Publications by authors named "Christiane Bruns"

330 Publications

Molekulare Prognosefaktoren in der onkologischen Viszeralchirurgie.

Zentralbl Chir 2022 Aug 16;147(4):333-337. Epub 2022 Aug 16.

Klinik für Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie, Universitätsklinik Köln, Köln.

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http://dx.doi.org/10.1055/a-1864-2538DOI Listing
August 2022

Multicentric exploration of tool annotation in robotic surgery: lessons learned when starting a surgical artificial intelligence project.

Surg Endosc 2022 Aug 8. Epub 2022 Aug 8.

Robotic Innovation Laboratory, Department of General, Visceral, Tumor and Transplantsurgery, University Hospital Cologne, Cologne, Germany.

Background: Artificial intelligence (AI) holds tremendous potential to reduce surgical risks and improve surgical assessment. Machine learning, a subfield of AI, can be used to analyze surgical video and imaging data. Manual annotations provide veracity about the desired target features. Yet, methodological annotation explorations are limited to date. Here, we provide an exploratory analysis of the requirements and methods of instrument annotation in a multi-institutional team from two specialized AI centers and compile our lessons learned.

Methods: We developed a bottom-up approach for team annotation of robotic instruments in robot-assisted partial nephrectomy (RAPN), which was subsequently validated in robot-assisted minimally invasive esophagectomy (RAMIE). Furthermore, instrument annotation methods were evaluated for their use in Machine Learning algorithms. Overall, we evaluated the efficiency and transferability of the proposed team approach and quantified performance metrics (e.g., time per frame required for each annotation modality) between RAPN and RAMIE.

Results: We found a 0.05 Hz image sampling frequency to be adequate for instrument annotation. The bottom-up approach in annotation training and management resulted in accurate annotations and demonstrated efficiency in annotating large datasets. The proposed annotation methodology was transferrable between both RAPN and RAMIE. The average annotation time for RAPN pixel annotation ranged from 4.49 to 12.6 min per image; for vector annotation, we denote 2.92 min per image. Similar annotation times were found for RAMIE. Lastly, we elaborate on common pitfalls encountered throughout the annotation process.

Conclusions: We propose a successful bottom-up approach for annotator team composition, applicable to any surgical annotation project. Our results set the foundation to start AI projects for instrument detection, segmentation, and pose estimation. Due to the immense annotation burden resulting from spatial instrumental annotation, further analysis into sampling frequency and annotation detail needs to be conducted.
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http://dx.doi.org/10.1007/s00464-022-09487-1DOI Listing
August 2022

[ICG lymph node mapping in cancer surgery of the upper gastrointestinal tract].

Chirurgie (Heidelb) 2022 Jun 3. Epub 2022 Jun 3.

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln (AöR), Kerpener Str. 62, 50937, Köln, Deutschland.

The importance of the assessment of the N‑status in gastric carcinoma, tumors of the gastroesophageal junction and esophageal cancer is undisputed; however, there is currently no internationally validated method for lymph node mapping in esophageal and gastric cancer. Near-infrared fluorescence imaging (NIR) is an innovative technique from the field of vibrational spectroscopy, which in combination with the fluorescent dye indocyanine green (ICG) enables intraoperative real-time visualization of anatomical structures. The ICG currently has four fields of application in oncological surgery: intraoperative real-time angiography for visualization of perfusion, lymphography for visualization of lymphatic vessels, visualization of solid tumors, and (sentinel) lymph node mapping. For imaging of the lymph drainage area and therefore the consecutive lymph nodes, peritumoral injection of ICG must be performed. Several studies have demonstrated the feasibility of peritumoral injection of ICG administered 15 min to 3 days preoperatively with subsequent intraoperative visualization of the lymph nodes. So far prospective randomized studies on the validation of the method are still lacking. In contrast, the use of ICG for lymph node mapping and visualization of sentinel lymph nodes in gastric cancer has been performed in large cohorts as well as in prospective randomized settings. Up to now, multicenter studies for ICG-guided lymph node mapping during oncological surgery of the upper gastrointestinal tract are lacking. Artificial intelligence methods can help to evaluate these techniques in an automated manner in the future as well as to support intraoperative decision making and therefore to improve the quality of oncological surgery.
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http://dx.doi.org/10.1007/s00104-022-01659-yDOI Listing
June 2022

[Modern molecular and imaging diagnostics in pancreatic neuroendocrine neoplasms].

Chirurgie (Heidelb) 2022 Aug 25;93(8):731-738. Epub 2022 May 25.

Klinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln, Kerpenerstr. 62, 50937, Köln, Deutschland.

Background And Objective: New molecular diagnostic and radiologic imaging techniques can be used to assess the extent, risk of recurrence, prognosis and response to treatment of pancreatic neuroendocrine neoplasms (pNENs). They therefore represent a decisive help in setting the indications for surgical treatment, especially in advanced stages.

