Purpose This study describes the treatment of retroperitoneal sarcoma (RPS) in Germany between 2000 and 2022, comparing it to existing recommendations and guidelines. Methods Data from the cancer registries of 13 out of 15 federal states was used. Included cases had a retroperitoneal localization (ICD) and histology (ICD-O) corresponding to soft tissue sarcoma. Descriptive analyses of treatment were conducted, focusing on surgical treatment including the development of local residual status and the number of organs resected. Results Surgery was the most common treatment for cases without metastases, being performed in 79% of cases with available grading data, while systemic therapy (7.6%) and radiotherapy (6.5%) were used less frequently; treatment information was missing for 17% of cases. The most frequent surgeries involved kidneys, intestines and the adrenal gland. In over a third of the cases (38%), multiple organs were resected, especially in cases of adipocytic tumors, where the rate was 46%. Conclusion German cancer registry data allow to characterize treatment of rare diseases such as RPS by supplying detailed information on tumor site and histology. Data quality of German cancer registries improved over time. Treatment patterns of RPS in Germany appear to follow current recommendations regarding extent of surgery and multimodal treatment. The findings align with existing cohort studies from expert centers and (inter-) national guidelines, emphasizing surgery as the only curative option, with multivisceral resection being the preferred approach, especially for adipocytic tumors. Despite potential limitations due to underreporting, cancer registry data provides valuable insights into the medical care situation of the rare RPS.

Empirical evidence shows that treatment of adult soft tissue sarcoma (STS) according to clinical guidelines has a survival benefit for patients. In 2021, the first evidence-based guidelines for STS were published in Germany including 14 measurable quality indicators (QIs). This paper examines the quality of care of STS in Germany across all treatment institutions prior to the publication of the clinical guideline using the QIs.A comprehensive population-based cohort of 20,922 sarcoma patients from 11 of 16 federal states, diagnosed between 2015 and 2021 was extracted from the cancer registry data using the ICD-O-3-codes for topography and histological subtype. The QI measurements are based on the calculation rules of a group of experts. Annual percentage changes (APCs) were calculated to identify trends over time.QI 1 (Pre-therapeutic presentation in the tumor board (initial diagnosis of STS)) increased from 9 % to 24 %. QI 7 (R0 resection for STS) showed a stable rate of over 80 %. For QI 8 (hysterectomy without morcellation for sarcoma confined to the uterus), the rate was 82 % in 2015 and rose significantly until 2017 to 94 %. QI 12 (First-line chemotherapy for STS without GIST) remained at the same level as the overall value of 79 %. For QI 14 (Postoperative mortality in retroperitoneal sarcoma), the value for the entire period was 1.4 %.The extensive database enables QI analysis for sarcoma care. Improvements in defined QIs confirm progress, while unmet targets are identifiable. Using cancer-registry data ensures comprehensive coverage of all institutions treating sarcoma patients, extending beyond accredited sarcoma centers. Results may serve as baseline values for future evaluations of improvements in patient care following implementation of the S3 guideline.

Protein synthesis is an essential process, deregulated in multiple tumor types showing differential dependence on translation factors compared to untransformed tissue. We show that colorectal cancer (CRC) with loss-of-function mutation in the APC tumor suppressor depends on an oncogenic translation program regulated by the ability to sense phosphorylated eIF2α (p-eIF2α). Despite increased protein synthesis rates following APC loss, eIF2α phosphorylation, typically associated with translation inhibition, is enhanced in CRC. Elevated p-eIF2α, and its proper sensing by the decameric eIF2B complex, are essential to balance translation. Knockdown or mutation of eIF2Bα and eIF2Bδ, two eIF2B subunits responsible for sensing p-eIF2α, impairs CRC viability, demonstrating that the eIF2B/p-eIF2α nexus is vital for CRC. Specifically, the decameric eIF2B linked by two eIF2Bα subunits is critical for translating growth-promoting mRNAs which are induced upon APC loss. Depletion of eIF2Bα in APC-deficient murine and patient-derived organoids establishes a therapeutic window, validating eIF2Bα as a target for clinical intervention. In conclusion, we demonstrate how the expression of the oncogenic signature in CRC is crucially controlled at the translational level.

