First effectiveness data of lenvatinib and pembrolizumab as first-line therapy in advanced anaplastic thyroid cancer: a retrospective cohort study.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive neoplasm. We still lack effective treatment options, so survival rates remain very low. Here, we aimed to evaluate the activity of the combination of lenvatinib and pembrolizumab as systemic first-line therapy in ATC. METHODS: In a retrospective analysis, we investigated the activity and tolerability of combined lenvatinib (starting dose 14 to 24 mg daily) and pembrolizumab (200 mg every three weeks) as first-line therapy in an institutional cohort of ATC patients. RESULTS: Five patients with metastatic ATC received lenvatinib and pembrolizumab as systemic first-line therapy. The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At the first follow-up, one patient had partial response, three patients had stable disease, and one patient was formally not evaluable due to interference of assessment by concomitant acute infectious thyroiditis. This patient was then stable for more than one year and was still on therapy at the data cutoff without disease progression. Further analyses revealed deficient DNA mismatch repair, high CD8+ lymphocyte infiltration, and low macrophage infiltration in this patient. Of the other patients, two had progressive disease after adverse drug reactions and therapy de-escalation, and two died after the first staging. For all patients, the PD-L1 combined positive score ranged from 12 to 100%. CONCLUSIONS: The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long-lasting response. However, we could not confirm the exceptional responses for this combination therapy reported before in pretreated patients.

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.

For the histopathological work-up of resected neuroendocrine tumors of the small intestine (siNET), the determination of lymphatic (LI), microvascular (VI) and perineural (PnI) invasion is recommended. Their association with poorer prognosis has already been demonstrated in many tumor entities. However, the influence of LI, VI and PnI in siNET has not been sufficiently described yet. A retrospective analysis of all patients treated for siNET at the ENETS Center of Excellence Charité-Universitätsmedizin Berlin, from 2010 to 2020 was performed (n = 510). Patients who did not undergo primary resection or had G3 tumors were excluded. In the entire cohort (n = 161), patients with LI, VI and PnI status had more distant metastases (48.0% vs. 71.4%, p = 0.005; 47.1% vs. 84.4%, p < 0.001; 34.2% vs. 84.7%, p < 0.001) and had lower rates of curative surgery (58.0% vs. 21.0%, p < 0.001; 48.3% vs. 16.7%, p < 0.001; 68.4% vs. 14.3%, p < 0.001). Progression-free survival was significantly reduced in patients with LI, VI or PnI compared to patients without. This was also demonstrated in patients who underwent curative surgery. Lymphatic, vascular and perineural invasion were associated with disease progression and recurrence in patients with siNET, and these should therefore be included in postoperative treatment considerations.

Endoscopic ultrasound-guided ethanol ablation versus surgical resection of insulinomas.

PURPOSE: Insulinoma is a rare tumor of the pancreas that can lead to hypoglycemia. To date, the standard therapy is surgical resection. After the first case report of successful endoscopic ultrasound-guided (EUS) ethanol injection 16 years ago, the need for establishing an alternative treatment method remains unchanged given the high morbidity rates of surgery and its unsuitability in some patients. MATERIALS AND METHODS: Here, we provide retrospective data from 33 insulinoma patients that were treated at our center between 2010 and 2021. Of these, 9 patients were treated with EUS-guided ethanol injection and 24 underwent pancreatic surgery. RESULTS: The ethanol group was older (ethanol: mean ± SE 67.8±11.2 years vs. surgery: 52.3±15.7, p=0.014) with a higher Charlson Comorbidity Index (3.0 (1.0;4.0) vs. 1.0 (0.0;2.0), p=0.008). The lowest glucose values were similar between groups before (ethanol: 2.09±0.17 mmol/l vs. surgery: 1.81±0.08, p=0.158) and after (4.95±0.74 vs. 5.41±0.28, p=0.581) the respective treatments. Complications occurred more frequently in the surgery group (11 % vs. 54 %, p=0.026). One patient after prior partial pancreatectomy died postoperatively. The hospitalization time was significantly shorter in the ethanol group (4.78±0.78 days vs. 19.88±4.07, p<0.001). CONCLUSION: EUS-guided ethanol injection can be similarly effective for the treatment of hyperinsulinemic hypoglycemia compared with pancreatic surgery but seems to be associated with less severe complications. This implies the need for prospective randomized trials in insulinoma patients with a low risk for malignancy.

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients.

BACKGROUND: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. METHODS: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. RESULTS: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DISCUSSION: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors.