Methods: This article presents a narrative assessment of the options and evidence for modern molecular and radiologic imaging diagnostics of pNENs based on the current literature.

Results: While circulating DNA, circulating tumor cells and microRNAs have not yet become established in everyday clinical practice, the current literature suggests a promising role for the so-called NETest. Recent studies demonstrated its possible importance for the surgical management of pNENs. Besides [68Ga]Ga-DOTA-SSA-PET and [18]FDG-PET, which remain the gold standards for imaging NENs, radiomics represent an exciting alternative to biopsies and will possibly play an increasingly important role in the future.

Discussion: There are new promising alternatives to chromogranin A, which has been clinically widespread since the 1970s despite several drawbacks, to map the extent, risk of recurrence, prognosis and response to treatment of pancreatic pNENs. In terms of personalized medicine, modern molecular and radiological diagnostics should play an increasing role for indicating and planning surgical treatment and for follow-up in the future.
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http://dx.doi.org/10.1007/s00104-022-01645-4DOI Listing
August 2022

Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial.

Front Oncol 2022 13;12:917961. Epub 2022 Jul 13.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.

Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04460352.
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http://dx.doi.org/10.3389/fonc.2022.917961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326032PMC
July 2022

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

Gut 2022 Jul 26. Epub 2022 Jul 26.

Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.

Objective: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling.

Design: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis.

Results: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models.

Conclusion: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.
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http://dx.doi.org/10.1136/gutjnl-2021-326698DOI Listing
July 2022

Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion.

J Vis Exp 2022 07 6(185). Epub 2022 Jul 6.

Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne;

The lack of suitable translational research models reflecting primary disease to explore tumorigenesis and therapeutic strategies is a major obstacle in esophageal adenocarcinoma (EAC). Patient-derived organoids (PDOs) have recently emerged as a remarkable preclinical model in a variety of cancers. However, there are still limited protocols available for developing EAC PDOs. Once the PDOs are established, the propagation and cryopreservation are essential for further downstream analyses. Here, two different methods have been standardized for EAC PDOs subculture and cryopreservation, i.e., with and without single cell digestion. Both methods can reliably obtain appropriate cell viability and are applicable for a diverse experimental setup. The current study demonstrated that subculturing EAC PDOs with single cell digestion is suitable for most experiments requiring cell number control, uniform density, and a hollow structure that facilitates size tracking. However, the single cell-based method shows slower growth in culture as well as after re-cultivation from frozen stocks. Besides, subculturing with single cell digestion is characterized by forming hollow structures with a hollow core. In contrast, processing EAC PDOs without single cell digestion is favorable for cryopreservation, expansion, and histological characterization. In this protocol, the advantages and disadvantages of subculturing and cryopreservation of EAC PDOs with and without single cell digestion are described to enable researchers to choose an appropriate method to process and investigate their organoids.
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http://dx.doi.org/10.3791/63281DOI Listing
July 2022

Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature.

Front Endocrinol (Lausanne) 2022 29;13:904986. Epub 2022 Jun 29.

Department of General, Visceral, Cancer and Transplant Surgery, University Hospital Cologne, Cologne, Germany.

Background: Hürthle cell carcinoma (HCC) of the thyroid is rare. There are contrasting data on its clinical behavior. The aim of this study was to describe clinic-pathological features and outcomes of HCC patients at our institution, in order to adapt our surgical management.

Methods: We retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020.

Results: Patients median age was 63 years (range 29-78) with 64.7% of cases being female. Primary treatment included surgery and postoperative radioiodine therapy with 3.7 GBq in all patients. Surgery consisted of total thyroidectomy in all cases and additional central lymphadenectomy in 90.2% of cases. The median number of harvested lymph nodes was 11 (range 2-31). Lymph node involvement was found in two (4.3%) pT4a tumors. In all other cases (95.7%), central lymphadenectomy was prophylactic and lymph nodes were free of metastasis in final histopathology. Twelve (23.5%) patients with incomplete biochemical response to primary treatment were diagnosed with structural relapse during the course of disease, for which seven (58.4%) underwent resection of isolated cervical metastasis. Histopathology revealed soft tissue implants in all cases and cervical surgery led to biochemical and radiologic cure in only two (28.5%) cases. Five (41.6%) patients developed metastatic disease, followed by systemic therapy in two patients. Vascular invasion of the primary tumor was significantly associated with relapse (p<0.01).

Conclusions: Recurrence of HCC was common in this study. Given the low rate of lymph node metastases both in this study and in recent literature and the nature of relapse (soft tissue instead of nodal metastasis), the benefit of routine prophylactic central lymph node dissection for HCC remains unclear, especially in the absence of vascular invasion from the primary tumor.
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http://dx.doi.org/10.3389/fendo.2022.904986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276955PMC
July 2022

Transjugular intrahepatic portosystemic shunt, local thrombaspiration, and lysis for management of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vector-vaccine-induced thrombotic thrombocytopenia: a case report.

J Med Case Rep 2022 Jul 11;16(1):271. Epub 2022 Jul 11.

Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.

Introduction: Recombinant adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2 have been observed to be associated with vaccine-induced immune thrombotic thrombocytopenia. Though vaccine-induced immune thrombotic thrombocytopenia is a rare complication after vaccination with recombinant adenoviral vector vaccines, it can lead to severe complications. In vaccine-induced immune thrombotic thrombocytopenia, the vector vaccine induces heparin-independent production of platelet factor 4 autoantibodies, resulting in platelet activation and aggregation. Therefore, patients suffering from vaccine-induced immune thrombotic thrombocytopenia particularly present with signs of arterial or venous thrombosis, often at atypical sites, but also signs of bleeding due to disseminated intravascular coagulation and severe thrombocytopenia. We describe herein a rare case of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia. This case report presents the diagnosis and treatment of a healthy 29-year-old male Caucasian patient suffering from an extended portomesenteric thrombosis associated with atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia after the first dose of an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 [ChAdOx1 nCoV-19 (AZD1222)]. Therapeutic management of vaccine-induced immune thrombotic thrombocytopenia initially focused on systemic anticoagulation avoiding heparin and the application of steroids and intravenous immune globulins as per the recommendations of international societies of hematology and hemostaseology. Owing to the atraumatic splenic rupture and extended portomesenteric thrombosis, successful management of this case required splenectomy with additional placement of a transjugular intrahepatic portosystemic shunt to perform local thrombaspiration, plus repeated local lysis to reconstitute hepatopetal blood flow.

Conclusion: The complexity and wide spectrum of the clinical picture in patients suffering from vaccine-induced immune thrombotic thrombocytopenia demand an early interdisciplinary diagnostic and therapeutic approach. Severe cases of portomesenteric thrombosis in vaccine-induced immune thrombotic thrombocytopenia, refractory to conservative management, may require additional placement of a transjugular intrahepatic portosystemic shunt, thrombaspiration, thrombolysis, and surgical intervention for effective management.
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http://dx.doi.org/10.1186/s13256-022-03464-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274642PMC
July 2022

[Incidental Finding of Appendiceal Neuroendocrine Tumour].

Zentralbl Chir 2022 Jun 15;147(3):244-248. Epub 2022 Jun 15.

Klinik für Viszeral-, Allgemeine-, Tumor- und Transplantationschirurgie, Universitätsklinikum Köln, Koln, Deutschland.

With an incidence of 80%, neuroendocrine neoplasia (NEN) is the most common neoplasia of the appendix. In most cases, these tumours are diagnosed as an incidental finding after appendectomy with suspected appendicitis. They are usually highly differentiated neuroendocrine tumours. Due to their frequent location on the apex of the appendix, the NENs of the appendix are usually not the cause of the symptoms typical for appendicitis.Most patients (80-90%) receive adequate oncological treatment by laparoscopic or open appendectomy that has already been performed. However, if there are risk factors such as tumour size > 2 cm, location close to the base, angioinvasion, perforation or infiltration of neighbouring organs, proliferation index of > 2% or infiltration of the mesoappendix by more than 3 mm in the final histopathological finding, subsequent resection as an oncological right sided hemicolectomy is recommended .Due to their mostly early tumour stage at diagnosis without proven lymph node metastasis, patients with NEN of the appendix have an excellent 5-year survival rate of 70-85% across all tumour stages.
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http://dx.doi.org/10.1055/a-1798-0646DOI Listing
June 2022

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options.

Cancers (Basel) 2022 May 31;14(11). Epub 2022 May 31.

Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.

In rare diseases such as adrenocortical carcinoma (ACC), in silico analysis can help select promising therapy options. We screened all drugs approved by the FDA and those in current clinical studies to identify drugs that target genomic alterations, also known to be present in patients with ACC. We identified FDA-approved drugs in the My Cancer Genome and National Cancer Institute databases and identified genetic alterations that could predict drug response. In total, 155 FDA-approved drugs and 905 drugs in clinical trials were identified and linked to 375 genes of 89 TCGA patients. The most frequent potentially targetable genetic alterations included TP53 (20%), BRD9 (13%), TERT (13%), CTNNB1 (13%), CDK4 (7%), FLT4 (7%), and MDM2 (7%). We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials.
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http://dx.doi.org/10.3390/cancers14112721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179357PMC
May 2022

Resistance Mechanisms of the Metastatic Tumor Microenvironment to Anti-Angiogenic Therapy.

Front Oncol 2022 19;12:897927. Epub 2022 May 19.

Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Angiogenesis describes the formation of blood vessels from an existing vascular network. Anti-angiogenic drugs that target tumor blood vessels have become standard of care in many cancer entities. Though very promising results in preclinical evaluation, anti-angiogenic treatments fell short of expectations in clinical trials. Patients develop resistance over time or are primarily refractory to anti-angiogenic therapies similar to conventional chemotherapy. To further improve efficacy and outcome to these therapies, a deeper understanding of mechanisms that mediate resistance to anti-angiogenic therapies is needed. The field has done tremendous efforts to gain knowledge about how tumors engage tumor cell and microenvironmental mechanisms to do so. This review highlights the current state of knowledge with special focus on the metastatic tumor site and potential therapeutic relevance of this understanding from a translational and clinical perspective.
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http://dx.doi.org/10.3389/fonc.2022.897927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162757PMC
May 2022

Characteristics of the cancer stem cell niche and therapeutic strategies.

Stem Cell Res Ther 2022 06 3;13(1):233. Epub 2022 Jun 3.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.

Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in the case of their healthy counterparts, these anatomical regions are termed "niche." Thus far, a large volume of studies have shown that CSC niches take part in the maintenance, regulation of renewal, differentiation and plasticity of CSCs. In this review, we summarize and discuss the latest findings regarding CSC niche morphology, physical terrain, main signaling pathways and interactions within them. The cellular and molecular components of CSCs also involve genetic and epigenetic modulations that mediate and support their maintenance, ultimately leading to cancer progression. It suggests that the crosstalk between CSCs and their niche plays an important role regarding therapy resistance and recurrence. In addition, we updated diverse therapeutic strategies in different cancers in basic research and clinical trials in this review. Understanding the complex heterogeneity of CSC niches is a necessary pre-requisite for designing superior therapeutic strategies to target CSC-specific factors and/or components of the CSC niche.
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http://dx.doi.org/10.1186/s13287-022-02904-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166529PMC
June 2022

Influence of patient sex on outcomes after pancreatic surgery: multicentre study.

Br J Surg 2022 07;109(8):746-753

Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.

Background: Recent findings support the hypothesis of sex-related differences in inflammatory and immunological responses to trauma. The aim of this study was to address sex-specific aspects in patients who underwent pancreatic surgery.

Methods: This retrospective study used data from the German StuDoQ registry. Patients who underwent pancreatic surgery between 2010 and 2020 were stratified according to procedure (pancreatic head resection, distal pancreatectomy (DP), total pancreatectomy (TP)). Each cohort underwent propensity score matching (PSM) with the co-variables BMI, ASA, age, coronary heart disease (CHD), diabetes, hypertension with medication, and histology to level the distribution of co-morbidities between men and women. The main outcomes were morbidity and mortality.

Results: The total cohort consisted of 10 224 patients (45.3 per cent women). Men had higher ASA grades, and more often had CHD, diabetes, and hypertension with medication. Women had fewer overall complications (57.3 versus 60.1 per cent; P = 0.005) and a lower mortality rate (3.4 versus 4.9 per cent; P < 0.001). Rates of pancreatic surgery-specific complications, such as clinically relevant postoperative pancreatic fistula (POPF) (grade B/C: 14 versus 17 per cent; P < 0.001), delayed gastric emptying (grade B/C: 7.8 versus 9.2 per cent; P = 0.014), and postpancreatectomy haemorrhage (grade B/C: 7.1 versus 9.0 per cent; P < 0.001), were also lower in women. After PSM, 8358 patients were analysed. In the pancreatic head resection cohort (5318 patients), women had fewer complications (58.6 versus 61.4 per cent; P = 0.044), a lower in-hospital mortality rate (3.6 versus 6.1 per cent; P < 0.001), and less often had clinically relevant POPF (11.6 versus 16.2 per cent; P < 0.001). After DP, the clinically relevant POPF rate was lower in women (22.5 versus 27.3 per cent; P = 0.012). In the TP cohort, men more often developed intra-abdominal abscess requiring drainage (5.0 versus 2.3 per cent; P = 0.050).

Conclusion: Women had favourable outcomes after pancreatic surgery.
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http://dx.doi.org/10.1093/bjs/znac128DOI Listing
July 2022

Adrenal Surgery in the Era of Multidisciplinary Endocrine Tumor Boards.

Horm Metab Res 2022 May 9;54(5):294-299. Epub 2022 May 9.

Department of General, Visceral, Cancer and Transplant Surgery, University Hospital Cologne, Cologne, Germany.

Work up of adrenal masses includes assessment of endocrine activity and malignancy risk. There is no indication for surgical removal of nonfunctional adrenal adenomas, according to the guidelines. In the present study, we aimed at evaluating the impact of a university endocrine tumor board on the quality of the indications for adrenal surgery at our institution. One hundred consecutive patients receiving primary adrenal surgery at the University Hospital of Cologne, Germany were included. Their demographics, clinic-pathologic characteristics, treatment and outcome were analyzed. In 55 (55%) cases, indication for surgery consisted in functional benign tumors, including Conn, Cushing adenomas and pheochromocytomas. Forty (40%) tumors were referred to surgery for malignancy suspicion and 5 (5%) myelolipomas were removed due to their size. Eighty-nine percent of surgeries were performed as minimally invasive procedures. Overall morbidity included two (2%) self-limiting pancreatic fistulas after left laparoscopic adrenalectomy for pheochromocytoma. All functional tumors were confirmed benign by final histology. Only 33 (82.5%) of 40 suspicious cases turned out to be malignant. Consequently, nonfunctional benign adenomas were "unnecessarily" removed in only 7 (7%) patients, with 6 (85.7%) of them having a history of extra-adrenal cancer and all of them fulfilling criteria for surgery, according to the international guidelines. In conclusion, the endocrine tumor board provided an excellent adherence to the guidelines with most surgeries being performed either for functional or malignant tumors. In nonfunctional tumors with history of extra adrenal cancer, CT guided biopsy might be considered for obviating surgery.
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http://dx.doi.org/10.1055/a-1808-7239DOI Listing
May 2022

