Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.

MASLD is related to impaired alcohol dehydrogenase (ADH) activity and elevated blood ethanol levels: Role of TNFα and JNK.

Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα-/- mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα-/- mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In in vitro models, TNFα but not IL-1ß or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.

Intraoperative bacterial cultures fail to reliably predict the bacterial spectrum encountered during infectious complications after appendicitis.

Acute appendicitis is a common surgical emergency. Complicated appendicitis usually warrants perioperative antibiotic treatment in order to prevent infectious complications. Whether routine microbiological testing benefits the individual patient is a topic of debate. The goal of our study was to assess perioperative antibiotic prescriptions as well as the benefit of microbiological testing during the appendectomy as a predictor for bacteria encountered in infectious complications. This is a retrospective analysis of 1218 consecutive patients that underwent appendectomy at a tertiary referral center between 2014 and 2021. The patient charts were systematically analyzed regarding intraoperative outcome, microbiologic results, and postoperative infectious complications. 1218 patients were included in this study of which 768 were uncomplicated appendicitis (UA) and 450 were complicated appendicitis (CA). Microbiological testing was performed in 39.2% of UA cases (33.6% of which grew bacteria) compared to 74.9% of CA cases (78.6% positive cultures). The strongest individual predictors for SSI were gangrenous and perforated appendicitis. A total of 58 surgical-site infections developed, of which 49 were intra-abdominal fluid collections or abscesses. Thirty-two patients had revision surgery or CT-guided drainage for SSI. In the cases where microbiological testing was done both during the appendectomy and the SSI, 13/18 showed different bacteria on culture testing. The infectious outcome was favorable in 98.3%. While microbiological testing offers insights into resistance patterns, it is of little benefit for the individual patient, given the low predictive value for bacteria found during SSI. Achieving source control combined with empiric antibiotic coverage leads to favorable outcomes independent of culture results.

Predicting complicated appendicitis is possible without the use of sectional imaging-presenting the NoCtApp score.

PURPOSE: Appendicitis is among the most common acute conditions treated by general surgery. While uncomplicated appendicitis (UA) can be treated delayed or even non-operatively, complicated appendicitis (CA) is a serious condition with possible long-term morbidity that should be managed with urgent appendectomy. Distinguishing both conditions is usually done with computed tomography. The goal of this study was to develop a model to reliably predict CA with widespread available clinical and laboratory parameters and without the use of sectional imaging. METHODS: Data from 1132 consecutive patients treated for appendicitis between 2014 and 2021 at a tertiary care hospital were used for analyses. Based on year of treatment, the data was divided into training (n = 696) and validation (n = 436) samples. Using the development sample, candidate predictors for CA-patient age, gender, body mass index (BMI), American Society of Anesthesiologist (ASA) score, duration of symptoms, white blood count (WBC), total bilirubin and C-reactive protein (CRP) on admission and free fluid on ultrasound-were first investigated using univariate logistic regression models and then included in a multivariate model. The final development model was tested on the validation sample. RESULTS: In the univariate analysis age, BMI, ASA score, symptom duration, WBC, bilirubin, CRP, and free fluid each were statistically significant predictors of CA (each p < 0.001) while gender was not (p = 0.199). In the multivariate analysis BMI and bilirubin were not predictive and therefore not included in the final development model which was built from 696 patients. The final development model was significant (x2 = 304.075, p < 0.001) with a sensitivity of 61.7% and a specificity of 92.1%. The positive predictive value (PPV) was 80.4% with a negative predictive value (NPV) of 82.0%. The receiver operator characteristic of the final model had an area under the curve of 0.861 (95% confidence interval 0.830-0.891, p < 0.001. We simplified this model to create the NoCtApp score. Patients with a point value of ≤ 2 had a NPV 95.8% for correctly ruling out CA. CONCLUSIONS: Correctly identifying CA is helpful for optimizing patient treatment when they are diagnosed with appendicitis. Our logistic regression model can aid in correctly distinguishing UA and CA even without utilizing computed tomography.

Primary admission to a surgical service facilitates early cholecystectomy in acute cholecystitis but does not influence patient outcome.