PURPOSE: Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. METHODS: Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. RESULTS: A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. CONCLUSION: Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.

[Special features of the diagnostics and treatment of hereditary primary hyperparathyroidism]. / Besonderheiten in Diagnostik und Therapie des hereditären primären Hyperparathyreoidismus.

Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of 40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type 1 (MEN-1) or show germline mutations of the MEN­1 gene. Currently, germline mutations that lead to a specific diagnosis in patients with hpHPT have currently been described in 13 different genes, which enables a clear diagnosis of the disease; however, a clear genotype-phenotype correlation does not exist, even though the complete loss of a coded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.

Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center.

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité-Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.

[Surgery of hyperparathyroidism]. / Chirurgie des Hyperparathyreoidismus.

The surgical removal of diseased parathyroid glands is the only curative treatment for primary and secondary hyperparathyroidism. Before an intervention, the confirmed diagnosis and an accurate localization are decisive for selection of the appropriate procedure. After appropriate localization diagnostics, a focussed intervention is possible for primary hyperparathyroidism, whereby every intervention must be controlled by intraoperative monitoring of parathyroid hormone. Reoperations or multiple glandular disease necessitate a differentiated approach with appropriate prior diagnostics.

[Differentiated Strategies for the Therapy of Liver Metastases in Gastro-entero-pancreatic Neuroendocrine Neoplasia]. / Differenzierte Therapiestrategie bei Lebermetastasen gastro-entero-pankreatischer Neuroendokriner Neoplasien.

Neuroendocrine neoplasias comprise a heterogenous group of malignant tumours, mostly arising from the gastro-entero-pancreatic system (GEP). Most of these tumours develop from the small intestine and pancreas and the liver is the predominant site for distant metastases. Patients may be asymptomatic for a long time and liver metastases are frequently diagnosed by chance or during operations for bowel obstruction, for example, during emergency surgery. The only curative therapy consists in complete removal of primary and metastases. In case of metastatic disease, various treatment modalities need to be discussed in interdisciplinary tumour boards comprised of specialists from gastroenterology, (liver-)surgery, radiology, nuclear medicine, radiotherapy, pathology and endocrinology. By combining different therapies, even patients with progressive disease may reach long-term overall survival with good quality of life. The most important factors for decisions on therapy are individual factors like tumour grading, hormonal functionality, type of metastases and evolution of the disease. Adequate treatment of liver metastases comprises various surgical strategies as well as locally ablative radiological interventions and nuclear medical therapies, in complement to systemic treatments.

Hyperkalemia Following Parathyroidectomy in Patients with Renal Hyperparathyroidism-New Thresholds for Urgent Perioperative Dialysis.

Parathyroidectomy (PTX) is a mainstay of treating secondary hyperparathyroidism (SHPT) in patients with kidney failure in order to reduce the incidence of cardiovascular events (CVE), increase overall survival and improve quality of life. Perioperative hyperkalemia may lead to devastating cardiac complications. Distinct preoperative thresholds for serum potassium levels (SPL) were defined, but neither their usefulness nor consecutive risks are understood. This study compared the results and efficacy of different clinical procedures in preventing or treating perioperative hyperkalemia, including postoperative urgent hemodialysis (UHD). Methods: Patients from Charité-Universitätsmedizin Berlin and Rheinland Klinikum Lukaskrankenhaus, Neuss, undergoing PTX due to SHPT between 2008 and 2018 were analyzed retrospectively with regard to demographic parameters, surgery specific conditions and perioperative laboratory results. Comparisons of patient values from both centers with focus on perioperative hyperkalemia and the need for UHD were performed. Results: A total of 251 patients undergoing PTX for SHPT were included (Neuss: n = 121 (48%); Berlin: n = 130 (52%)). Perioperative hyperkalemia (SPL ≥ 5.5 mmol/L) was noted in 134 patients (53%). UHD on the day of surgery was performed especially in patients with intraoperative hyperkalemia, in females (n = 40 (16%) vs. n = 27 (11%); p = 0.023), in obese patients (n = 27 (40%) vs. n = 50 (28%), p = 0.040) and more often in patients treated in Neuss (n = 42 (35%) vs. 25 (19%); p = 0.006). For patients treated in Neuss, the intraoperative hyperkalemia cut-off level above 5.75 mmol/L was the most predictive factor for UHD (n = 30 (71%) vs. n = 8 (10%); p < 0.001). Concerning secondary effects of hyperkalemia or UHD, no patient died within the postoperative period, and only three patients suffered from acute CVE, with SPL > 5.5 mmol/L measured in only one patient. Conclusion: Perioperative values could not predict postoperative hyperkalemia with the need for UHD. Previously defined cut-off levels for SPL should be reconsidered, especially for patients undergoing PTX. Early postoperative dialysis in patients with postoperative hyperkalemia can be performed with a low risk for complications and may be indicated for all patients with increased perioperative SPL.

