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.

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.

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.

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.

Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry.

BACKGROUND: Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS: Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION: The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.

Early Postoperative Fasting Serum Glucose Levels are Useful in Depicting Future Diabetes Mellitus in Patients with Curative Insulinoma Surgery.

BACKGROUND: Hyperglycemia has been reported in some patients after curative insulinoma resection but no systematic investigation of glucose metabolism has been shown in a larger cohort of these patients. Therefore, it is still unknown, whether long lasting hyperinsulinism in insulinoma patients induces insulin resistance, which may jeopardize the postoperative health status of these patients. METHODS: Early postoperative fasting serum glucose levels were measured in all insulinoma patients after curative tumor resection during the first 48 h, being operated between 2011 and 2018, retrospectively. RESULTS: Of 77 (100%) patients with benign, spontaneous occuring insulinoma 51 (66.2%) patients were operated on by tumor enucleation. In 15 (19.5%) patients a left pancreatic resection was performed and in 11 (14.3%) patients the pancreatic head or the middle console of pancreatic corpus were excised. In 32 (41.6%) cases the highest fasting postoperative glucose levels were measured between 140-200 mg/dl. In 16 (20.8%) patients the glucose serum levels reached values above 200 mg/dl and in 4 (5.2%) patients short term substitution with insulin was indicated. Only one (1.3%) of these patients developed diabetes mellitus with the need of ongoing insulin treatment. Major postoperative complications were registered in 31 of all 77 patients (40.3%) and in 9 of 16 patients (56.3%) with postoperative glucose levels above 200 mg/dl. This difference was not statistically significant. CONCLUSIONS: Early postoperative (first 48 h) fasting serum glucose levels in insulinoma patients showed significant hyperglycemia above 200 mg/dl in only few patients (20.8%) and chronic postoperative Diabetes mellitus developed in only one of 77 patients (<2%). Therefore, recovery of glucose metabolism after insulinoma resection is fast and medical intervention is not mandatory in most of these patients.

Curative and palliative surgery in patients with neuroendocrine tumors of the gastro-entero-pancreatic (GEP) tract.

The incidence of neuroendocrine tumors (NET) increases with age. Lately, the diagnosis of NET was mainly caused by early detection of small NET (<1 cm) in the rectum and stomach, which are depicted by chance during routine and prophylactic endoscopy. Also in patients with large and metastatic pancreatic and intestinal tumors thorough pathologic investigation with use of different immunohistologic markers discovers more neuroendocrine tumors with low differentiation grade (G2-G3) and more neuroendocrine carcinomas (NEC), nowadays, than in former times. While gastric and rectal NET are discovered as small (<1 cm in diameter) and mainly highly differentiated tumors, demonstrating lymph node metastases in less than 10% of the patients, the majority of pancreatic and small bowel NET have already metastasized at the time of diagnosis. This is of clinical importance, since tumor stage and differentiation grade not only influence prognosis but also surgical procedure and may define whether a combination of surgery with systemic biologic therapy, chemotherapy or local cytoreductive procedures may be used. The indication for surgery and the preferred surgical procedure will have to consider personal risk factors of each patient (i.e. general health, additional illnesses, etc.) and tumor specific factors (i.e. tumor stage, grade of differentiation, functional activity, mass and variety of loco regional as well as distant metastases etc.). Together they define, whether radical curative or only palliative surgery can be applied. Altogether surgery is the only cure for locally advanced NET and helps to increase quality of life and overall survival in many patients with metastatic neuroendocrine tumors. The question of cure versus palliative therapy sometimes only can be answered with time, however. Many different aspects and various questions concerning the indication and extent of surgery and the best therapeutic procedure are still unanswered. Therefore, a close multidisciplinary cooperation of colleagues involved in biochemical and localization diagnostics and those active in various treatment areas is warranted to search for the optimal strategy in each individual patient. How far genetic screening impacts survival remains to be seen. Since surgeons do have a central role in the treatment of NET patients, they have to understand the need for integration into such an interdisciplinary team.

International neuromonitoring study group guidelines 2018: Part II: Optimal recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of surgical, laryngeal, and neural electrophysiologic data.

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.

International neural monitoring study group guideline 2018 part I: Staging bilateral thyroid surgery with monitoring loss of signal.

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.

Indications for the Surgical Management of Benign Goiter in Adults.

BACKGROUND: Thyroidectomy is still three to six times more common in Germany than in the USA, Great Britain, and the Scandinavian countries. Thus, the question is often asked whether thyroidectomy in Germany is being performed for the correct indications. METHODS: This review is based on studies and guidelines containing information on the indications for surgery in benign goiter and Graves' disease; these publications were retrieved by a systematic literature search in the Medline and Cochrane Library databases (1990-2016). The indications recommended here were determined by vote by the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV). RESULTS: On the basis of the available evidence (levels 2-4), and in the absence of prospective studies, the indications for surgery in goiter include a well-founded suspicion of malignancy, local compressive symptoms, and, rarely, cosmesis. In hyperthyroid goiter and Graves' disease, surgery is a potential alternative to radio - iodine therapy, particularly if the volume of the thyroid gland exceeds 80 mL, in patients with advanced or active orbitopathy, and in female patients who are, or plan to be, pregnant. Large, asymptomatic, euthyroid nodular goiter without any suspicion of malignancy and scintigraphically "cold" nodules without any other evidence of malignancy are not indications for surgery. Thyroid operations of higher levels of difficulty (e.g., recurrent goiter, retrosternal extension, Graves' disease) should be carried out in institutions with special expertise in thyroid surgery. CONCLUSION: The decision to operate should be made on an interdisciplinary basis and in conformity with the relevant guidelines after all of the appropriate diagnostic studies have been performed. The radicality of any proposed surgical procedure should be weighed against its potential complications.

Measurement of Basal Serum Calcitonin for the Diagnosis of Medullary Thyroid Cancer.

Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin, basal CT measurement is frequently used for the preoperative diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT) cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114 patients (51 males) were included fulfilling the criteria of an increased preoperative bCT level (>10 pg/ml) and the criteria of an available postoperative histology analysis. Based on a ROC plot analysis, the cut-off values for the diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were identified. The most precise bCT thresholds for the identification of MTC were ≥46 pg/ml for males (sensitivity: 93.6%, specificity: 95.0%, PPV: 97%, NPV: 90%) and ≥35 pg/ml for females (sensitivity: 87.3%, specificity: 87.5%, PPV: 98%, NPV: 50%). Using these cut-offs, only 6% of male patients were not identified of having MTC, whereas 5% were false positive (having instead C cell hyperplasia). In females, the discrepancy was higher since 13% of female MTC patients were false negative by using the cut-off of ≥35 pg/ml, and 13% had false positive results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the identification of MTC vs. C cell hyperplasia and non-malignancy were defined, which can be used in clinical routine. In female patients, however, the accuracy is much lower compared to males.

Total Parathyroidectomy With Routine Thymectomy and Autotransplantation Versus Total Parathyroidectomy Alone for Secondary Hyperparathyroidism: Results of a Nonconfirmatory Multicenter Prospective Randomized Controlled Pilot Trial.

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.