Robot-assisted minimally invasive esophagectomy (RAMIE) vs. hybrid minimally invasive esophagectomy: propensity score matched short-term outcome analysis of a European high-volume center.

Surg Endosc 2022 May 3. Epub 2022 May 3.

Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.

Introduction: Transthoracic esophagectomy is a highly complex and sophisticated procedure with high morbidity rates and a significant mortality. Surgical access has consistently become less invasive, transitioning from open esophagectomy to hybrid esophagectomy (HE) then to totally minimally invasive esophagectomy (MIE), and most recently to robot-assisted minimally invasive esophagectomy (RAMIE), with each step demonstrating improved patient outcomes. Aim of this study with more than 600 patients is to complete a propensity-score matched comparison of postoperative short-term outcomes after highly standardized RAMIE vs. HE in a European high volume center.

Patients And Methods: Six hundred and eleven patients that underwent transthoracic Ivor-Lewis esophagectomy for esophageal cancer between May 2016 and May 2021 were included in the study. In January 2019, we implemented an updated robotic standardized anastomotic technique using a circular stapler and ICG (indocyanine green) for RAMIE cases. Data were retrospectively analyzed from a prospectively maintained IRB-approved database. Outcomes of patients undergoing standardized RAMIE from January 2019 to May 2021 were compared to our overall cohort from May 2016-April 2021 (HE) after a propensity-score matching analysis was performed.

Results: Six hundred and eleven patients were analyzed. 107 patients underwent RAMIE. Of these, a total of 76 patients underwent a robotic thoracic reconstruction using the updated standardized circular stapled anastomosis (RAMIE group). A total of 535 patients underwent HE (Hybrid group). Seventy patients were propensity-score matched in each group and analysis revealed no statistically significant differences in baseline characteristics. RAMIE patients had a significantly shorter ICU stay (p = 0.0218). Significantly more patients had no postoperative complications (Clavien Dindo 0) in the RAMIE group [47.1% vs. 27.1% in the HE group (p = 0.0225)]. No difference was seen in lymph node yield and R0 resection rates. Anastomotic leakage rates when matched were 14.3% in the hybrid group vs. 4.3% in the RAMIE group (p = 0.07).

Conclusion: Our analysis confirms the safety and feasibility of RAMIE and HE in a large cohort after propensity score matching. A regular postoperative course (Clavien-Dindo 0) and a shorter ICU stay were seen significantly more often after RAMIE compared to HE. Furthermore it shows that both procedures provide excellent short-term oncologic outcomes, regarding lymph node harvest and R0 resection rates. A randomized controlled trial comparing RAMIE and HE is still pending and will hopefully contribute to ongoing discussions.
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http://dx.doi.org/10.1007/s00464-022-09254-2DOI Listing
May 2022

Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma.

J Cancer Res Clin Oncol 2022 Sep 27;148(9):2287-2293. Epub 2022 Apr 27.

Institute of Pathology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Introduction: Despite modern multimodal therapeutic regimens, the prognosis of esophageal adenocarcinoma (EAC) is still poor and there is a lack of biological markers estimating the patients' prognosis. Fructose-1,6-biphosphatase (FBP1) is a key enzyme in gluconeogenesis and is associated with tumor initiation in several cancers. Therefore, this study aims to characterize its implication for EAC patients.

Methods And Materials: A total of 571 EAC patients who underwent multimodal treatment between 1999 and 2017 were analyzed for FBP1 expression using immunohistochemistry.

Results: 82.5% of the EACs show FBP1 expression in the tumor albeit with different intensities categorizing specimens accordingly into score 0 (no expression), score 1 (weak expression), score 2 (moderate expression) and score 3 (strong expression) (score 1 = 25.0%, score 2 = 35.9%, score 3 = 21.5%). Intratumoral FBP1 expression was significantly associated with a better prognosis (p = 0.024). This observation was particularly relevant among patients who received primary surgery without neoadjuvant treatment (p = 0.004). In multivariate analysis, elevated FBP1 expression was an independent biomarker associated with a favorable prognosis.

Discussion: Despite being associated with a favorable prognosis, the majority of patients with high FBP1 expression also require individualized therapy options to ensure long-term survival. Recently, it has been shown that the presence of the FBP1 protein increases the sensitivity of pancreatic cancer cells to the bromodomain and extraterminal domain (BET) inhibitor JQ1.

