Künstliche-Intelligenz-Tools sind das Hype-Thema der Stunde und bereits im Alltag vieler Menschen angekommen. Auch in der Medizin gibt es rasante Entwicklungen im technischen Innovationsbereich mit dem Potenzial, den Arbeitsalltag auch von Chirurginnen und Chirurgen grundlegend zu verändern. Zahlreiche Anwendungsmöglichkeiten, die bis vor Kurzem noch undenkbar waren, versprechen eine Verbesserung der Patientenversorgung bei effizienterer Nutzung der zur Verfügung stehenden Ressourcen. Allerdings gibt es bisher kaum klinisch eingesetzte und klinisch relevante KI-Tools. Zudem existieren auch ethische und medizinrechtliche Bedenken. Die robotische Chirurgie setzt sich inzwischen hingegen im klinischen Alltag durch und bietet eine sehr gute Plattform für den Einsatz digitaler Anwendungen inkl. KI. Inwieweit können Roboter und KI die chirurgische Arbeit tatsächlich verbessern? Welche Potenziale liegen in den zurzeit verfolgten Innovationsprojekten und wo liegen die aktuellen Grenzen?

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.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundProlyl hydroxylase 1 (PHD1) is a prognostic marker in several cancers.Aims and scopesThis study was undertaken to elucidate the clinical relevance of PHD1 in colorectal cancer (CRC) prognosis.Materials and methodsWe compared PHD1 expression on a tissue microarray (TMA) containing samples from 1800 CRCs with corresponding clinicopathological tumor variables and patient survival.ResultsWhile 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.ConclusionsIn 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.

The role of CD10 expression in colorectal cancer has been controversially discussed in the literature. Some data suggest a predictive capacity for lymph node and liver metastases, thus influencing overall survival (OS) and disease-free survival (DFS). This study aims to analyse the relationship between CD10 expression and overall survival (OS) in a European cohort. To determine the association of CD10 expression with tumour phenotype, molecular features, and prognosis, a tissue microarray of 1469 colorectal carcinomas was analysed using immunohistochemistry and was compared with matched clinicopathologic data. CD10 expression correlated with earlier tumour stages (p = 0.017) and left-sided colon cancer (p < 0.001). However, no correlation was found between CD10 expression and lymph node involvement (p = 0.711), tumour grading (p = 0.397), or overall survival (p = 0.562). Even in the subgroup analysis of tumour or nodal stage, CD10 did not affect overall survival, although it was significantly associated with p53 and nuclear β-catenin expression (p = 0.013 and p < 0.001, respectively). CD10 expression correlates with earlier tumour stages, colon cancer location, and indicators of aggressive CRC subtypes. However, we can exclude CD10 as a relevant independent prognosticator for CRC.

Neben der erhofften Verbesserung des Behandlungsergebnisses durch gesetzliche Mindestmengen und Zertifizierungen der onkologischen Viszeralchirurgie sind auch negative Effekte für Patienten und Behandler zu erwarten. Vor diesem Hintergrund soll in diesem Beitrag die Evidenzlage von Mindestmengen und Zertifizierungen in der Pankreas-, Ösophagus- und Kolorektalchirurgie dargestellt und anschließend auf Kritikpunkte an der zunehmenden Zentrumsbildung und Lösungsansätze eingegangen werden.

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.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of de novo mTOR inhibitor‐based versus calcineurin inhibitor‐based immunosuppression for liver transplant recipients.

Background:The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown.Methods:We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages.Results:Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice.Conclusions:We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.

Fragestellung Patienten mit Leberzirrhose weisen eine erhöhte postoperative Mortalität auf. Ob die Senkung der portalen Hypertension durch eine TIPS-Anlage einen Effekt auf das postoperative Outcome hat, ist unklar.

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.

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.

Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4+ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1flox/flox × AlbCre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22–IL-22BP axis in HCC.

Background Concomitant liver cirrhosis is a crucial risk factor for major surgeries. However, only few data are available concerning cirrhotic patients requiring esophagectomy for malignant disease. Methods From a prospectively maintained database of esophageal cancer patients, who underwent curative esophagectomy between 01/2012 and 01/2016, patients with concomitant liver cirrhosis (liver-cirrhotic patients, LCP) were compared to non-liver-cirrhotic patients (NLCP). Results Of 170 patients, 14 cirrhotic patients with predominately low MELD scores (≤ 9, 64.3%) were identified. Perioperative outcome was significantly worse for LCP, as proofed by 30-day (57.1% vs. 7.7, p<0.001) and 90-day mortality (64.3% vs. 9.6%, p<0.001), anastomotic leakage rate (64.3 vs. 22.3%, p = 0.002) and sepsis (57.1 vs. 21.5%, p = 0.006). Even after adjustment for age, gender, comorbidities, and surgical approach, LCP revealed higher odds for 30-day and 90-day mortality compared to NLCP. Moreover, 5-year survival analysis showed a significantly poorer long-term outcome of LCP (p = 0.023). For risk stratification, none of the common cirrhosis scores proved prognostic impact, whereas components as Bilirubin (auROC 94.4%), INR (auROC = 90.0%), and preoperative ascites (p = 0.038) correlated significantly with the perioperative outcome. Conclusion Curative esophagectomy for cirrhotic patients is associated with a dismal prognosis and should be evaluated critically. While MELD and Child score failed to predict perioperative mortality, Bilirubin and INR proofed excellent prognostic capacity in this cohort.

Introduction The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world. Methods To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data. Results CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth ( p = 0.015) and differentiation ( p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer. Conclusion Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.