PURPOSE: Early cholecystectomy is recommended for acute calculous cholecystitis to reduce complications and lower health care costs. However, not all patients admitted to emergency services due to acute calculous cholecystitis are considered for surgery immediately. Our intention was therefore to evaluate patient management and outcome parameters following cholecystectomy depending on the type of emergency service patients are primarily admitted to. METHODS: We performed a retrospective analysis of all patients that were treated for acute cholecystitis at our hospital between 2014 and 2021. Only patients that underwent surgical treatment for acute calculous cholecystitis were included. Patients with cholecystectomies that were performed due to other medical conditions were not incorporated. Primary outcomes were the perioperative length of stay and postoperative complications. Perioperative antimicrobial management and disease deterioration according to Tokyo Guidelines from 2018 due to inhouse organization were assessed as secondary outcome parameters. RESULTS: Of 512 patients included in our final analysis, 334 patients were primarily admitted to a surgical emergency service (SAG) whereas 178 were initially treated in a medical service (MAG). The latency between admission and cholecystectomy was significantly prolonged in the MAG with a median time to surgery of 2 days (Q25 1, Q75 3.25, IQR 2.25) compared to the SAG with a median time to surgery of 1 day (Q25 1, Q75 2, IQR 1) (p < 0.001). The duration of surgery was comparable between both groups. Necrotizing cholecystitis (27.2% vs. 38.8%, p = 0.007) and pericholecystic abscess or gallbladder perforation (7.5% vs. 14.6% p = 0.010) were less frequently described in the SAG. In the SAG, 85.7% of CCEs were performed laparoscopically, 6.0% were converted to open, and 10.4% were performed as open surgery upfront. In the MAG, 80.9% were completed laparoscopically, while 7.2% were converted and 11.2% were performed via primary laparotomy (p = 0.743). Histologically gangrenous cholecystitis was confirmed in 38.0% of the specimen in the SAG compared to 47.8% in the MAG (p = 0.033). While the prolonged preoperative stay led to prolonged overall length of stay, the postoperative length of stay was similar at a median of 3 days in both groups. CONCLUSIONS: To our knowledge, we present the largest single center cohort of acute calculous cholecystitis evaluating the perioperative management and outcome of patients admitted to either medical or surgical service prior to undergoing cholecystectomy. In patients that were primarily admitted to medical emergency services, we found disproportionately more gallbladder necrosis, perforation, and gangrene. Despite prolonged time intervals between admission and cholecystectomy in the MAG and advanced cases of cholecystitis, we did not record a prolonged procedure duration, conversion to open surgery, or complication rate. However, patients with acute calculous cholecystitis should either be primarily admitted to a surgical emergency service or at least a surgeon should be consulted at the time of diagnosis in order to avoid disease progression and unnecessary health care costs.

Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma.

BACKGROUND: Standard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (± chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and postoperative complications in patients treated with multimodal treatment. METHODS: Oncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in 74 patients with localized high-risk soft tissue sarcoma of extremities and trunk undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant vs. adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications. RESULTS: Oncologic outcomes were dependent on number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. Slightly higher MWC-rates were observed in patients treated with neoadjuvant therapy, compared to adjuvant radiotherapy, although only with a trend to statistical significance (31.8% vs. 13.3%, p = 0.059). However, except for wound infections, no significant difference for other subclasses of postoperative complications was observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications. CONCLUSION: Rates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Tumor localization, patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence DMFS. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.

Perioperative Antibiotics in Appendicitis-Do We Need to Adjust Therapy for the Elderly? A Matched Pair Analysis.

(1) Background: Perioperative Antibiotics for acute complicated appendicitis are a standard of care. While there are plenty of trials for pediatric patients, data for elderly patients are scarce. The goal of our study was to evaluate whether elderly patients carry more resistant bacteria and thus have less favorable outcomes after an appendectomy that may warrant intensified perioperative antibiotic treatment (2) We present a retrospective single-center matched pair (139 patients each) analysis of perioperative and microbiological outcomes of an elderly appendicitis cohort (i.e., older than 60 years) compared with a younger adult cohort (i.e., ≤60 years). Both groups were matched one for one according to gender, duration of symptoms, c-reactive protein at presentation and whether they presented with uncomplicated or complicated appendicitis. (3) Results: After matching, complicated appendicitis was present in 76.3% of both groups. Elderly patients more frequently received preoperative diagnostic CT (p < 0.001) than the young. Both operative strategy (laparoscopic appendectomy in 92.1% each) and duration of surgery (57 vs. 56 min) were equal in both groups. Postoperative antibiotics were prescribed in ~57% for a median of 3 days in both groups and antibiotic selection was similar. The incidence of surgical site infections was higher in the young (12.2% vs. 7.9%) yet not significant. There was no difference in culture positivity or bacterial spectrum and the elderly cohort did not present with increased resistant bacterial isolates. (4) Conclusions: While overall resistant bacterial strains were rare, perioperative outcomes between the young and the elderly did not differ and did neither warrant longer nor intensified antibiotic treatment.