Conclusion: We described for the first time the prognostic and possibly therapeutic relevance of FBP1 in EAC. The efficiency of the BET inhibitor in EAC should be verified in clinical studies and special attention should be paid to the effects of neoadjuvant therapy on FBP1 expression.
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http://dx.doi.org/10.1007/s00432-022-04025-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349078PMC
September 2022

[Synopsis-S3 guidelines pancreatic cancer].

Chirurg 2022 05 26;93(5):427-428. Epub 2022 Apr 26.

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland.

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http://dx.doi.org/10.1007/s00104-022-01637-4DOI Listing
May 2022

Effect of phone call distraction on the performance of medical students in an OSCE.

BMC Med Educ 2022 Apr 20;22(1):295. Epub 2022 Apr 20.

Department of General, Visceral, Cancer And Transplant Surgery, University of Cologne, Cologne, Germany.

Background: The usage of smartphones in the daily clinical routine is an essential aspect however it seems that they also present an important distractor that needs to be evaluated. The aim of this prospective study was the evaluation of the influence of phone calls as distractors on the performance levels of medical students during an objective structured clinical examination (OSCE), simulating the normal clinical practice.

Methods: As the goal of an OSCE presents the examination of clinical skills of medical students in a realistic setting, more than 100 students recruited from the university hospital of Cologne participated in either OSCE I or II. During the OSCE I intravenous cannulation was simulated while OSCE II simulated an acute abdominal pain station. Participants had to perform each of these stations under two circumstances: a normal simulated OSCE and an OSCE station with phone call distraction. Their performance during both simulations was then evaluated.

Results: In OSCE I students achieved significantly more points in the intravenous cannulation station if they were not distracted by phone calls (M=6.44 vs M=5.95). In OSCE II students achieved significantly more points in the acute abdominal pain station if they were not distracted by phone calls (M=7.59 vs M=6.84). While comparing only those students that completed both stations in OSCE I/II participating students achieved significantly more points in both OSCE I and II if they were not distracted by phone calls.

Conclusion: The presented data shows that phone call distraction decreases the performance level of medical students during an OSCE station. Therefore, it is an indicator that distraction especially for younger doctors should be held to a minimum. On a second note distraction should be integrated in the medical education system as it plays an important role in clinical routine.
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http://dx.doi.org/10.1186/s12909-022-03215-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020121PMC
April 2022

[ASCO guidelines for the management of stage III NSCLC part 5: inoperable patients].

Chirurgie (Heidelb) 2022 Jun 12;93(6):608-609. Epub 2022 Apr 12.

Klinik und Poliklinik Allgemein‑, Viszeral- und Tumorchirurgie, Universität zu Köln, Kerpener Str. 62, 50931, Köln, Deutschland.

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http://dx.doi.org/10.1007/s00104-022-01643-6DOI Listing
June 2022

Long-Term Outcome After Histopathological Complete Response with and Without Nodal Metastases Following Multimodal Treatment of Esophageal Cancer.

Ann Surg Oncol 2022 Apr 11. Epub 2022 Apr 11.

Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Background: This study analyzed the long-term survival after pathological complete response (pCR) with and without nodal metastases and associated recurrence following multimodal treatment of esophageal cancer. The recurrence pattern after pCR is of importance for different postoperative surveillance strategies.

Methods: A cohort of 890 patients with esophageal cancer received neoadjuvant therapy followed by transthoracic esophagectomy. Only patients with pCR of the primary tumor with and without nodal metastasis were analyzed. A clinicopathological database was set up and completed with long-term follow up information on recurrent disease.

Results: The specimen of 201 patients (23%) demonstrated pCR, 84% without (ypT0N0) and 16% with residual nodal disease (ypT0N+). For ypT0N0 patients, the 5-year overall survival was significantly higher than for patients with metastatic nodes (77% vs. 24%) (p < 0.0001). Sixty-eight percent of patients had no evidence of tumor recurrence, whereas 32% had proven relapse. For patients with and without tumor recurrence, 5-year survival rates were 14% and 93%, respectively (p < 0.0001). For patients with recurrent disease, median survival time was 27 for locoregional, 44 for distant, and 24 months for combined recurrence (p = 0.302). In the multivariable Cox-regression analysis, node-positive disease predicted both locoregional and metastatic recurrence.

Conclusions: Pathological CR offers long-term survival in patients without nodal metastases but outcome significantly deteriorates with the presence of nodal metastases. Follow-up recommendations may therefore be adopted in patients with pCR. Furthermore, "watch-and-wait" surveillance strategies with suspected clinical complete response have to be considered with caution.
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http://dx.doi.org/10.1245/s10434-022-11700-3DOI Listing
April 2022

[ASCO guidelines for the treatment of stage III NSCLC part 4: indications for adjuvant therapy].