The challenge to differentiate between sarcoma or adrenal carcinoma-an observational study.

BACKGROUND: Adrenal sarcomas are rare malignant tumors with structural and clinical similarities to sarcomatoid adrenocortical carcinoma. Preoperative diagnosis of tumors of the adrenal gland can be challenging and often misleading thus detaining patients from appropriate oncological strategies. OBJECTIVE: This analysis of a case series evaluated the predictive capability of the primary clinical diagnosis in case of malignancies of the adrenal gland. METHODS: Thirty two patients were treated from 2009 to 2015 at our clinic and analyzed retrospectively. All patients had computed tomography and/or magnet resonance imaging and a primary histopathological examination at our institution after surgery. Ten questionable cases were surveyed by a reference pathologist. RESULTS: Twelve out of 32 diagnoses had to be revised (37.5%). Only 15 out of 24 tumors primarily classified as adrenocortical carcinoma were finally described as primary adrenal cancer. We found two leiomyosarcomas, one liposarcoma, one sarcomatoid adrenocortical carcinoma, and one epitheloid angiosarcoma among 12 misleading diagnoses. Other tumors turned out to be metastases of lung, hepatocellular, and neuroendocrine tumors. Larger tumors were significantly more often correctly diagnosed compared to smaller tumors. Four patients of the group of revised diagnoses died whereas all patients with confirmed diagnoses survived during the follow-up. CONCLUSION: Preoperative assessment of tumors of the adrenal gland is still challenging. In case of wrong primary diagnosis, the prognosis could be impaired due to inadequate surgical procedures or insufficient preoperative oncological treatment.

Automatized Hepatic Tumor Volume Analysis of Neuroendocrine Liver Metastases by Gd-EOB MRI-A Deep-Learning Model to Support Multidisciplinary Cancer Conference Decision-Making.

BACKGROUND: Rapid quantification of liver metastasis for diagnosis and follow-up is an unmet medical need in patients with secondary liver malignancies. We present a 3D-quantification model of neuroendocrine liver metastases (NELM) using gadoxetic-acid (Gd-EOB)-enhanced MRI as a useful tool for multidisciplinary cancer conferences (MCC). METHODS: Manual 3D-segmentations of NELM and livers (149 patients in 278 Gd-EOB MRI scans) were used to train a neural network (U-Net architecture). Clinical usefulness was evaluated in another 33 patients who were discussed in our MCC and received a Gd-EOB MRI both at baseline and follow-up examination (n = 66) over 12 months. Model measurements (NELM volume; hepatic tumor load (HTL)) with corresponding absolute (ΔabsNELM; ΔabsHTL) and relative changes (ΔrelNELM; ΔrelHTL) between baseline and follow-up were compared to MCC decisions (therapy success/failure). RESULTS: Internal validation of the model's accuracy showed a high overlap for NELM and livers (Matthew's correlation coefficient (φ): 0.76/0.95, respectively) with higher φ in larger NELM volume (φ = 0.80 vs. 0.71; p = 0.003). External validation confirmed the high accuracy for NELM (φ = 0.86) and livers (φ = 0.96). MCC decisions were significantly differentiated by all response variables (ΔabsNELM; ΔabsHTL; ΔrelNELM; ΔrelHTL) (p < 0.001). ΔrelNELM and ΔrelHTL showed optimal discrimination between therapy success or failure (AUC: 1.000; p < 0.001). CONCLUSION: The model shows high accuracy in 3D-quantification of NELM and HTL in Gd-EOB-MRI. The model's measurements correlated well with MCC's evaluation of therapeutic response.

Insulinoma in pregnancy (a case presentation and systematic review of the literature).

Insulinomas are rare, benign and functional tumors that coincidentally may become overt during pregnancy or in the post-partum period. As the general symptoms of a pregnancy might cover the clinical presentation, diagnosing remains challenging. We present one additional case of a post-partum insulinoma, combined with a systematic review of the literature to sum up relevant details in diagnosis and treatment. A systematic request of Pubmed/Medline was conducted using the following terms: "insulinoma AND pregnancy" and "insulinoma" for a second request of ClinicalTrials.gov. All publications concerning pregnant or post-partum women with insulinoma were included. Thirty-six cases could be identified for analysis. Each publication was reviewed for demographic, diagnostic and therapeutic data. The most frequent clinical signs were unconsciousness and neurological symptoms. 64.9% were diagnosed during early pregnancy and 35.1% post-partum. 91.9% underwent surgery with a third resected during pregnancy without severe influence on fetal or maternal outcome. Three patients died of metastatic disease or misdiagnosing, two of them miscarried. Insulinoma in pregnancy is rare but should be considered in case of unclear hyperinsulinemic hypoglycemia. Surgery can be performed during the second trimester or post-partum with promising outcome.