PURPOSE:The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers. METHODS:In this cross-sectional case-based survey study, 5 anonymized patient cases with imaging data of localized STS were presented to MTBs of 21 German-speaking tertiary referral hospitals. Centers provided recommendations on treatment sequence and modalities, along with the consensus level within their MTB. Agreement percentages were calculated, and consensus levels were rated on a scale of 1 to 10. RESULTS:Five patient cases were discussed resulting in 105 recommendations. Agreement percentages for case 1 to 5 were 14.3%, 61.9%, 33.3%, 52.4% and 9.3%, with a median agreement percentage of 33.3%. Grouping pre- and postoperative therapies as "perioperative" and including recommendations with and without regional hyperthermia raised the median agreement to 47.6%. The mean consensus level within each center across all 5 cases was 9.5. CONCLUSION:This first case-based analysis of inter-center agreement for STS management in German-speaking countries reveals low inter-center agreement but high intra-center consensus. Our study includes nearly all tertiary sarcoma centers in German-speaking countries, affirming its strong external validity. These findings suggest potential and clinically very relevant differences in treatment standards among sarcoma centers. Enhanced case-based exchanges and collaborative efforts are needed to reduce discrepancies and standardize the management of STS patients.

BackgroundDedifferentiated liposarcoma (DDLPS) is a rare mesenchymal cancer originating from the adipose tissue, with poor survival rates for most patients, highlighting the critical need for novel treatment options.Case descriptionThis report examines the efficacy and safety of sequential pre-treatment with the marine-derived alkaloid trabectedin followed by checkpoint inhibition using the anti-PD-1 antibody nivolumab in a 63-year-old male patient with unresectable retroperitoneal DDLPS. Treatment was initiated at the time of the seventh relapse as part of the NitraSarc phase 2 multicenter trial for inoperable soft tissue sarcoma conducted by the German Interdisciplinary Sarcoma Group (GISG-15, NCT03590210). The patient demonstrated an immediate tumor response, and in combination with minor surgery, achieved R0 resection status, which was subsequently maintained without the need for further therapy for the past 52 months. Correlative molecular analyses revealed a sustained DNA damage repair machinery and downregulation of PD-1 protein expression in post-treatment tumor samples.ConclusionThis report provides exemplary insight on the feasibility and efficacy of sequential pre-treatment with trabectedin as a priming strategy for PD-1 inhibition in advanced DDLPS. Full trial results from NitraSarc are pending for publication.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness and safety of total neoadjuvant therapy versus standard therapy in individuals with locally advanced rectal cancer.

BACKGROUND:Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors. METHODS:In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed. A mixed effects model was applied to evaluate multiple survival events per patient. RESULTS:Median overall survival (OS) after first metastasis was 5.4 years with 1-, 2- and 5-year survival rates of 93.7, 81.7, and 53.1 %, respectively. A treatment-free interval ≥12 months and treatment of liver metastases were positively correlated with progression-free survival (PFS) after LAT (HR = 0.61, p = 0.00032 and HR = 0.52, p = 0.0081, respectively). A treatment-free interval ≥12 months and treatment of metastatic lesions in a single organ site other than lung and liver were positive prognostic factors for OS after first LAT (HR = 0.50, p = 0.028 and HR = 0.40, p = 0.026, respectively) while rare histotypes and LAT other than surgery and radiotherapy were negatively associated with OS after first LAT (HR = 2.56, p = 0.020 and HR = 3.87, p = 0.025). Additional systemic therapy was independently associated with a PFS benefit in patients ≤60 years with ≥4 metastatic lesions (for max. diameter of treated lesions ≤2 cm: HR = 0.32, p = 0.02 and >2 cm: HR = 0.20, p = 0.0011, respectively). CONCLUSION:This multicenter study conducted at six German university hospitals underlines the value of LAT in metastatic STS. The exceptionally high survival rates are likely to be associated with patient selection and treatment in specialized sarcoma centers.