Chirurg 2022 05 4;93(5):518-519. Epub 2022 Apr 4.

Klinik und Poliklinik Allgemein‑, Viszeral- und Tumorchirurgie, Universität zu Köln, Kerpener Str. 62, 50931, Köln, Deutschland.

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http://dx.doi.org/10.1007/s00104-022-01635-6DOI Listing
May 2022

[Surgical treatment of pancreatic cancer-What is new?]

Chirurg 2022 May 31;93(5):446-452. Epub 2022 Mar 31.

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland.

The incidence of pancreatic ductal adenocarcinoma is continuously increasing and will become the second leading cause of cancer-related death in Europe and the USA by 2030. With a 5-year overall survival rate of less than 10% the prognosis remains poor. So far surgical tumor resection remains the only curative treatment option, which is now partially supported by multimodal neoadjuvant and adjuvant therapy concepts. Due to the aggressive tumor biology patients with advanced pancreatic cancer in particular can profit from these multimodal therapy concepts. Additionally, in recent years surgical treatment was optimized, the criteria for tumor resectablity were defined and minimally invasive surgery was widely introduced. This review article summarizes the newest developments and the new German S3 guidelines concerning surgery of pancreatic cancer.
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http://dx.doi.org/10.1007/s00104-022-01618-7DOI Listing
May 2022

Outcome of prophylactic endoscopic vacuum therapy for high-risk anastomosis after esophagectomy.

Minim Invasive Ther Allied Technol 2022 Mar 28:1-7. Epub 2022 Mar 28.

Department of General, Visceral, Cancer and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.

Endoscopic vacuum therapy (EVT) has become an established procedure for the treatment of anastomotic leaks (AL) in upper gastrointestinal surgery. A novel approach is the use of EVT for preventing leaks in high-risk anastomosis. The aim of this study was to analyze the outcome of prophylactic EVT (pEVT) in patients receiving surgical revision of the anastomosis after oncological Ivor-Lewis esophagectomy (ILE) due to AL. Between June 2016 and February 2019, all patients who underwent anastomotic revision after ILE due to a confirmed AL were included. The primary outcome was the success rate of pEVT, which was defined as absence of an AL after revision. Secondary outcome parameters were duration of treatment, inflammatory levels, and ICU/hospital stay. Twenty-one patients underwent anastomotic revision due to an AL. The cause of the AL was ischemia in nine patients (42.9%) and non-ischemia (other) in 12 patients (57.1%). PEVT was performed in 14 patients (66.6%). The overall success rate of pEVT was five out of 14 patients (35.7%). Prophylactic EVT cannot prevent a re-leak in patients with high-risk anastomosis due to surgical revision of an AL after oncological ILE. However, pEVT might help to control the clinical condition of these patients.
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http://dx.doi.org/10.1080/13645706.2022.2051719DOI Listing
March 2022

International Tumor Budding Consensus Conference criteria determine the prognosis of oesophageal adenocarcinoma with poor response to neoadjuvant treatment.

Pathol Res Pract 2022 Apr 15;232:153844. Epub 2022 Mar 15.

University of Cologne Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Kerpener Strasse 62, D-50924 Cologne, Germany.

Background: Neoadjuvant therapy regimens followed by surgery represent the current standard treatment of locally advanced oesophageal adenocarcinomas. Tumour regression determines prognosis, but more than half of patients do have more than 10% residual tumour after neoadjuvant therapy. In these cases, classical histopathological parameters for the determination of prognosis are of limited value. Therefore, we investigated whether tumour budding could be an additional prognostic factor for tumours with poor response to neoadjuvant therapy.

Methods: Tumour budding was assessed according to a standardized consensus quantification method as proposed by the International Tumor Budding Consensus Conference (ITBCC) in H&E-stained whole tissue slides of 278 formalin-fixed paraffin-embedded (FFPE) resected oesophageal adenocarcinomas with a poor response (> 10% vital residual tumour) to neoadjuvant therapy.

Results: We could demonstrate a strong positive correlation (p < 0.05) between the budding group, ypN stage and UICC tumour stage. Further, high numbers of tumour buds were a significant and independent negative prognostic marker for OS in all studied patients (HR = 1.039 (95% CI 1.012-1.066), p = 0.004). ITBCC budding groups were an independent prognostic parameter.

Conclusions: Tumour budding assessed in accordance with the ITBCC criteria may aid in the prognostic stratification of locally advanced oesophageal adenocarcinoma with poor response to neoadjuvant treatment.
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http://dx.doi.org/10.1016/j.prp.2022.153844DOI Listing
April 2022

Anaplastic thyroid cancer: genome-based search for new targeted therapy options.

Endocr Connect 2022 Apr 29;11(4). Epub 2022 Apr 29.

Department of General, Visceral, Tumor and Transplant Surgery, University Hospital Cologne, Cologne, Germany.

Objective: Anaplastic thyroid cancer (ATC) is one of the most lethal human cancers with meager treatment options. We aimed to identify the targeted drugs already approved by the Food and Drug Administration (FDA) for solid cancer in general, which could be effective in ATC.