Multiple liver perforations: complication of an outpatient liposuction procedure.

We report on a 29-year-old woman who presented with abdominal right upper quadrant pain after an outpatient liposuction procedure. A contrast-enhanced computed tomography scan revealed 4 hepatic perforation tracts with subcapsular liver hematoma and hematoperitoneum. The patient was treated by intravenous tranexamic acid and isotonic fluids and monitored on an intensive care unit. No intervention or surgery was necessary during her hospital stay. Follow-up imaging after 3 days using contrast-enhanced ultrasound still showed the perforation tracts in the liver but no expansion of subcapsular hematoma. After 7 days, the patient was discharged home with stable hemoglobin and reduced pain. Liver perforation is a rare complication of liposuction procedures. In patients with abdominal pain after liposuction, contrast-enhanced imaging studies should be performed to identify and characterize solid organ injury. Teams with expertise in angiography and visceral surgery need to be on standby.

A rare case of a patient with a high grade neuroendocrine tumor developing neutropenic sepsis after receiving PRRT combined with Capecitabine or Temozolomide: A case report.

Neuroendocrine tumors (NET) are rare and demonstrate variable clinical behavior depending on the degree of tumor differentiation. Patients with poorly differentiated tumors (NET G3) have a poor prognosis. Systemic treatment with cytotoxic chemotherapy is considered to be the treatment of choice. In patients that are refractory or intolerant to first-line therapy, experts recommend peptide receptor radionuclide therapy (PRRT) in tumors that express somatostatin receptors. Recently, combinations of PRRT and chemotherapy were tested in patients with NET. Available data have reported promising tumor control rates and an excellent toxicity profile in cases where PRRT had been administered with capecitabine/temozolomide, even when administered as salvage therapy. The current study reported an exceptional case of advanced NET G3 with severe toxicity upon receiving PRRT in combination with capecitabine/temozolomide as third line therapy. The patient developed a life-threatening neutropenic fever, fungal pneumonia and necrotizing mastitis 23 days after the first cycle of therapy was administered. However, the treatment led to a significant reduction in tumor size. A total of 5 months after treatment initiation, the patient was alive and in excellent clinical condition with sustained tumor response. In summary, the current study presented a rare case of high grade NET exhibiting an almost complete response to PRRT in combination capecitabine/temozolomide, despite facing unexpected severe toxicity.

Influence of Parathyroidectomy on Kidney Graft Function in Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: Timing of parathyroidectomy (PTX) remains controversial in candidates for kidney transplant with concomitant renal hyperparathyroidism (HPT). The aim of this retrospective study was to identify the influence of early vs late posttransplant PTX compared to pretransplant PTX on renal graft function and morbidity. METHODS: This single-center cohort study includes 57 patients with renal HPT and kidney transplantation treated between 2007 and 2017. Ninety-six patients had surgery for renal HPT between 2007 and 2017 as a consecutive sample. Group 1 (n = 30; tertiary HPT), group 2 (n = 66; secondary HPT). Of group 1, 4 patients were excluded for PTX before and after kidney transplantation. In group 2, 20 patients were excluded since they had not undergone kidney transplantation during follow-up. Twelve patients were excluded because of short follow-up (kidney transplantation in 2018), and 3 patients were excluded because of transplant failure within 90 days. Twenty-six patients underwent posttransplant PTX (10 patients within 12 months after transplant), and 31 patients had undergone PTX prior to kidney transplantation. Graft function, serum calcium concentrations, parathyroid hormone (PTH) levels, postoperative morbidity, and 90-day mortality were recorded. RESULTS: Median age was 53.1 years in group 1 and 49.1 years in group 2. Most patients were male (53.8% in group 1; 54.8% in group 2). Median preoperative PTH levels were significantly different with 331.6 pg/mL in group 1 and 667.5 pg/mL in group 2 (P = .003). Creatinine levels changed little from 1.4 mg/dL (range, 0.8-2.5) to 1.7 mg/dL (range, 0.7-7.3) in group 1, and no difference was seen between early or late PTX after transplantation. In group 2, creatinine levels were 8.5 mg/dL (range, 4.6-11.7) before PTX and 8.7 mg/dL (range, 5.1-11.9) after PTX. We saw no correlation between postoperative PTH and kidney function. Thirty-five patients with postoperative PTH < 15 pg/mL displayed a mean postoperative creatinine of 5.5 mg/dL (range, 4.3-6.8), similar to other patients. Both the 30-day and 90-day mortality rates were zero. CONCLUSIONS: PTX had no negative effect on graft function, whether performed before or after (early or late) kidney transplantation. Surgical cure of renal HPT should be performed as soon as possible to prevent secondary complications and can also be safely carried out early after transplantation.