Management of Symptomatic Gallstone Disease during COVID-19 Lockdown in a High-Resource Setting: Is There a Need for Treatment Alterations?

Introduction: Cholecystectomy (CCE) is the treatment of choice of symptomatic gallstones. Due to the SARS-CoV-2 pandemic, operating room (OR) capacities have been reduced. The goal of this study was to evaluate the duration of symptoms of patients presenting with gallstone disease during a lockdown, the surgical management, and the severity grade of their disease. Materials and Methods: A cohort study of 353 CCEs performed at a university hospital over two 10-week periods during 2 pandemic lockdowns in Germany compared to corresponding periods in 2018 and 2019. Results: During the lockdowns, 101 CCEs were performed compared to 252 in the prior years. The number of elective CCEs was reduced to save OR capacities (p < 0.001), and the most common indication for CCE was acute cholecystitis. The median time to CCE after symptom onset was 3 days in both groups for acute cholecystitis. The severity of cholecystitis was comparable (p = 0.760). The time to CCE after choledocholithiasis was shorter during the lockdowns (median of 4 days vs. 9 days; p = 0.006). Conclusions: The incidence and severity of acute cholecystitis during the lockdowns were comparable to the prior years. Acute care surgery was provided at the expense of elective procedures, and there was no need for treatment alterations.

Surgical Management of Sporadic Peripheral Nerve Schwannomas in Adults: Indications and Outcome in a Single Center Cohort.

Most sporadic peripheral nerve sheath tumors in adults are schwannomas. These tumors usually present with significant pain but can also cause neurological deficits. Symptomatology is diverse, and successful surgical interventions demand interdisciplinarity. We retrospectively reviewed 414 patients treated between 2006 and 2017 for peripheral nerve sheath tumors. We analyzed clinical signs, symptoms, histology, and neurological function in the cohort of adult patients with schwannomas without a neurocutaneous syndrome. In 144 patients, 147 surgical interventions were performed. Mean follow-up was 3.1 years. The indication for surgery was pain (66.0%), neurological deficits (23.8%), significant tumor growth (8.8%), and suspected malignancy (1.4%). Complete tumor resection was achieved on 136/147 occasions (92.5%). The most common location of the tumors was intraspinal (49.0%), within the cervical neurovascular bundles (19.7%), and lower extremities (10.9%). Pain and neurological deficits improved significantly (p ≤ 0.003) after 131/147 interventions (89.1%). One patient had a persistent decrease in motor function after surgery. Complete resection was possible in 67% of recurrent tumors, compared to 94% of primary tumors. There was a significantly lower chance of complete resection for schwannomas of the cervical neurovascular bundle as compared to other locations. The surgical outcome of sporadic schwannoma surgery within the peripheral nervous system is very favorable in experienced peripheral nerve surgery centers. Surgery is safe and effective and needs a multidisciplinary setting. Early surgical resection in adult patients with peripheral nerve sheath tumors with significant growth, pain, neurological deficit, or suspected malignancy is thus recommended.

Erratum: Prognostic relevance of high pretreatment CA125 levels in primary serous ovarian cancer.

[This corrects the article DOI: 10.3892/mco.2020.2170.].

Routine postoperative blood tests fail to reliably predict procedure-related complications after laparoscopic cholecystectomy.