Die Qualifizierung von Beschwerden und Leidensdruck und der damit einhergehenden Einschränkung der Lebensqualität gestaltet sich bei Patienten, die an Stuhlinkontinenz erkrankt sind, häufig schwierig. Einteilungen der Stuhlinkontinenz in Subtypen oder Grade bilden das reale Beschwerdebild der Patienten nur bedingt ab. Verschiedene Scoringsysteme wurden daher entwickelt, um einen objektivierbaren Vergleich der subjektiv empfundenen Symptome der Patienten zu ermöglichen. Hierdurch sollen konservative oder chirurgische Therapieerfolge anhand der Beschwerden und der Beeinträchtigung der Lebensqualität der betroffenen Patienten durch einfache objektivierbare und reproduzierbare Fragen ermittelt und in einem Score zusammengefasst werden. Im folgenden Manuskript werden die gängigsten Scoringsysteme erläutert und die jeweiligen Vor- und Nachteile der einzelnen Scores dargestellt.

Desmoplastic small round cell tumor (DSRCT) is a rare, radiosensitive, yet difficult-to-treat sarcoma subtype affecting predominantly male adolescents. Extensive intraperitoneal seeding is common and requires multimodal management. With no standard therapy established, the prognosis remains poor, and new treatment options are needed. We demonstrate the clinical potential of C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging and endoradiotherapy in DSRCT. Methods: Eight male patients underwent dual-tracer imaging with [18F]FDG and CXCR4-directed [68Ga]pentixafor PET/CT. A visual comparison of both tracers, along with uptake quantification in active DSRCT lesions, was performed. [68Ga]pentixafor uptake was correlated with immunohistochemical CXCR4 expression on tumor cells. Four patients with end-stage progressive disease underwent CXCR4-based endoradiotherapy. We report the safety, response by RECIST 1.1, and survival after endoradiotherapy. Results: Uptake of [68Ga]pentixafor in tumor lesions was demonstrated in all patients with DSRCT, providing diagnostic power comparable to [18F]FDG PET. Corresponding CXCR4 expression was confirmed by immunohistochemistry in all DSRCT biopsies. Finally, 4 patients were treated with CXCR4-directed [90Y]endoradiotherapy, 3 in a myeloablative dose range with subsequent autologous stem cell transplantation. All 3 required transfusions, and febrile neutropenia occurred in 2 patients (resulting in 1 death). Notably, severe nonhematologic adverse events were absent. We observed signs of response in all 3 patients, translating into disease stabilization in 2 patients for 143 and 176 d, respectively. In the third patient, postmortem autopsy confirmed a partial pathologic response. Conclusion: We validated CXCR4 as a diagnostic biomarker and a promising target for endoradiotherapy in DSRCT, demonstrated its feasibility, and provided the first evidence of its clinical efficacy.

OBJECTIVE:Adrenal resections are rare procedures of a heterogeneous nature. While recent European guidelines advocate a minimum annual caseload for adrenalectomies (6 per surgeon), evidence for a volume-outcome relationship for this surgery remains limited.DESIGN:A retrospective analysis of all adrenal resections in Germany between 2009 and 2017 using hospital billing data was performed. Hospitals were grouped into three tertiles of approximately equal patient volume.METHODS:Descriptive, univariate, and multivariate analyses were applied to identify a possible volume-outcome relationship (complications, complication management, and mortality).RESULTS:Around 17 040 primary adrenal resections were included. Benign adrenal tumors (n = 8,213, 48.2%) and adrenal metastases of extra-adrenal malignancies (n = 3582, 21.0%) were the most common diagnoses. Six hundred and thirty-two low-volume hospitals performed an equal number of resections as 23 high-volume hospitals (median surgeries/hospital/year 3 versus 31, P < .001). Complications were less frequent in high-volume hospitals (23.1% in low-volume hospitals versus 17.3% in high-volume hospitals, P < .001). The most common complication was bleeding in 2027 cases (11.9%) with a mortality of 4.6% (94 patients). Overall in-house mortality was 0.7% (n = 126). Age, malignancy, an accompanying resection, complications, and open surgery were associated with in-house mortality. In univariate analysis, surgery in high-volume hospitals was associated with lower mortality (OR: 0.47, P < .001). In a multivariate model, the tendency remained equal (OR: 0.59, P = .104). Regarding failure to rescue (death in case of complications), there was a trend toward lower mortality in high-volume hospitals.CONCLUSIONS:The annual caseload of adrenal resections varies considerably among German hospitals. Our findings suggest that surgery in high-volume centers is advantageous for patient outcomes although fatal complications are rare.

