Enhancing drug therapy in ostomy patients: Best practice recommendations for medication management.

BACKGROUND: Ostomy surgery is a common procedure that poses various challenges for patients and healthcare professionals. There are numerous guidelines addressing different ostomy-related problems (ORPs) and supporting an interdisciplinary approach for ostomy care, but evidence-based literature for optimizing drug therapy after ostomy surgery is lacking. AIM: To investigate and characterize typical ORPs in relation to drug therapy and provide best practice recommendations from a pharmaceutical point of view. METHODS: Patients with an ileo- or colostomy were consecutively enrolled in a prospective, interventional monocentric cohort study during hospitalization, with particular attention to medication. A clinical pharmacist assessed DRPs by performing level 3 medication reviews and patient interviews. Pharmacists' interventions (PIs) were evaluated by two senior clinical pharmacists and documented in DokuPIK (Documentation of Pharmacists' Interventions in the Hospital). Following interdisciplinary discussions, physicians either accepted or rejected the proposed changes in drug therapy. Comparisons were made between ileostomy and colostomy patients regarding type and extent of PIs. RESULTS: Out of the 80 patients included in the cohort, 54 (67.5%) had an ileostomy and 26 (32.5%) a colostomy. In this study, 288 PIs were documented (234 ileostomy vs. 54 colostomy), of wich 94.0% were accepted and implemented by the physicians. The most common reason for PIs in both subgroups (29.6% ileostomy vs. 26.1% colostomy) was a missing drug although indicated (e.g. no loperamide, but high stoma output). The proportion of PIs associated with the ostomy was higher in ileostomy patients (48.3% ileostomy vs. 31.5% colostomy; p = 0.025). Typical ORPs were extracted and analyzed as case studies including recommendations for their respective management and prevention. CONCLUSION: This study highlights the importance of clinical pharmacists being a part of interdisciplinary teams to collaboratively improve ostomy care and patient safety. Especially ileostomy patients are more vulnerable for ORPs in the context of drug therapy and need to be monitored carefully.

Risk Factor Analysis for Developing Major Complications Following Esophageal Surgery-A Two-Center Study.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. METHODS: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. RESULTS: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). CONCLUSIONS: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies.

Obesity and diabetes mellitus are associated with SARS-CoV-2 outcomes without influencing signature genes of extrapulmonary immune compartments at the RNA level.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for eliciting Coronavirus disease 2019 (COVID-19) still challenges healthcare services worldwide. While many patients only suffer from mild symptoms, patients with some pre-existing medical conditions are at a higher risk for a detrimental course of disease. However, the underlying mechanisms determining disease course are only partially understood. One key factor influencing disease severity is described to be immune-mediated. In this report, we describe a post-mortem analysis of 45 individuals who died from SARS-CoV-2 infection. We could show that although sociodemographic factors and premedical conditions such as obesity and diabetes mellitus reduced survival time in our cohort, they were not associated with changes in the expression of immune-related signature genes at the RNA level in the blood, the gut, or the liver between these different groups. Our data indicate that obesity and diabetes mellitus influence SARS-CoV-2-related mortality, without influencing the extrapulmonary gene expression of immunity-related signature genes at the RNA level.

Preoperative TIPS and in-hospital mortality in patients with cirrhosis undergoing surgery.

