[Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. / Lokale Resektion von neuroendokrinen Tumoren des Dünndarms (SI-NEN) : Aktuelle Prinzipien.

BACKGROUND: Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS: Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS: Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION: Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.

Surgical aspects related to hereditary pancreatic cancer.

The goal of surveillance programs for individuals at risk (IAR) from familial pancreatic cancer (FPC) families or families with other inherited tumor syndromes predisposing to the development of pancreatic adenocarcinoma (PDAC), such as hereditary pancreatitis or Peutz-Jeghers syndrome, is the dectection and consecutive curative resection of early PDAC or even better its high-grade precursor lesions. Although the indication for surgery is quite established, the extent of surgery is not well defined due to the lack of evidence-based data. In addition, multiple factors have to be taken into account to determine an optimal personalized surgical strategy. This holds especially true since pancreatic surgery is associated with a relatively high morbidity and might impair the quality of life significantly. In this article the surgical aspects in the setting of hereditary PDAC are discussed.

Acinar content at pancreatic resection margin is significantly associated with clinically relevant pancreatic fistula after partial pancreatoduodenectomy.

BACKGROUND: This study aimed to evaluate the clinical significance of acinar content at the pancreatic resection margin after partial pancreatoduodenectomy (PD). METHODS: A total of 228 consecutive patients undergoing PD were included for analysis. Resection margins were assessed for acinar, fibrosis, and fat contents by 2 pathologists blinded to the patients' clinical data. Univariate and multivariable analyses of possible predictors for clinically relevant postoperative pancreatic fistula (cr-POPF) were performed. RESULTS: The median acinar, fibrosis, and fat contents were 70% (IQR, 25%-82%), 13% (IQR, 5%-40%), and 15% (IQR, 9.25%-25%), respectively. The rates of cr-POPF were significantly higher in patients with an acinar content of >70% than in patients with an acinar content of ≤70% (26.4% vs 5.5%, respectively; P < .001). In addition, the rates of postoperative hyperamylasemia (POH) were significantly higher in patients with an acinar content of ≥70% than in patients with an acinar content of ≤70% (55.2% vs 13.8%, respectively; P < .001). The median fat content did not differ between patients with and without cr-POPF (13.0% [IQR, 7.5%-20.0%] vs 15.0% [IQR, 10.0%-30.0%], respectively; P = .06). An acinar content of >70% at the pancreatic resection margin (odds ratio [OR], 4.85; 95% CI, 1.61-14.58; P = .005) and a soft pancreatic texture (OR, 2.82; 95% CI, 1.02-7.76; P = .046) were independent predictive factors of cr-POPF in the multivariable analysis. CONCLUSION: An acinar content of ≥70% at the pancreatic resection margin was a significant predictive factor for cr-POPF after PD and was also significantly associated with POH, a precursor of cr-POPF after PD in many cases. Fatty infiltration of the pancreatic resection margin was not associated with cr-POPF.

PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms.

As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of neuroendocrine neoplasms. Therefore, our data argue toward implementation into diagnostic panels applied for NET as a firstline midgut marker.

[Personalized approach to anaplastic thyroid carcinoma]. / Personalisiertes Vorgehen beim anaplastischen Schilddrüsenkarzinom.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) represents the rarest but most aggressive tumor entity of the thyroid gland. In this respect, the treatment of advanced ATC has rapidly evolved in recent years. Recently, new personalized forms of treatment that address the somatic mutational status of the tumor have been increasingly used. The aim of this article is to provide an overview of current molecular-based and personalized treatment options for ATC. METHODS: A current literature search was performed with a focus on personalized molecular-based treatment options for ATC. RESULTS: The majority of patients suffering from ATC have an advanced tumor disease at the time of initial diagnosis. Despite multimodal treatment approaches consisting of surgery, external beam radiation therapy (EBRT) and chemotherapy (CTX), the prognosis of ATC is still poor. Accordingly, the focus of innovative treatment approaches is on molecular-based, individualized tumor therapy, including in particular BRAFV600E and multikinase inhibitors. The potential of the latter seems to lie particularly in combination therapy with immune checkpoint inhibitors. These treatment options can be used in both adjuvant and neoadjuvant settings. Neoadjuvant treatment of advanced ATC can achieve a potentially resectable treatment setting and improve the poor prognosis of affected patients; however, larger prospective and randomized studies on these combination therapies are currently pending. CONCLUSION: The focus of future treatment approaches for ATC will be on individualized, molecular-based tumor therapy. In particular, the neoadjuvant use of these therapies may change the paradigm of ATC surgery as locally advanced as well as metastatic carcinomas can be converted to a potentially resectable status and made amenable to surgery.

Serum amylase on postoperative day 1 is superior to serum lipase in predicting clinically relevant pancreatic fistula after partial pancreaticoduodenectomy.