Influence of Gender on Therapy and Outcome of Neuroendocrine Tumors of Gastroenteropancreatic Origin: A Single-Center Analysis.

INTRODUCTION: Gender-specific treatment is gaining growing attention in various fields of medicine. In gastrointestinal cancer, influence of sex on outcome has been discussed, while this has not been the case in neuroendocrine tumors. Overall, the incidence of neuroendocrine neoplasms is rising, especially for appendiceal neuroendocrine neoplasms in women. Also, women seem to have a slight advantage in response to therapy, especially for liver metastases. OBJECTIVES: This single-center analysis aimed to investigate gender-specific differences in our cohort related to distribution, therapy, and outcome. METHODS: Patients from the NET registry as well as the clinic database were evaluated retrospectively concerning overall survival and response to therapy with respect to gender. A subgroup analysis was carried out for patients with low grading and response to chemotherapy, as well as for patients with good and moderate grading receiving peptide receptor radionuclide therapy and for a group of patients with liver surgery. RESULTS: No specific differences could be detected for overall survival or response to therapy between male and female patients. Mean survival was estimated with 242.2 months (±10.39 SD) altogether and 221.7 months (± 13.02 SD) for male patients and 253.5 months (±15.24 SD) for female patients from the NET registry from initial diagnosis. There was no significant difference between female and male patients (p = 0.136). For patients receiving chemotherapy, overall survival from initial diagnosis was calculated with 26 months (±2.59) and did not show any significant differences between female and male patients 24.8 months (±2.81 SD) vs. 27.8 months (±3.86 SD, p = 0.87). Patients undergoing peptide receptor radionuclide therapy showed a median progression-free survival of 26.9 months (±2.82 SD), with 16.9 (±5.595 SD) and 26.9 months (±3.019 SD) for male and female patients, respectively (p = 0.2). In the group of patients with liver surgery, female patients reached an estimated overall survival of 64.7 months (±4.16 SD), male patients 65.1 months (±2.79 SD, p = 0.562). CONCLUSION: Our cohort did not reveal significant differences in outcome and response to therapy with regards to gender.

Is There a Gender Difference in Clinical Presentation of Renal Hyperparathyroidism and Outcome after Parathyroidectomy?

INTRODUCTION: Gender has been proven to influence the pathophysiology and treatment of numerous diseases, including kidney diseases and hormonal dysfunction like hyperparathyroidism. Thus, higher parathormone levels have been demonstrated in women with end-stage kidney disease, when compared to men. OBJECTIVES: We questioned whether female gender is associated with an increased risk for parathyroid nodular hyperplasia and necessary parathyroidectomy in dialysis patients and assessed demographics as well as outcome data for women and men undergoing parathyroidectomy for renal hyperparathyroidism. PATIENTS AND METHODS: One hundred and thirty patients (men = 75, female = 55) with end-stage renal disease on chronic dialysis and advanced secondary hyperparathyroidism who underwent parathyroidectomy between 2008 and 2014 at our center were analyzed retrospectively. Perioperative characteristics and short-term outcome were evaluated with respect to biological gender. RESULTS: No differences could be demonstrated for patient demography, comorbidities and the perioperative course between males and females. Only preoperative calcium levels were lower in female than in male patients (2.3 ± 0.19 vs. 2.3 ± 0.26, p = 0.04). There were more women, however, with cerebrovascular complications during follow-up (p = 0.04). There was no postoperative mortality, and all complications and comorbidities with exception of cerebrovascular diseases were equally distributed between female and male patients. CONCLUSION: Overall, we could not demonstrate many significant differences between male and female patients with end-stage renal diseases, chronic dialysis and operated secondary hyperparathyroidism. Only preoperative electrolyte levels were higher in male than in female patients, and cerebrovascular complications developed more often in females than in males during long-term follow-up.