Die junge Generation von Chirurgen/innen stellt neue Anforderungen an Weiterbildung und Arbeitsbedingungen. Häufig wird dies mit einer mangelnden Leistungsbereitschaft gleichgesetzt. Vielmehr besteht jedoch der Anspruch an eine hochwertige Ausbildung mit dem Ziel des Kompetenzerwerbs im operativen und perioperativen Setting sowie auf verantwortungsvolle Arbeitszeitmodelle. Ziel dieses Artikels ist es, die Erwartungen des chirurgischen Nachwuchses an die Weiterbildung unter aktuellen Einflussfaktoren wie einer hohen Arbeitsbelastung, der neuen Weiterbildungsordnung und den zu erwartenden Veränderungen der Krankenhauslandschaft darzustellen und Ansatzpunkte zur Optimierung der Weiterbildungs- und Arbeitsbedingungen aufzuzeigen. Grundlage dieses Artikels sind neben einer ausführlichen Literaturrecherche publizierte Meinungsbilder und Umfrageergebnisse, sowie Vorträge und Diskussionsrunden im Rahmen von Kongressen des letzten Jahres. Zur Sicherstellung einer hochwertigen, modernen Weiterbildung und um die Begeisterung für die Chirurgie aufrecht zu erhalten, müssen Optimierungsoptionen und Innovationsbedarf erkannt und lange geforderte Anpassungen an etablierte Strukturen umgesetzt werden. Ansatzpunkte dazu bieten die Etablierung flexibler Arbeitsmodelle, die strukturierte und transparente Durchführung der operativen Ausbildung unter Zuhilfenahme moderner Trainingseinheiten, vorausschauende Planung von Weiterbildungscurricula sowie neue personelle Strukturen mit einem Ausbau von Teaching- und Feedback-Kultur.

Background The young generation of surgeons sets new requirements for educational and working conditions. This is frequently interpreted as a lack of motivation to perform; however, instead there is a claim for high-quality training with the aim of acquiring competence in the operative and perioperative setting as well as for responsible working time models.Objective Aim of this article is to present expectations of surgical residents regarding residency training under current influencing factors, such as a high workload, the new training regulations or expected changes in the hospital landscape and to identify options for optimizing training and working conditions.Material and methods In addition to an extensive literature search, this article is based on published opinions and survey results as well as lectures and discussions at congresses held in the past year.Results and discussion To ensure a modern high-quality education and to maintain enthusiasm for surgery, the need for adjustments and innovation must be recognized and long-requested modifictions to established structures must be implemented. Flexible working models, the structured and transparent implementation of surgical residency training and modern training units, long-term planning of training curricula and new personnel structures with an expansion of teaching and feedback culture are options for improvement.

(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III).

Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1

BACKGROUND:Postsurgical hypoparathyroidism (PH) is the most frequent complication after thyroid surgery. The aim of this systematic review and meta-analysis is to summarize a unifying definition of PH and to elucidate the best possible approach for early detection of PH. METHODS:A systematic review of the literature according to the PICO framework using Embase, PUBMED and the Cochrane library was carried out on 1 December 2021 followed by analysis for risk of bias, data extraction and meta-analysis. All studies addressing the definition of postoperative hypoparathyroidism and/or diagnostic approaches for early detection and diagnosis were included. Case reports, commentaries, non-English articles, book chapters and pilot studies and reviews were excluded. RESULTS:From 13 704 articles, 188 articles were eligible for inclusion and further analysis. These articles provided heterogeneous definitions of PH. Meta-analysis revealed that postoperative measurements of parathormone (PTH) levels have a higher sensitivity and specificity than intraoperative PTH measurements to predict PH after thyroid surgery. None of the timeframes analysed after surgery within the first postoperative day (POD1) was superior to predict the onset of PH. PTH levels of less than 15 pg/ml and less than 10 pg/ml are both reliable threshold levels to predict the postoperative onset of PH. A relative reduction of mean(s.d.) PTH levels from pre- to postoperative values of 73 (standard deviation 11) per cent may also be predictive for the development of PH. The estimation of calcium levels on POD1 are recommended. CONCLUSION:PH is best defined as an undetectable or inappropriately low postoperative PTH level in the context of hypocalcaemia with or without hypocalcaemic symptoms. PTH levels should be measured after surgery within 24 h. Both threshold levels below 10 and 15 pg/ml or relative loss of PTH before/after thyroid surgery are reliable to predict the onset of PH.

A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [99mTc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71

Introduction: Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods: Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results: A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion: SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only.

Background Accidental ingestion of fish bone is a common cause of otolaryngological emergency. Migration of the ingested bone into the thyroid gland, however, occurs very rarely. The associated clinical presentation, symptoms and duration of discomfort are also highly variable between patients and can be diagnostically challenging. Case presentation Here, we report the case of a 71-year-old female patient presenting with an ingested fish bone that migrated into the right thyroid lobe as a rare cause of suppurative thyroiditis with the clinical features of sepsis. We outline the diagnostic approach, peri- and intraoperative management as well as complications. It is proposed that besides endoscopy, imaging methods such as ultrasound or computed tomography may be necessary to verify the diagnosis and location of an ingested fish bone. Prompt surgical removal of the foreign body and resection of the infectious focus is recommended to minimize the risk of local inflammation, recurrent nerve lesions and septic complications arising from the spread of infection. Conclusion Fish bone migration into the thyroid gland is an extremely rare event, the successful detection and surgical management of which can be achieved through a careful interdisciplinary approach.

Desmoplastic Small Round Cell Tumors (DSRCTs) are an entity of rare, aggressive soft tissue sarcomas described by Gerald and Rosai in 1989. It predominantly affects male adolescents and young adults, with a peak incidence between an age of 20 and 30 years. Typically, DSRCT demonstrate as multiple small tumor nodules within the abdominal cave, retroperitoneum and pelvis. In more than 50% of the cases, the neoplasm presents metastatic at the timepoint of diagnosis. Histologically, DSRCTs have a characteristic morphology with sharply demarcated islands of uniform small round cells in abundant desmoplastic stmma organized in loose extracellular matrix. Immunohistochemistry reveals a polyphenotypic differentiation with co-expression of epithelial, myogenic, mesenchymal and neural markers. The morphology is highly variable and can hinder diagnosis. The most consistent molecular characteristic of DSRCT is the reciprocal t(11;22)(p13q12) translocation. This mutation leads to a formation of the EWSR1-WT1 fusion oncogene, which encodes for a chimeric protein with transcriptional regulatory activity and is regarded as driving source of the disease. To date, there is no standardized concept for clinical management, staging and treatment. Patients receive an aggressive multimodal therapeutic approach consisting of chemotherapy, radical surgical procedures, hyperthermic, intraperitoneal chemotherapy (HIPEC) and radiation. New targeted therapies are used in experimental settings as salvage therapy. So far, none of these therapies showed significant long-term success. This review gives an overview of diagnostic difficulties and pitfalls, discusses therapeutic strategies and highlights options for clinical management.