PD group (R0 23 vs. R1 14 months, P = 0.043). PDVR was a risk factor of OS in univariate but not multivariable analysis. CONCLUSION: PDVR for PDAC preoperatively staged resectable resulted in significantly shorter OS regardless of resection status. Patients who require PDVR should be considered for adjuvant chemotherapy in addition to other oncological indications.

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry.

BACKGROUND: Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks. METHODS: This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of "less than 6 weeks", "6 to 8 weeks", "8 to 10 weeks" and "more than 10 weeks". Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification. RESULTS: Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5%) and pGR (22.6%) in "8 to 10" and "more than 10" weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality. CONCLUSION: A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity.

The local immune phenotype influences prognosis in patients with nodal-positive rectal cancer after neoadjuvant chemoradiation.

INDROCUTION: The local immune contexture in patients with locally advanced rectal cancer (LARC) has important prognostic value after neoadjuvant chemoradiation and surgical resection. In this study, we examined the prognostic role of Indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) according to the nodal stage of LARC patients. MASTERIAL AND METHODS: Expression of IDO1 and CD8 was evaluated through immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated and expressed as total scores as previously described. Kaplan-Meier curves were used to describe overall and disease-free survival. RESULTS: In nodal-positive tumours (N+), IDO-positivity was associated with a reduced disease-free survival (DFS) (p = 0.063) and CD8-positivity with an impaired OS (p = 0.024). Patients with a N+ LARC and a high total IDO1 score showed a clear advantage regarding five-year disease-free survival rates compared with patients with a low total IDO1 score (N+ 5y-DFS IDO1 high: 66.7% vs IDO low: 19%). We also detected better 5-years-OS rates in N+ LARC with a high total CD8 score (N+ 5y-OS CD8 high: 83.3% vs CD8 low: 32.3%). These survival benefits were not evident in patients with N-tumours. CONCLUSION: Analysis of the local CD8 and IDO1 expression influences prognosis in nodal-positive LARC patients after multimodal therapy and may be a helpful tool in specifying individual adjuvant treatment strategies according to different immune profiles.

Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Improve Liver Regeneration After Ischemia Reperfusion Injury in Mice.

Hepatic ischemia reperfusion injury (IRI) remains a major obstacle in liver resection and transplantation surgery, especially in diseased organs. Human mesenchymal stromal cells (MSCs) are reported to acutely alleviate hepatic IRI in mice by releasing bioactive membrane-enclosed extracellular vesicles (EVs), but the long-term effects of MSC-derived EV on hepatic IRI are unknown. Given the considerable differentiation capacity of fibroblasts (FBs) during wound healing and their morphological similarities with MSC, the present study aimed to investigate the potential of these two cell types and their cell-derived EV in attenuating liver damage after IRI. EVs were isolated and purified from the supernatant of MSC and FB cultures and, subsequently, characterized by electron microscopy, nanoparticle tracking analysis, and western blot. Liver injury and organ regeneration in a murine in vivo model of IRI were assessed by serum transaminase levels, histopathology, and immunohistochemistry. Changes in expression of inflammation-associated genes within liver tissue were evaluated by reverse transcriptase quantitative polymerase chain reaction. MSC, MSC-derived EV, FB, and FB-derived EV were systemically administered before hepatic IRI. We found that MSC and MSC-derived EV decreased serum transaminase levels, reduced hepatic necrosis, increased the amount of Ki67-positive hepatocytes, and repressed the transcription of inflammation-associated genes. Although they had no impact on organ damage, FB and FB-derived EV showed some regenerative potential in the late phase of hepatic IRI. Compared to FB, MSC and their derived EV had a stronger potential to attenuate liver damage and improve organ regeneration after hepatic IRI. These results suggest that the key therapeutic factors are located within EV.

Impact of different emulsifiers on biocompatibility and inflammatory potential of Perfluorohexyloctane (F6H8) emulsions for new intravenous drug delivery systems.

BACKGROUND: Emulsions on the basis of Perfluorohexyloctane (F6H8), a semifluorinated alkane (SFA), have shown to dissolve and transport highly lipophilic compounds. It is unknown how F6H8-containing emulsions (F6H8-cEM) interact with compartment blood, the reticuloendothelial system (RES), or influence injured organs in vivo. The current study was conducted to investigate the in vitro biocompatibility of F6H8-cEM and their drug delivery properties. Afterward, an in vivo study was performed as a proof-of-concept study in a rat model of acute kidney injury (AKI), which focused on the potential influence of F6H8-cEM on inflammation in an injured organ. METHODS: Two different F6H8-cEM were stabilized by the emulsifying agents Poloxamer 188 (Pluronic® F68) or lecithin (S75). The two resulting emulsions F6H8-Pluronic or F6H8-lecithin were tested in vitro for the potential modulation of acute inflammation via whole blood assay, FACS, and ELISA. Antioxidant capacity and drug delivery properties were measured with an oxidation assay. Secondly, AKI was induced in the rats, which were treated with the F6H8-lecithin emulsion. Renal function and inflammation were assessed. RESULTS: Both F6H8-cEM were phagocytized by monocytes and both dose-dependently affected apoptosis (Annexin V binding) in monocytes. TNF-α expression increased dose-dependency for F6H8-Pluronic emulsion but not for F6H8-lecithin in a whole blood assay. Both F6H8-cEM were able to carry α-tocopherol as a model drug. Animals with AKI treated with the F6H8-lecithin emulsion showed a significantly better renal function and less infiltration of inflammatory cells in renal tissue compared to the control, while inflammatory markers in renal tissue, except HO-1, were not affected by F6H8-lecithin. CONCLUSIONS: Pluronic® F68 does not seem suitable as a biocompatible surfactant for F6H8-cEM. The injured kidney was not negatively influenced by the F6H8-lecithin emulsion. Lecithin-stabilized F6H8-cEM could be tested for preclinical studies as a carrier system for lipophilic agents.