Design: Database mining.

Methods: FDA-approved drugs for targeted therapy were identified by screening the databases of MyCancerGenome and the National Cancer Institute. Drugs were linked to the target genes by querying Drugbank. Subsequently, MyCancerGenome, CIViC, TARGET and OncoKB were mined for genetic alterations which are predicted to lead to drug sensitivity or resistance. We searched the Cancer Genome Atlas database (TCGA) for patients with ATC and probed their sequencing data for genetic alterations which predict a drug response.

Results: In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified. Seventeen (52%) of 33 patients found in TCGA had at least one genetic alteration in targetable genes. The point mutation BRAF V600E was seen in 45% of patients. PIK3CA occurred in 18% of cases. Amplifications of ALK and SRC were detected in 3% of cases, respectively. Fifteen percent of the patients displayed a co-mutation of BRAF and PIK3CA. Besides BRAF-inhibitors, the PIK3CA-inhibitor copanlisib showed a genetically predicted response. The 146 (94%) remaining drugs showed no or low (under 4% cases) genetically predicted drug response.

Conclusions: While ATC carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.
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http://dx.doi.org/10.1530/EC-21-0624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066601PMC
April 2022

Lymphatic Vessel Invasion in Routine Pathology Reports of Papillary Thyroid Cancer.

Front Med (Lausanne) 2022 21;9:841550. Epub 2022 Feb 21.

Institute for Pathology, University Clinic of Cologne, Cologne, Germany.

Purpose: It is not mandatory to report lymphatic vessel invasion in pathology reports of papillary thyroid cancer (PTC) according to the current Union for International Cancer Control (UICC) TNM (tumor, nodes, and metastases) classification. However, there is some evidence for its correlation with lymph node metastasis (LNM) and prognosis. The aim of this study was to explore the clinical implication of lymphatic vessel invasion documentation of PTC because pathology reports play a pivotal role in postsurgical clinical decision-making in endocrine tumor boards.

Methods: Patients undergoing postoperative radioiodine treatment for PTC at the University Hospital of Cologne, Germany between December 2015 and March 2020 were identified. Pathology reports were screened for documentation of lymphatic vessel invasion. Demographics and clinicopathologic data of patients documented, including lymphatic vessel invasion and lymph nodal involvement were analyzed.

Results: A total of 578 patients were identified and included. Lymphatic vessel invasion was reported in pathology reports of 366 (63.3%) and omitted in 112 (36.7%) patients. Positive lymphatic vessel invasion (L1) was diagnosed in 67 (18.3%) of 366 patients and was documented as absent (L0) in 299 (81.7%) patients. Lymph nodal (N) status was positive (N+) in 126 (45.6%) and negative (N0) in 150 (54.3%) of these patients. In 54 (80.6%) L1 cases N+ status and in 137 (65.6%) L0 cases N0 status was diagnosed. In 13 (19.4%) cases with L1 status, there were no LNMs (L1 N0). In total, 72 (34.4%) patients had LNM despite L0 status (L0 N+). The sensitivity and specificity of LVI reporting for LNM were 0.42 and 0.91, respectively.

Conclusion: In routine pathology reports of PTC used for indication to postoperative radioiodine treatment by a German endocrine tumor board, lymphatic vessel invasion was found to be reported inconsistently and mostly as L0. L1 diagnoses, however, reliably correlated with reported LNM and might, thus, be relevant for clinical decision-making. For this reason, we advocate for standardized pathologic reassessment of lymphatic vessel invasion, in particular for cases where lymph nodes are not included in the pathologic specimen and if L0 is documented.
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http://dx.doi.org/10.3389/fmed.2022.841550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899077PMC
February 2022

Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival.

Sci Rep 2022 03 4;12(1):3584. Epub 2022 Mar 4.

Department of Gastroenterology and Hepatology, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2-19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.
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http://dx.doi.org/10.1038/s41598-022-07580-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897453PMC
March 2022

Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance.

Clin Cancer Res 2022 04;28(8):1712-1723

Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Purpose: An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (TME) of cancer.

Experimental Design: Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared with historic data from non-immunosuppressed patients. Digital image analysis of whole-section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays.

Results: We found a remarkably reduced immune infiltrate in the center tumor (CT) regions as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8+ T cells than for CD3+ T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of TLS was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients.

Conclusions: Our study demonstrates the impact of immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-3746DOI Listing
April 2022

[ASCO guideline for the management of stage III NSCLC part 3: indications for neoadjuvant therapy].

Chirurg 2022 04 18;93(4):403-404. Epub 2022 Feb 18.

Klinik und Poliklinik Allgemein‑, Viszeral- und Tumorchirurgie, Universität zu Köln, Kerpener Str. 62, 50931, Köln, Deutschland.

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http://dx.doi.org/10.1007/s00104-022-01602-1DOI Listing
April 2022
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