Objective The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).Methods We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).Results In PPGLs, estradiol and progesterone (1 mu m) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ER alpha) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ER alpha-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 mu m) displayed no effects, but higher doses of testosterone (10 mu m) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.Conclusion We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ER alpha positivity.

STUDY AIMS:Abdominal and retroperitoneal sarcomas are rare and heterogeneous. Despite a considerable number of sarcoma centres in Switzerland, only very limited data is available regarding clinical outcomes after primary surgical treatment. In this study, we retrospectively analysed a cohort of 157 patients treated at a Swiss sarcoma centre, aiming to assess whether the clinical outcomes in our cohort are comparable to those reported by international centres. METHODS:Overall, 271 patients with abdominal and retroperitoneal sarcomas, treated between January 2012 and December 2022, were available. Patients with malignant disease and primary resection were included. The primary endpoint was overall survival, while secondary endpoints included disease-free survival, incidence of histological subtypes, completeness of surgical resection and tumour rupture. RESULTS:Ultimately 157 patients with primary, resectable soft tissue sarcoma were included in the analysis. Median follow-up after surgery was 52.6 months (95% confidence interval [CI]: 42.24-62.95). Median overall survival was 87.9 months (95% CI: 54.95-120.74); by subgroup, 117.5 months for gastrointestinal stroma tumour (95% CI: 76.96-158.00), 61.8 months for liposarcoma (95% CI: 40.16-83.36), 117.8 months for leiomyosarcoma (95% CI not achieved) and 100.2 months for other rare subtypes (95% CI: 59.65-111.30). Forty-four (28%) patients developed tumour recurrence. CONCLUSIONS:Overall outcomes in this series are comparable to those from large international registries. A national data registry might help to improve reporting of clinical data and assure quality of care of Swiss sarcoma patients.

Background/Objectives: ABO-incompatible live-donor kidney transplantation (ABOi-LDKT) has become an established treatment for end-stage renal disease. Non-inferiority in the long-term graft function compared to ABO-compatible live-donor kidney transplantations (ABOc-LDKTs) has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to ABOi-LDKTs has not yet been quantified. The aim of this study was to determine if ABOi-LDKT recipients suffer from additional morbidity and whether the resulting burden is justified. Methods: We retrospectively analyzed 45 matched pairs of ABOi-LDKTs and ABOc-LDKTs transplanted over a twenty-year period from January 2000 to March 2020. The number and duration of postoperative readmissions, surgical complication rates according to Clavien-Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new-onset diabetes, and infections as well as tumor incidence were analyzed. Results: Patient and graft survival, as well as graft function, were comparable between the two groups. There were no significant differences in terms of complications, readmission rates, and length of readmission, as well as infection and rejection rates. The median CCIs for ABOi-LDKTs and ABOc-LDKTs at primary discharge and 3, 6, 12, and >12 months were 20.9 vs. 20.9 (p = 0.363), 31.4 vs. 33.7 (p = 0.438), 33.7 vs. 33.7 (p = 0.875), 20.9 vs. 33.1 (p = 0.25), and 27.1 vs. 31.9 (p = 0.163), respectively. Conclusions: ABOi-LDKT seems safe, with comparable outcome, complication, and readmission rates to ABOc-LDKT. In recipients with ABOi living donors, transplantation should not be delayed solely due to concerns over increased perioperative risks.

BACKGROUND:Liver transplantation (LT) for neuroendocrine liver metastases (NELM) is still in debate. Studies comparing LT with liver resection (LR) for NELM are scarce, as patient selection is heterogeneous and experience is limited. The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.DATA SOURCES:A scoping literature search on LT and LR for NELM was performed with PubMed, including English articles up to March 2023.RESULTS:International guidelines recommend LR for NELM in resectable, well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies. Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival. In highly selected patients (based on the Milan criteria) with unresectable NELM, oncologic results of LT are promising. Prognostic factors include tumor biology (G1/G2) and burden, waiting time for LT, patient age and extrahepatic spread. Based on low-level evidence, LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR. The benefits of LT were lost in patients beyond the Milan NELM-criteria.CONCLUSIONS:With adherence to strict selection criteria especially tumor biology, LT for NELM is becoming a valuable option providing oncologic benefits compared to LR. Recent evidence suggests even stricter selection criteria with regard to tumor biology.

PURPOSE:To investigate the differences in the visibility and size of abdominal wall hernias in computed tomography (CT) with and without Valsalva maneuver. METHODS:This single-center retrospective study included consecutive patients who underwent abdominal CTs with Valsalva maneuver between January 2018 and January 2022. Inclusion criteria was availability of an additional non-Valsalva CT within 6 months. A combined reference standard including clinical and surgical findings was used. Two independent, blinded radiologists measured the hernia sac size and rated hernia visibility on CTs with and without Valsalva. Differences were tested with a Wilcoxon signed rank test and McNemar's test. RESULTS:The final population included 95 patients (16 women; mean age 46 ± 11.6 years) with 205 hernias. Median hernia sac size on Valsalva CT was 31 mm compared with 24 mm on non-Valsalva CT (p < 0.001). In 73 and 82% of cases, the hernias were better visible on CT with Valsalva as compared to that without. 14 and 17% of hernias were only visible on the Valsalva CT. Hernia visibility on non-Valsalva CT varied according to subtype, with only 0 and 3% of umbilical hernias not being visible compared with 43% of femoral hernias. CONCLUSIONS:Abdominal wall hernias are larger and better visible on Valsalva CT compared with non-Valsalva CT in a significant proportion of patients and some hernias are only visible on the Valsalva CT. Therefore, this method should be preferred for the evaluation of abdominal wall hernias.