Background & Aims: Cirrhosis is associated with an increased surgical morbidity and mortality. Portal hypertension and the surgery type have been established as critical determinants of postoperative outcome. We aim to evaluate the hypothesis that preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis is associated with a lower incidence of in-house mortality/liver transplantation (LT) after surgery. Methods: A retrospective database search for the years 2010-2020 was carried out. We identified 64 patients with cirrhosis who underwent surgery within 3 months after TIPS placement and 131 patients with cirrhosis who underwent surgery without it (controls). Operations were categorised into low-risk and high-risk procedures. The primary endpoint was in-house mortality/LT. We analysed the influence of high-risk surgery, preoperative TIPS placement, age, sex, baseline creatinine, presence of ascites, Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD), American Society of Anesthesiologists (ASA), and model for end-stage liver disease (MELD) scores on in-house mortality/LT by multivariable Cox proportional hazards regression. Results: In both the TIPS and the control cohort, most patients presented with a Child-Pugh B stage (37/64, 58% vs. 70/131, 53%) at the time of surgery, but the median MELD score was higher in the TIPS cohort (14 vs. 11 points). Low-risk and high-risk procedures amounted to 47% and 53% in both cohorts. The incidence of in-house mortality/LT was lower in the TIPS cohort (12/64, 19% vs. 52/131, 40%), also when further subdivided into low-risk (0/30, 0% vs. 10/61, 16%) and high-risk surgery (12/34, 35% vs. 42/70, 60%). Preoperative TIPS placement was associated with a lower rate for postoperative in-house mortality/LT (hazard ratio 0.44, 95% CI 0.19-1.00) on multivariable analysis. Conclusions: A preoperative TIPS might be associated with reduced postoperative in-house mortality in selected patients with cirrhosis. Impact and implications: Patients with cirrhosis are at risk for more complications and a higher mortality after surgical procedures. A transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis, but it is unclear if it also helps to lower the risk of surgery. This study takes a look at complications and mortality of patients undergoing surgery with or without a TIPS, and we found that patients with a TIPS develop less complications and have an improved survival. Therefore, a preoperative TIPS should be considered in selected patients, especially if indicated by ascites.

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Endoscopic negative-pressure treatment : From management of complications to pre-emptive active reflux drainage in abdomino-thoracic esophageal resection-A new safety concept for esophageal surgery.

INTRODUCTION: Early postoperative reflux (PR) can compromise anastomotic healing after Ivor Lewis esophagectomy (ILE) and poses a risk for aspiration. Anastomotic insufficiency is the most threatening surgical complication. We present the protective method of pre-emptive active reflux drainage (PARD) with simultaneous enteral feeding. We report our experience with this new safety concept in esophageal surgery in a cohort of 43 patients. MATERIALS AND METHODS: For PARD we use a double lumen open porous film drainage (dOFD). To create the dOFD, the gastric tube of a Trelumina probe (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore drainage film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over a length of 25 cm. The dOFD is endoscopically inserted into the tubular stomach intraoperatively after completion of the anastomosis. Continuous negative pressure is applied with an electronic pump (-125 mm Hg). The PR is continuously aspirated completely and the stomach and anastomotic region are decompressed. At the same time, nutrition is delivered via an integrated intestinal tube. Depending on the results of the endoscopic control after 5 days, PARD is either continued or terminated. RESULTS: During the observation period (2017-2023), PARD was used in all patients (n = 43) with ILE. The healing rate under PARD was 100% and healing was observed in all anastomoses. No additional endoscopic procedures or surgical revisions of the anastomoses were required. The median duration of PARD was 8 days (range 4-21). We observed problems in the healing of the anastomosis in 20 of 43 patients (47%) for whom we defined endoscopic criteria for at-risk anastomosis. CONCLUSIONS: Our results suggest that PARD has a strong protective effect on anastomotic healing and may reduce the risk of anastomotic insufficiency. The integrated feeding tube of the dOFD allows early postoperative enteral feeding while simultaneously applying negative pressure. PARD appears to prevent the negative consequences of impaired anastomotic healing.

[Endoscopic negative pressure treatment : From management of complications to pre-emptive active reflux drainage in abdominothoracic esophageal resection-A new safety concept for esophageal surgery]. / Endoskopische Unterdrucktherapie : Vom Komplikationsmanagement zur präemptiven aktiven Refluxdrainage bei abdomino-thorakaler Ösophagusresektion ­ ein neues Sicherheitskonzept für die Ösophaguschirurgie.