PURPOSE: Laparoscopic cholecystectomy is a highly standardized surgical procedure with a low risk of complications. However, once complications develop, they can be life-threatening. The aim of this study was to evaluate the value of blood tests on postoperative day one regarding their potential to predict postoperative complications METHODS: A cohort study of 1706 consecutive cholecystectomies performed at a tertiary hospital and teaching facility over a 5-year period between 2014 and 2019. RESULTS: Patients that had open CCE or conversion CCE were excluded. One thousand five hundred eighty-six patients were included in the final analysis that received a laparoscopic cholecystectomy (CCE). One thousand five hundred twenty-three patients had blood tests on POD 1. Forty-one complications were detected including 14 bile leaks, 2 common bile duct injuries, 13 choledocholithiasis, 9 hematomas, and 2 active bleedings. Bilirubin was elevated in 351 patients on POD 1. A drop of more than 3 mg/dl of hemoglobin was reported in 39 patients. GPT was elevated 3 × above the upper limit in 102 patients. All three tests showed a low sensitivity and specificity in detecting postoperative complications. CONCLUSIONS: Early postoperative blood tests alone show a low specificity in detecting postoperative complications after laparoscopic CCE. Their main benefit appears to be the negative predictive value, when they are normal. Routine blood testing appears to be unnecessary and should be based on the intraoperative diagnosis and postoperative clinical findings.

The Prevalence and Clinical Significance of Anaerobic Bacteria in Major Liver Resection.

(1) Background: Anaerobic infections in hepatobiliary surgery have rarely been addressed. Whereas infectious complications during the perioperative phase of liver resections are common, there are very limited data on the prevalence and clinical role of anaerobes in this context. Given the risk of contaminated bile in liver resections, the goal of our study was to investigate the prevalence and outcome of anaerobic infections in major hepatectomies. (2) Methods: We retrospectively analyzed the charts of 245 consecutive major hepatectomies that were performed at the department of General, Visceral, and Transplantation Surgery of the University Hospital of Tuebingen between July 2017 and August 2020. All microbiological cultures were screened for the prevalence of anaerobic bacteria and the patients' clinical characteristics and outcomes were evaluated. (3) Results: Of the 245 patients, 13 patients suffered from anaerobic infections. Seven had positive cultures from the biliary tract during the primary procedure, while six had positive culture results from samples obtained during the management of complications. Risk factors for anaerobic infections were preoperative biliary stenting (p = 0.002) and bile leaks (p = 0.009). All of these infections had to be treated by intervention and adjunct antibiotic treatment with broad spectrum antibiotics. (4) Conclusions: Anaerobic infections are rare in liver resections. Certain risk factors trigger the antibiotic coverage of anaerobes.

Clinical Presentation and Incidence of Anaerobic Bacteria in Surgically Treated Biliary Tract Infections and Cholecystitis.

(1) Background: Cholecystitis and cholangitis are among the most common diseases treated by general surgery. Gallstones lead to inflammation and bacterial infection of the biliary tract. Biliary infections can lead to live threatening bacteremia and liver abscesses. The true role of anaerobes remains unclear. (2) Methods: We retrospectively analyzed bacterial cultures from biliary samples obtained from bile ducts and gallbladders at our tertiary care center. Patient characteristics and clinical outcomes were analyzed. (3) Results: In our database of 1719 patients, 365 patients had microbial testing, of which 42 grew anaerobic bacteria. Anaerobes were more frequently cultured in patients with hepatic abscesses and gallbladder perforation. These patients were older and had more comorbidities than the control group. The overall outcomes of all patients were favorable and the resistance rate to commonly used antibiotics remained low. (4) Conclusions: Anaerobes in biliary tract infections appear to be underdiagnosed and more prevalent in the elderly with advanced disease. Due to low antibiotic resistance, the combination of source control and adjunct anti-infective treatment leads to favorable outcomes.

Prognostic relevance of high pretreatment CA125 levels in primary serous ovarian cancer.