The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95

Multimodal therapy for peritoneal metastasis (PM) including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provides long-term survival in highly selected colorectal cancer patients. Mechanisms behind HIPEC are unknown and may include induction of adaptive immunity. We therefore analyzed human PM samples and explored the impact of HIPEC in experimental models. Human samples from colorectal primary tumors (n = 19) and PM lesions (n = 37) were examined for the presence of CD8 + T-cells and their association with disease free (DFS) and overall survival (OS). CD8 + T cell response after HIPEC was assessed using an in-vivo PM mouse model, tumor cell lines and patient-derived tumor organoids. Patients with high intraepithelial CD8 + T cell counts showed longer DFS and OS. In the mouse model, HIPEC controlled growth of PM and increased numbers of functional granzyme positive CD8 + T cells within tumors. Cell lines and human organoids that were treated with heated chemotherapies showed immunogenic changes, reflected by significantly higher levels of MHC-class I molecules and expression of Cancer Testis Antigens Cyclin A1 and SSX-4. Using in-vitro co-culture assays, we noticed that cancer cells treated with heated chemotherapy primed dendritic cells, which subsequently enhanced effector functions of CD8 + T cells. The presence of CD8 + T-cells within PM lesions is associated with prolonged survival of patients with PM. Data from PM mouse model and in-vitro assay show that heated chemotherapies induce immunogenic changes on cancer cells leading to induction of CD8 + T-cells mediated immunity, which seems to control growth of PM lesions in mice after HIPEC.

CONTEXT:Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (PPGLs) are still limited. In recent years, antitumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs. OBJECTIVE:Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines. METHODS:We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at 2 centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed. RESULTS:We found opposing effects of 5 µM CBD: significant antitumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of antitumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (P = .042). Of the cluster 2-related tumors, NF1 PPGLs showed the strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant antitumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures and significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures. CONCLUSION:We suggest a potential novel treatment option for some NETs/PPGLs but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients and possibly as health supplements.

In patients with locally advanced (LAPC) or borderline resectable (BRPC) pancreatic cancer, primary chemotherapy with or without radiotherapy is recommended for local downstaging to enable a potentially curable resection.FOL-FIRINOX or gemcitabine-based chemotherapy are in common use.However, it is currently unclear what chemotherapy should be preferred for patients with LAPC and BRPC.][3][4]

BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

The liver is a common site of metastases from many cancers, particularly those originating in the gastrointestinal tract. Liver transplantation is an uncommonly used but promising and at times controversial treatment option for neuroendocrine and colorectal liver metastases. Transplantation with meticulous patient selection has been associated with excellent long-term outcomes in individuals with neuroendocrine liver metastases, but questions remain regarding the role of transplantation in those who could also be eligible for hepatectomy, the role of neoadjuvant/adjuvant treatments in minimising recurrence, and the optimal timing of the procedure. A prospective pilot study of liver transplantation for unresectable colorectal liver metastases that reported a 5-year overall survival rate of 60% reinvigorated interest in this area following initially dismal outcomes. This has been followed by larger studies, and prospective trials are ongoing to quantify the potential benefits of liver transplantation over palliative chemotherapy. This review provides a critical summary of currently available knowledge on liver transplantation for neuroendocrine and colorectal liver metastases, and highlights avenues for further study to address gaps in the evidence base.

Abstract Background Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. Methods Patients were included in this retrospective single-center analysis from 2012—2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. Results Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 – 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 – 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 – 2.89; log-rank test, p < 0.001). Conclusion This retrospective analysis presents a great overview of all patients’, disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients’ selection for upcoming clinical prospective studies.

AIM: Haemophilic pseudotumours are complications in patients with haemophilia A or B and result from locally repetitive bleeding, mainly in the musculoskeletal system. Abdominal haemophilic pseudotumours are exceptionally rare but may cause severe complications. This systematic review aimed to evaluate therapy strategies for symptomatic abdominal haemophilic pseudotumours. METHODS: We systematically searched three databases (Medline [PubMed], Web of Science and EMBASE) for publications published between 1995 and 2023. Two reviewers independently selected the studies, extracted data and performed a quality assessment using the JBI critical appraisal checklist. RESULTS: From a total of 1199 articles, 39 articles describing 41 cases were included for final analysis. Conservative or interventional treatment was performed in 12 cases. In eight cases, a step-up to surgical therapy after interventional treatment was indicated. Primary surgical therapy was performed in 21 cases. Failure to cure was documented in 50% (n = 6) of patients treated in the first group, with a mortality rate of 16.6% (n = 2). Interventional therapy with a step-up to surgery showed no morbidity or mortality. Primary surgical resection documented favourable results in 66.6% (n = 14), with failure to cure in 9.5% (n = 2) and a mortality rate of 14.3% (n = 3). CONCLUSION: Primary surgical resection can be a first-line therapy for symptomatic, abdominal haemophilic pseudotumours, whereas preoperative embolisation could be used as a bridging therapy before surgery, especially in emergency settings. Diagnostic biopsy and percutaneous drainage should be avoided to prevent complications.