Respiratory–digestive tract fistulas are fatal complications that occur in esophageal cancer treatment. Interdisciplinary treatment strategies are still evolving, especially in anatomical treatment stratification. Thus, this study aims to evaluate general therapeutic strategies for this rare condition. Medical records were reviewed for esophageal cancer-associated respiratory–digestive tract fistula patients treated between January 2008 and September 2021. Fistulas were classified according to being surgery- and tumor-associated. Treatment strategies, clinical success, and survival were analyzed. A total of 51 patients were identified: 28 had tumor-associated fistulas and 23 surgery-associated fistulas. Risk factors for fistula development such as radiation (OR = 0.290, p = 0.64) or stent implantation (OR = 1.917, p = 0.84) did not correlate with lack of symptom control for RDF patients. In contrast, advanced lymph node metastasis as another risk factor was associated with persistent symptoms after treatment for RDF patients (OR = 0.611, p = 0.01). Clinical success significantly correlated with bilateral fistula repair in surgery-associated fistulas (p = 0.01), while tumor-associated fistulas benefited the most from non-surgical (p = 0.04) or combined surgical and non-surgical intervention (p = 0.04) and a bilateral fistula repair (p = 0.02) in terms of overall survival. The therapeutic strategy should aim for bilateral fistula closure. A multidisciplinary, stepwise approach might have the best chance for restoration or symptom control with optimized overall survival in selected patients.

Purpose To define the best possible outcomes for robotic-assisted low anterior rectum resection (RLAR) using total mesorectal excision (TME) in low-morbid patients, performed by expert robotic surgeons in German robotic centers. The benchmark values were derived from these results. Methods The data was retrospectively collected from five German expert centers. After patient exclusion (prior surgery, extended surgery, no prior anastomosis, hand-sewn anastomosis), the benchmark cohort was defined (n = 226). The median with interquartile range was first calculated for the individual centers. The 75th percentile of the median results was defined as the benchmark cutoff and represents the “perfect” achievable outcome. This applied to all benchmark values apart from lymph node yield, where the cutoff was defined as the 25th percentile (more lymph nodes are better). Results The benchmark values for conversion and intraoperative complication rates were ≤ 4.0% and ≤ 1.4%, respectively. For postoperative complications, the benchmark was ≤ 28% for “any” and ≤ 18.0% for major complications. The R0 and complete TME rate benchmarks were both 100%, with a lymph node yield of > 18. The benchmark for rate of anastomotic insufficiency was < 12.5% and 90-day mortality was 0%. Readmission rates should not exceed 4%. Conclusion This outcome analysis of patients with low comorbidity undergoing RLAR may serve as a reference to evaluate surgical performance in robotic rectum resection.

Improved long-term survival after low anterior resection (LAR) for rectal cancer highlights the importance of functional outcome. Urogenital and anorectal dysfunction is frequently reported after conventional LAR. Advanced minimally invasive techniques such as robotic (RoTME) and transanal total mesorectal excision (TaTME) might improve functional results by precisely dissecting and preserving autonomic nerves. We compared functional outcomes after RoTME or TaTME in a multicenter study. One hundred twenty patients (55 RoTME/65 TaTME) were prospectively included in four participating centers. Anorectal (Wexner and low anterior resection syndrome (LARS) Score), urinary (International Consultation on Incontinence—Male/Female Lower Urinary Tract Symptoms Score (ICIQ-MLUTS/ICIQ-FLUTS) and International Prostate Symptom Scale (IPSS)), and sexual (International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI)) outcomes at 12 months after surgery were compared to preoperative scores. The response rate to the 1-year postoperative functional assessment by questionnaire was 79.5%. RoTME enabled better anorectal function compared to TaTME (LARS score 4.3 ± 2.2 vs. 9.8 ± 1.5, p = 0.038, respectively). TaTME proved superior at preserving male urinary function, while female urinary function was comparable in both groups, with only mild postoperative impairment (RoTME vs. TaTME, respectively: ICIQ-MLUTS 13.8 ± 4.9 vs. 1.8 ± 5.8, p = 0.038; ICIQ-FLUTS Incontinence Score − 0.3 ± 1.0 vs. − 0.2 ± 0.9, p = 0.844). Both techniques demonstrated comparable male (RoTME − 13.4 ± 2.7 vs. TaTME − 11.7 ± 3.4, p = 0.615) and female (RoTME 5.2 ± 4.6 vs. TaTME 10.5 ± 6.4, p = 0.254) sexual function. After adjustment for risk factors, RoTME provided better anorectal functional results, whereas TaTME was better at preserving male urinary function. Overall, both techniques demonstrated only mild postoperative functional impairment.

BACKGROUND:Improving survival rates in rectal cancer patients has generated a growing interest in functional outcomes after total mesorectal excision (TME). The well-established low anterior resection syndrome (LARS) score assesses postoperative anorectal impairment after TME. Our meta-analysis is the first to compare bowel function after open, laparoscopic, transanal, and robotic TME. METHODS:All studies reporting functional outcomes after rectal cancer surgery (LARS score) were included, and were compared with a consecutive series of robotic TME (n = 48). RESULTS:Thirty-two publications were identified, including 5 565 patients. Anorectal function recovered significantly better within one year after robotic TME (3.8 [95%CI -9.709-17.309]) versus laparoscopic TME (26.4 [95%CI 19.524-33.286]), p = 0.006), open TME (26.0 [95%CI 24.338-29.702], p = 0.002) and transanal TME (27.9 [95%CI 22.127-33.669], p = 0.003). CONCLUSIONS:Robotic TME enables better recovery of anorectal function compared to other techniques. Further prospective, high-quality studies are needed to confirm the benefits of robotic surgery.