INTRODUCTION: Early postoperative reflux (PR) can compromise anastomotic healing after Ivor Lewis esophagectomy (ILE) and poses a risk for aspiration. Anastomotic insufficiency is the most threatening surgical complication. We present the protective method of pre-emptive active reflux drainage (PARD) with simultaneous enteral feeding. We report our experience with this new safety concept in esophageal surgery in a cohort of 43 patients. MATERIALS AND METHODS: For PARD we use a double lumen open porous film drainage (dOFD). To create the dOFD, the gastric tube of a Trelumina probe (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore drainage film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over a length of 25 cm. The dOFD is endoscopically inserted into the tubular stomach intraoperatively after completion of the anastomosis. Continuous negative pressure is applied with an electronic pump (-125 mm Hg). The PR is continuously aspirated completely and the stomach and anastomotic region are decompressed. At the same time, nutrition is delivered via an integrated intestinal tube. Depending on the results of the endoscopic control after 5 days, PARD is either continued or terminated. RESULTS: During the observation period (2017-2023), PARD was used in all patients (n = 43) with ILE. The healing rate under PARD was 100% and healing was observed in all anastomoses. No additional endoscopic procedures or surgical revisions of the anastomoses were required. The median duration of PARD was 8 days (range 4-21). We observed problems in the healing of the anastomosis in 20 of 43 patients (47%) for whom we defined endoscopic criteria for at-risk anastomosis. CONCLUSIONS: Our results suggest that PARD has a strong protective effect on anastomotic healing and may reduce the risk of anastomotic insufficiency. The integrated feeding tube of the dOFD allows early postoperative enteral feeding while simultaneously applying negative pressure. PARD appears to prevent the negative consequences of impaired anastomotic healing.

Robotic-assisted repair of incisional hernia-early experiences of a university robotic hernia program and comparison with open and minimally invasive sublay technique (eMILOS).

PURPOSE: With robotic surgical devices, an innovative tool has stepped into the arena of minimally invasive hernia surgery. It combines the advantages of open (low recurrence rates and ability to perform complex procedure such as transverse abdominis release) and laparoscopic surgery (low rate of wound and mesh infections, less pain). However, a superiority to standard minimally invasive procedures has not yet been proven. We present our first experiences of robotic mesh repair of incisional hernias and a comparison of our results with open and minimally invasive sublay techniques. METHODS: A retrospective analysis of all patients who underwent robotic-assisted mesh repair (RAHR) for incisional hernia between April and November 2022 (RAHR group) and patients who underwent open sublay (Sublay group) or eMILOS hernia repair (eMILOS group) between January 2018 and November 2022 was carried out. Patients in the RAHR group were matched 1:2 to patients in the Sublay group by propensity score matching. Patient demographics, preoperative hernia characteristics and cause of hernia, intraoperative variables, and postoperative outcomes were evaluated. Furthermore, a subgroup analysis of only midline hernia was performed. RESULTS: A total of 21 patients received robotic-assisted incisional hernia repair. Procedures performed included robotic retro-muscular hernia repair (r-RMHR, 76%), with transverse abdominis release in 56% of the cases. In one patient, r-RHMR was combined with robotic inguinal hernia repair. Two patients (10%) were operated with total extraperitoneal technique (eTEP). Robotic-assisted transabdominal preperitoneal hernia repair (r-TAPP) was performed in three patients (14%). Median (range) operating time in the RAHR group was significantly longer than in the sublay and eMILOS group (291 (122-311) vs. 109.5 (48-270) min vs. 123 (100-192) min, respectively, p < 0.001). The meshes applied in the RAHR group were significantly compared to the sublay (mean (SD) 529 ± 311 cm2 vs. 356 ± 231, p = 0.037), but without a difference compared to the eMILOS group (mean (SD) 596 ± 266 cm2). Median (range) length of hospital stay in the RAHR group was significantly shorter compared to the Sublay group (3 (2-7) vs. 5 (1-9) days, p = 0.032), but not significantly different to the eMILOS group. In short term follow-up, no hernia recurrence was observed in the RAHR and eMILOS group, with 9% in the Sublay group. The subgroup analysis of midline hernia revealed very similar results. CONCLUSION: Our data show a promising outcome after robotic-assisted incisional hernia repair, but no superiority compared to the eMILOS technique. However, RAHR is a promising technique especially for complex hernia in patients with relevant risk factors, especially immunosuppression. Longer follow-up times are needed to accurately assess recurrence rates, and large prospective trials are needed to show superiority of robotic compared to standard open and minimally invasive hernia repair.

Intestinal IL-1ß Plays a Role in Protecting against SARS-CoV-2 Infection.