PURPOSE: To compare the predictive value of serum amylase and lipase regarding the occurrence of clinically relevant postoperative pancreatic fistula (cr-POPF) after partial pancreaticoduodenectomy (PD). METHODS: Data from 228 consecutive patients undergoing PD were obtained from a prospective database. Serum amylase and lipase were measured on postoperative days (PODs) 0-2. Receiver-operating characteristics analysis was performed and cutoff values were tested using logistic regression. RESULTS: Serum amylase had a larger area under the curve (AUC) on POD1 (AUC 0.89, p <0.001) than serum lipase. For serum amylase POD 1, a cutoff value of 70 U/l showed sensitivity and specificity of 100% and 70% for the diagnosis of cr-POPF. Serum amylase POD 1 > 70 U/l (OR 9.815, 95% CI 3.683-26.152, p < 0.001), drain amylase POD 1 > 300 U/l (OR 2.777, 95% CI 1.071-7.197, p= 0.036), and a small (≤ 3mm) pancreatic duct diameter (OR 3.705, 95% CI 1.426-9.627, p= 0.007) were significant predictors of cr-POPF in the multivariable analysis. Patients were divided into three risk groups based on serum amylase POD 1 and pancreatic duct diameter. This model had a good performance in discriminating cr-POPF (AUC 0.846, 95% CI 0.793-0.898). The sensitivity, specificity, and negative predictive value for the combination of serum amylase POD 1 <70 U/l and pancreatic duct diameter >3 mm were 100%, 70%, and 100%. CONCLUSION: Serum amylase POD 1 was superior to serum lipase in predicting cr-POPF after PD. The proposed risk prediction model had a sensitivity and negative predictive value of 100%, allowing for early identification of cr-POPF.

Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells.

Radiotherapy and immunotherapy have shown promising efficacy for the treatment of solid malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic thyroid cancer (ATC) cells. The radiation caused a significant reduction in cell proliferation, measured by luminescence, and of the number of colonies. The addition of atezolizumab caused a further reduction in cell proliferation of the irradiated ATC cells. However, the combined treatment did not cause either the exposure of the phosphatidylserine or the necrosis, assessed by luminescence/fluorescence. Additionally, a reduction in both uncleaved and cleaved forms of caspases 8 and 3 proteins was detectable in radiated cells. The DNA damage evidenced the over-expression of TP53, CDKN1A and CDKN1B transcripts detected by RT-qPCR and the increase in the protein level of P-γH2AX and the DNA repair deputed kinases. PD-L1 protein level increased in ATC cells after radiation. Radiotherapy caused the reduction in cell viability and an increase of PD-L1-expression, but not apoptotic cell death in ATC cells. The further combination with the immunotherapeutic atezolizumab could increase the efficacy of radiotherapy in terms of reduction in cell proliferation. Further analysis of the involvement of alternative cell death mechanisms is necessary to clarify their cell demise mechanism of action. Their efficacy represents a promising therapy for patients affected by ATC.

[Outpatient parathyroid gland operations in the German system-Feasible and useful?] / Ambulante Nebenschilddrüsenoperationen im deutschen System ­ Möglich und sinnvoll?

BACKGROUND: In 2019 approximately 7500 procedures were carried out for parathyroid diseases in Germany (Statistisches Bundesamt 2020, https://www.destatis.de/DE/ ). All operations were performed as inpatient procedures. The catalogue of outpatient procedures for 2023 does not include operations on the parathyroid glands. OBJECTIVE: Which conditions are prerequisites for parathyroid surgery on an outpatient basis? MATERIAL AND METHODS: Published data on outpatient parathyroid surgery were analyzed with respect to the underlying disease, procedures performed and patient-specific circumstances. RESULTS: Initial operations for localized sporadic primary hyperparathyroidism (pHPT) seem to be suitable for outpatient surgery, provided that affected patients fulfil the general prerequisites for an outpatient operation. The procedures focused parathyroidectomy and unilateral exploration can be carried out using local or general anesthesia and have a very low risk for postoperative complications. The organization of the day of the operation and the postoperative treatment of the patient should be organized within a detailed standard of procedure. The remuneration for an outpatient parathyroidectomy is not included in the German outpatient surgery catalogue and is therefore currently not adequately financially reimbursed. CONCLUSION: In selected patients a limited initial intervention for primary hyperparathyroidism can be safely performed on an outpatient basis; however, the present German reimbursement modalities have to be revised so that the cost of these outpatient operations can be adequately covered.