BackgroundEmergency resection is common for malignant right-sided obstructive colon cancer. As there is evidence showing a potential benefit of self-expandable metal stents as a bridge to surgery, a new debate has been initiated.ObjectiveThe aim of this study was to compare self-expandable metal stents with emergency resection in right-sided obstructive colon cancer.Data sourceA systematic search was conducted accessing Medline/PubMed, Scopus, Embase, and the Cochrane Database of Systematic Reviews.Study selectionStudies reporting either emergency surgery or stent placement in right-sided obstructive colon cancer were included.InterventionStent or emergency resection in right-sided obstructive colon cancer.Main outcome measuresMorbidity rate, mortality rate, stoma rate, laparoscopic resection rate, anastomotic insufficiency rate, success rate of stent.ResultsA total of 6343 patients from 16 publications were analyzed. The stent success rate was 0.92 (95% CI, 0.87 to 0.95) with perforation of 0.03 (95% CI, 0.01 to 0.06). Emergency resection was performed laparoscopically at a rate of 0.15 (95% CI, 0.09 to 0.24). Primary anastomosis rate in emergency resection was 0.95 (95% CI, 0.91 to 0.97) with an anastomotic insufficiency rate of 0.07 (95% CI, 0.04 to 0.11). The mortality rate after emergency resection was 0.05 (95% CI, 0.02 to 0.09). Primary anastomosis and anastomotic insufficiency rate were similar between the two groups (RR: 1.02; 95% CI, 0.95 to 1.1; p = 0.56 and RR: 0.53; 95% CI, 0.14 to 1.93; p = 0.33). The mortality rate in emergency resection was higher compared to stent (RR: 0.51, 95% CI 0.30 to 10.89, p = 0.016).LimitationNo randomized controlled trials are available.ConclusionStent is a safe and successful alternative to emergency resection and may increase the rate of minimally invasive surgery. Emergency resection, however, remains safe and did not result in higher rate of anastomotic insufficiency. Further high-quality comparative studies are warranted to assess long-term outcomes.

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored. We investigated the expression of the hypoxia-marker HIF-2α and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2α and checkpoint inhibitors. A total of 29 tumor samples from 25 patients who were operated at a single center were included and analyzed utilizing immunohistochemistry (IHC) for PD-L1 and HIF-2α. Embolization prior to surgery was performed in seven (24%) tumors. PD-L1 expression in tumor cells of head and neck paragangliomas (HNPGLs) receiving prior embolization (median PD-L1 positivity: 15%) was significantly higher as compared to PD-L1 expression in HNPGLs without prior embolization (median PD-L1 positivity: 0%) (p = 0.008). Consistently, significantly more HNPGLs with prior embolization were positive for HIF-2α (median nuclear HIF-2α positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2α positivity: 0%) (p = 0.016). Our results support the hypothesis that embolization with subsequent hypoxia leads to the upregulation of both PD-L1 and HIF-2α in HNPGLs, and could thus facilitate targeted treatment with HIF-2α and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease.

Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents.

Context Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. Objective Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. Methods Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs. Results Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx). Conclusion SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.

Abstract Background AB0 incompatible kidney transplantation has become a genuine treatment for end-stage renal disease. Non-inferiority in long term graft function compared to AB0 compatible transplantation has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to AB0 incompatible transplantation has not yet been quantified. Aims The aim of the study was to determine if AB0 incompatible recipients have additional morbidity and whether this burden is justified or whether kidney paired donation programs should be advocated. Methods From January 2000 to March 2020 46 AB0 incompatible living kidney transplantations were performed. Patients were matched with AB0 compatible recipients according to sex, age, underlying disease, year of transplantation, and duration of dialysis. Number and duration of readmissions, surgical complication rates according to Clavien-Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new onset diabetes, as well as tumor incidence were analyzed. Results Readmission rate was not higher in AB0 incompatible recipients. The median difference in length of hospital stay for readmissions, CCI during primary hospital stay, and CCI for readmissions at 3, 6, 12 and >12 months after transplantation were comparable. Incidence of tumor and new onset diabetes after transplantation was not increased in incompatible recipients. Conclusions AB0 incompatible recipients do not suffer from a higher burden compared to AB0 compatible recipients. We currently recommend not delaying transplantation in AB0 incompatible pairs.

BACKGROUND:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC.METHODS:Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria.RESULTS:Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific - although less sensitive - marker to diagnose infectious complications after CRS/HIPEC.DISCUSSION/CONCLUSION:Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.