The objective of the present study was to analyze the prognostic relevance of pretreatment serum CA125 ≥500 U/ml and its role as a non-invasive factor for estimating optimal cytoreduction (≤1 cm) in primary serous ovarian cancer. Clinicopathological parameters and CA125 levels prior to primary cytoreductive surgery were retrospectively evaluated in all 261 consecutive patients with primary epithelial ovarian cancer from a single centre. Inclusion criteria were existing preoperative CA125 level, serous ovarian cancer and performed full primary treatment (surgery/platinum-based chemotherapy). A total of 136 patients met the criteria. Among them, 74 patients had CA125 ≥500 U/ml. The other 62 patients that met the aforementioned criteria and had CA125 <500 U/ml were defined as controls. The present study tested cut-off CA125 values to detect subgroups affecting prognosis. The goal was to evaluate patients with optimal cytoreduction (R≤1 cm). Univariate analyses were performed with PASW to identify clinicopathological parameters associated with the pretreatment CA125 level. For survival analyses, a cut-off-value of CA125 ≥500 U/ml was used to identify the association between preoperative CA125 levels, resection status and prognosis. To test significant differences between examined groups, Student's t-test and the Mann-Whitney test were used. P<0.05 was considered to indicate a statistically significant difference. Significantly worse prognosis in terms of overall survival (P=0.023) and progression-free survival (P=0.011) was detected in the CA125 ≥500 U/ml group of optimally cytoreduced patients compared with in the CA125 <500 U/ml group. The complete cytoreduction rate was higher in CA125 <500 U/ml (33.9%) vs. CA125 ≥500 U/ml (21.6%). A CA125 level >1,404 U/ml had a higher rate of suboptimal cytoreduction (32.4%) compared with lower CA125 levels. A pretreatment CA125 level ≥500 U/ml had significantly worse prognostic impact after optimal cytoreduction compared with CA125 <500 U/ml. The higher the CA125 level the higher the suboptimal cytoreduction rate. Patients with CA125 ≥500 U/ml may be candidates for an initial laparoscopic approach to specify resectability and to determine how to proceed. Overall, CA125 levels appear to be helpful in predicting suboptimal cytoreductive surgery for patients with primary ovarian cancer, but should be interpreted together with clinical and radiologic findings. This may improve defining the optimal treatment strategy in these patients.

Perioperative strategy and outcome in giant retroperitoneal dedifferentiated liposarcoma-results of a retrospective cohort study.

BACKGROUND AND OBJECTIVES: Retroperitoneal liposarcoma (RPLS) are common soft tissue sarcomas of adulthood. The aim of this study is to show resectability of even giant liposarcomas and to identify factors associated with recurrence and survival in primary retroperitoneal liposarcomas. METHODS: We retrospectively reviewed the records of patients with retroperitoneal liposarcoma. Seventy-seven patients met inclusion criteria. Out of these 10 patients with primary giant, dedifferentiated retroperitoneal liposarcomas were operated with en bloc compartment resection with intention of radical resection. Treatment consisted of neoadjuvant radiochemotherapy and surgical resection or surgical resection. RESULTS: In 6 patients, neoadjuvant radiochemotherapy was performed; 3 patients were treated with surgical resection alone and 1 patient received adjuvant chemotherapy. The median diameter of tumor size was 360 mm (300 to 440 mm). Operative outcome showed complete resection in all 10 patients. Local tumor free survival was in median 19 month. Tumor recurrence was seen in 3 of 4 patients (75%) without neoadjuvant radiochemotherapy, and in 2 of 6 patients (33%) after neoadjuvant radiochemotherapy in 2 years follow-up. CONCLUSION: Even in case of giant retroperitoneal liposarcoma, complete resection is possible and remains the principal treatment. The rate of recurrence was improved in patients with neoadjuvant radiochemotherapy.

Associated abdominal injuries do not influence quality of care in pelvic fractures-a multicenter cohort study from the German Pelvic Registry.

Background: Pelvic fractures are rare but serious injuries. The influence of a concomitant abdominal trauma on the time point of surgery and the quality of care regarding quality of reduction or the clinical course in pelvic injuries has not been investigated yet. Methods: We retrospectively analyzed the prospective consecutive cohort from the multicenter German Pelvic Registry of the German Trauma Society in the years 2003-2017. Demographic, clinical, and operative parameters were recorded and compared for two groups (isolated pelvic fracture vs. combined abdominal/pelvic trauma). Results: 16.359 patients with pelvic injuries were treated during this period. 21.6% had a concomitant abdominal trauma. The mean age was 61.4 ± 23.5 years. Comparing the two groups, patients with a combination of pelvic and abdominal trauma were significantly younger (47.3 ± 22.0 vs. 70.5 ± 20.4 years; p < 0.001). Both, complication (21.9% vs. 9.9%; p < 0.001) and mortality (8.0% vs. 1.9%; p < 0.001) rates, were significantly higher.In the subgroup of acetabular fractures, the operation time was significantly longer in the group with the combined injury (198 ± 104 vs. 176 ± 81 min, p = 0.001). The grade of successful anatomic reduction of the acetabular fracture did not differ between the two groups. Conclusion: Patients with a pelvic injury have a concomitant abdominal trauma in about 20% of the cases. The clinical course is significantly prolonged in patients with a combined injury, with increased rates of morbidity and mortality. However, the quality of the reduction in the subgroup of acetabular fractures is not influenced by a concomitant abdominal injury. Trial registration: ClinicalTrials.gov, NCT03952026, Registered 16 May 2019, retrospectively registered.