The intestine is constantly balancing the maintenance of a homeostatic microbiome and the protection of the host against pathogens such as viruses. Many cytokines mediate protective inflammatory responses in the intestine, among them IL-1ß. IL-1ß is a proinflammatory cytokine typically activated upon specific danger signals sensed by the inflammasome. SARS-CoV-2 is capable of infecting multiple organs, including the intestinal tract. Severe cases of COVID-19 were shown to be associated with a dysregulated immune response, and blocking of proinflammatory pathways was demonstrated to improve patient survival. Indeed, anakinra, an Ab against the receptor of IL-1ß, has recently been approved to treat patients with severe COVID-19. However, the role of IL-1ß during intestinal SARS-CoV-2 infection has not yet been investigated. Here, we analyzed postmortem intestinal and blood samples from patients who died of COVID-19. We demonstrated that high levels of intestinal IL-1ß were associated with longer survival time and lower intestinal SARS-CoV-2 RNA loads. Concurrently, type I IFN expression positively correlated with IL-1ß levels in the intestine. Using human intestinal organoids, we showed that autocrine IL-1ß sustains RNA expression of IFN type I by the intestinal epithelial layer. These results outline a previously unrecognized key role of intestinal IL-1ß during SARS-CoV-2 infection.

Minimally invasive intrathoracic negative-pressure therapy and flexible thoracoscopy (FlexVATS) for patients with pleural empyema.

To determine whether a new surgical method using a flexible endoscope (FlexVATS) to perform sparing debridement and apply negative-pressure therapy without extensive decortication may be an alternative treatment option for empyema. Surgical treatment of pleural empyema is associated with considerable postoperative complications and mortality rates, and alternative treatment options are being explored to improve patient outcomes. This was a prospective case series. Seventeen consecutive patients treated with FlexVATS between February 2021 and August 2022 were included in the study. Only patients for whom FlexVATS was the first therapeutic intervention for pleural empyema were included. Treatment success, defined as infection resolution, was the primary endpoint of the study. The secondary endpoints were length of hospital stay, 90-day mortality, and empyema cavity volume reduction. Patients who had previously been treated for pleural empyema by either drainage or surgery were excluded. The trial was performed as a single-centre study at a tertiary medical centre in Germany. In total, 17 patients with pleural empyema were included in the study. The median (IQR) duration of vacuum treatment was 15 days (8-35 days). Twelve of the 17 (71%) patients were successfully treated, and a significant reduction in the empyema cavity volume was observed. 41% of the dressing changes were performed outside the operating room. Compared with a historic cohort of conventionally treated patients (decortication via VATS or thoracotomy), the 90-day mortality rates tended to be lower without reaching statistical significance. Three patients (18%) died in hospital during treatment. No negative pressure-therapy-related complications were observed. FlexVATS therapy is a promising alternative therapy for both healthy and debilitated patients with pleural empyema. Larger randomised trials are required to validate this treatment option.

Socioeconomic Deprivation Is Not Associated with Outcomes after Esophagectomy at a German High-Volume Center.

In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic deprivation may be related to postoperative complications and reduced overall survival. Therefore, 310 patients who had undergone esophagectomy for cancer in curative intent between 2012 and 2020 at the University Medical Center Hamburg-Eppendorf (UKE) were included in this study. Socioeconomic status (SES) was estimated using the purchasing power of patients' postal codes as a surrogate parameter. No association was found between SES and tumor stage or comorbidities at the time of surgery. Moreover, SES was neither associated with postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment outcomes.

Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies.

An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.

Challenges in the interdisciplinary treatment of leakages after left-sided colorectal surgery: endoscopic negative pressure therapy, open-pore film drainage therapy and beyond.

PURPOSE: The treatment of anastomotic leakage after left colorectal surgery remains challenging. Since its introduction, endoscopic negative pressure therapy (ENPT) has proven to be advantageous, reducing the necessity of surgical revision. The aim of our study is to present our experience with endoscopic treatment of colorectal leakages and to identify potential factors influencing treatment outcome. METHODS: Patients who underwent endoscopic treatment of colorectal leakage were retrospectively analyzed. Primary endpoint was the healing rate and success of endoscopic therapy. RESULTS: We identified 59 patients treated with ENPT between January 2009 and December 2019. The overall closure rate was 83%, whereas only 60% of the patients were successfully treated with ENPT and 23% needed further surgery. The time between diagnosis of leakage and uptake of endoscopic treatment did not influence the closure rate, but patients with chronic fistula (> 4 weeks) showed a significantly higher reoperation rate than those with an acute fistula (94% vs 6%, p = 0.01). CONCLUSION: ENPT is a successful treatment option for colorectal leakages, which appears to be more favorable when started early. Further studies are still needed to better describe its healing potential, but it deserves an integral role in the interdisciplinary treatment of anastomotic leakages.

TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.

Intrathoracic vacuum therapy for the therapy of pleural empyema-a systematic review and analysis of the literature.

Background: Pleural empyema is a serious and potentially deadly disease leading to a significant burden on health care systems. Conservative and surgical treatment results remain poor, with high morbidity and mortality rates. Patients with pleural empyema are often multimorbid and poor candidates for surgery. Therefore, it appears sensible to explore alternative, less invasive treatment options. Recently, the well-established vacuum sponge therapy has been adopted in the treatment of pleural infections. The goal of this systematic review was to identify the existing literature and reported results of vacuum therapy for pleural empyema. Methods: A systematic search of MEDLINE and the Cochrane Database was performed independently by two reviewers using predefined criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. In addition, abstracts from selected conference proceedings were screened and reference scanning of the search results was performed. Single case reports were excluded. Results: Fourteen studies met the selection criteria and were reviewed. A total of 165 patients were treated with vacuum therapy in the studies reviewed. 61.2% of the patients had pleural empyema secondary to thoracic surgery. In 71.5% of the patients, vacuum therapy was applied following open window thoracostomy (OWT). Mortality rates of 0-33% were reported for vacuum therapy after OWT and 0-9.3% for vacuum therapy without OWT. Length of hospital stay (LOHS) ranged from 44-217 days for patients after OWT and could not be analysed for vacuum therapy without OWT due to lacking data. Median treatment time was 7-14 days. Treatment related complications were rare overall. Success rates defined as infection resolution were high irrespective of previous treatment and cause of empyema. Conclusions: The current literature shows that pleural vacuum therapy is a promising, safe, and feasible treatment alternative to existing treatment modalities for pleural empyema. However, the evidence for vacuum therapy without OWT is poor, and further data, optimally prospective or randomised control trials comparing the conventional surgical approach of video-assisted thoracoscopic surgery (VATS) decortication and minimally invasive vacuum therapy, are needed.

Decreased expression of prolyl hydroxylase 1 is associated with poor prognosis in colorectal cancers.

BACKGROUND: Prolyl hydroxylase 1 (PHD1) is a prognostic marker in several cancers. AIMS AND SCOPES: This study was undertaken to elucidate the clinical relevance of PHD1 in colorectal cancer (CRC) prognosis. MATERIALS AND METHODS: We compared PHD1 expression on a tissue microarray (TMA) containing samples from 1800 CRCs with corresponding clinicopathological tumor variables and patient survival. RESULTS: While PHD1 staining was always high in benign colorectal epithelium, high PHD1 staining was detectable in only 71.8% of CRCs. Low PHD1 staining was associated with advanced tumor stage (p = 0.0101) and shortened overall survival in CRC patients (p = 0.0011). In a multivariable analysis including tumor stage, histological type and PHD1 staining revealed tumor stage and histological type (p < 0.0001 each), but also PHD1 staining (p = 0.0202) to be independent prognostic markers for CRC. CONCLUSIONS: In our cohort, loss of PHD1 expression independently identified a subset of CRC patients with poor overall survival and might, thus, be a promising prognostic marker. PHD1 targeting may even allow for specific therapeutic approaches for these patients.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.

PURPOSE: Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). METHODS: RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. RESULTS: While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915). CONCLUSION: Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.

Bitter taste receptors (T2Rs) are G protein­coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra­oral cells eliciting non­gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor­derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti­migratory and chemosensitizing effects to 5­fluoruracil (5­FU) and to 5­FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.