[Quality of operative treatment of pelvic fractures is not influenced by an additional abdominal injury : A monocentric registry study]. / Die Qualität der operativen Versorgung von Beckenfrakturen wird durch eine zusätzliche Abdominalverletzung nicht beeinflusst : Eine monozentrische Registerstudie.

BACKGROUND: Pelvic fractures are rare but severe injuries. The influence of a concomitant abdominal trauma on the quality of care regarding operative parameters, such as reduction quality and the clinical course in pelvic injuries has not yet been sufficiently investigated. METHODS: This study retrospectively analyzed the prospective consecutive data of patients with pelvic injuries treated at the BG Trauma Center in Tübingen in the years 2003-2017. Demographic, clinical and operative parameters were recorded and compared between two groups (isolated pelvic fracture vs. combined abdominal/pelvic trauma). RESULTS: A total of 1848 patients with pelvic injuries were treated during this period and 18.6% had a concomitant abdominal trauma. The mean age was 62.3 ± 23.1 years. Comparing the two groups, patients with a combination of pelvic and abdominal trauma were significantly younger (46.3 ± 20.3 years vs. 70.6 ± 20.8 years; p < 0.001). Both the overall complication rate (31.2% vs. 9.4%; p < 0.001) and mortality (5.0% vs. 1.7%; p = 0.001) were significantly higher in the group with a combination of injuries. The time until definitive surgery of the pelvis was significantly longer in the group with combined injuries (6.0 ± 6.4 days vs. 4.5 ± 4.4 days; p = 0.002). The results of postoperative reduction did not differ between the two groups. CONCLUSION: Patients with a pelvic injuries have a concomitant abdominal trauma in approximately 20% of the cases. The clinical course is significantly prolonged in patients with a combined injury and morbidity and mortality rates are increased; however, the quality of the postoperative results is not influenced by a concomitant abdominal injury.

A Non-interventional Clinical Trial Assessing Immune Responses After Radiofrequency Ablation of Liver Metastases From Colorectal Cancer.

Background: Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous in situ tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells. This may explain a phenomenon termed abscopal effect, namely tumor regression in untreated lesions evidenced after distant thermal ablation or irradiation. In this study, we therefore assessed systemic and local immune responses in individual patients treated with RFA. Methods: For this prospective clinical trial, patients with liver metastasis from colorectal carcinoma (mCRC) receiving RFA and undergoing metachronous liver surgery for another lesion were recruited (n = 9) during a 5-year period. Tumor and non-malignant liver tissue samples from six patients were investigated by whole transcriptome sequencing and tandem-mass spectrometry, characterizing naturally presented HLA ligands. Tumor antigen-derived HLA-restricted peptides were selected by different predefined approaches. Further, candidate HLA ligands were manually curated. Peripheral blood mononuclear cells were stimulated in vitro with epitope candidate peptides, and functional T cell responses were assessed by intracellular cytokine staining. Immunohistochemical markers were additionally investigated in surgically resected mCRC from patients treated with (n = 9) or without RFA (n = 7). Results: In all six investigated patients, either induced immune responses and/or pre-existing T cell immunity against the selected targets were observed. Multi-cytokine responses were inter alia directed against known tumor antigens such as cyclin D1 but also against a (predicted) mutation contained in ERBB3. Immunohistochemistry did not show a relevant influx of immune cells into distant malignant lesions after RFA treatment (n = 9) as compared to the surgery only mCRC group (n = 7). Conclusions: Using an individualized approach for target selection, RFA induced and/or boosted T cell responses specific for individual tumor antigens were more frequently detectable as compared to previously published observations with well-characterized tumor antigens. However, the witnessed modest RFA-induced immunological effects alone may not be sufficient for the rejection of established tumors. Therefore, these findings warrant further clinical investigation including the assessment of RFA combination therapies e.g., with immune stimulatory agents, cancer vaccination, and/or immune checkpoint inhibitors.

Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity.

Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards 'normal' liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.