Synergic Induction of Autophagic Cell Death in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma (ATC) has poor prognosis, high mortality rate and lack of effective therapy. A synergic combination of PD-L1 antibody together with cell death promoting substances like deacetylase inhibitors (DACi) and multi-kinase inhibitors (MKI) could sensitize ATC cells and promote decay by autophagic cell death. The PD-L1-inhibitor atezolizumab synergized with panobinostat (DACi) and sorafenib (MKI) leading to significant reduction of the viability, measured by real time luminescence, of three different patient-derived primary ATC cells, of C643 cells and follicular epithelial thyroid cells too. Solo administration of these compounds caused a significant over-expression of autophagy transcripts; meanwhile autophagy proteins were almost not detectable after the single administration of panobinostat, thus supporting a massive autophagy degradation process. Instead, the administration of atezolizumab caused an accumulation of autophagy proteins and the cleavage of the active caspases 8 and 3. Interestingly, only panobinostat and atezolizumab were able to exacerbate the autophagy process by increasing the synthesis, the maturation and final fusion with the lysosomes of the autophagosome vesicles. Despite ATC cells could be sensitized by atezolizumab via the cleavage of the caspases, no reduction of cell proliferation or promotion of cell death was observed. The apoptosis assay evidenced the ability of panobinostat alone and in combination with atezolizumab to induce the phosphatidil serine exposure (early apoptosis) and further the secondary necrosis. Instead, sorafenib was only able to cause necrosis. The increase of caspases activity induced by atezolizumab, the apoptosis and autophagy processes promoted by panobinostat synergize thus promoting cell death in well-established and primary anaplastic thyroid cancer cells. The combined therapy could represent a future clinical application for the treatment of such lethal and untreatable solid cancer.

Mutation-based, short-term "neoadjuvant" treatment allows resectability in stage IVB and C anaplastic thyroid cancer.

INTRODUCTION: Few available data indicate that a mutation-based "neoadjuvant" therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term "neoadjuvant" therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. METHODS: In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. PATIENTS: Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. RESULTS: In all three cases, the "neoadjuvant" therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term "neoadjuvant" treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term "neoadjuvant" therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. CONCLUSIONS: A short-term mutation-based "neoadjuvant" therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Frequency and Prognostic Significance of Intertumoural Heterogeneity in Multifocal Jejunoileal Neuroendocrine Tumours.

BACKGROUND: A recent study found that multifocal jejunoileal neuroendocrine tumors (SI-NETs) are genetically unrelated synchronous neoplasms. So far, it is unclear if this finding of synchronous independent neoplasms is mirrored by heterogeneity of key morphological parameters of SI-NETs and how it affects patient survival. METHODS: We separately assessed WHO grade (based on the Ki-67 index), expression of basal diagnostic markers (synaptophysin/chromogranin A/CDX2/serotonin), SSTR2a, and the contexture of the immunogenic microenvironment in 146 separate tumors from 28 patients with multifocal SI-NETs and correlated the results with clinicopathological factors and survival. RESULTS: Synaptophysin and chromogranin A were strongly expressed in all tumors. WHO grade was concordant within all multifocal lesions in more than 80% of cases and the highest grade was usually found in the most advanced primary. Intertumoral expression of serotonin, SSTR2, and CDX2 was discrepant in 32%, 43%, and 50% of all patients, respectively. Neither heterogeneity of any of the aforementioned markers nor multifocality itself had any impact on patient survival (p = n.s.). DISCUSSION: Multifocal SI-NET show considerable variability in some of the central diagnostic parameters. However, neither intertumoral heterogeneity of those parameters nor multifocality itself had any impact on patient survival, showing that extensive testing of all multifocal lesions is not necessarily required.

Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms.

INTRODUCTION: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). METHODS: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. RESULTS: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). CONCLUSION: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.

Indocyanine Green Near-Infrared Fluoroangiography Is a Useful Tool in Reducing the Risk of Anastomotic Leakage Following Left Colectomy.

Purpose: To evaluate whether visualization of the colon perfusion with indocyanine green near-infrared fluoroangiography (ICG-NIFA) reduces the rate of anastomotic leakage (AL) after colorectal anastomosis. Methods: Patients who underwent elective left colectomy, including all procedures involving the sigmoid colon and the rectum with a colorectal or coloanal anastomosis, were retrospectively analyzed for their demographics, operative details, and the rate of AL. Univariate and multivariate analyses were used to compare patients with and without ICG-NIFA-based evaluation. Results: Overall, our study included 132 colorectal resections [70 sigmoid resections and 62 total mesorectal excisions (TMEs)], of which 70 (53%) were performed with and 62 (47%) without ICG-NIFA. Patients' characteristics were similar between both the groups. The majority of the procedures [91 (69%)] were performed by certified colorectal surgeons, while 41 (31%) operations were supervised teaching procedures. In the ICG-NIFA group, bowel perfusion could be visualized by fluorescence (dye) in all 70 cases, and no adverse effects related to the fluorescent dye were observed. Following ICG-NIFA, the transection line was changed in 9 (12.9%) cases. Overall, 10 (7.6%) patients developed AL, 1 (1.4%) in the ICG-NIFA group and 9 (14.5%) in the no-ICG-NIFA group (p = 0.006). The multivariate analysis revealed ICG-NIFA as an independent factor to reduce AL. Conclusion: These results suggest that ICG-NIFA might be a valuable tool to reduce the rate of AL in sigmoid and rectal resections in an educational setting.

Clinical Implications of Postoperative Hyperamylasemia after Partial Pancreaticoduodenectomy.

Introduction: The present study aimed to examine the clinical implications of postoperative hyperamylasemia (POH) after partial pancreaticoduodenectomy (PD). Methods: Data from all consecutive patients undergoing PD were obtained from a prospectively maintained database and reviewed. POH was defined as an elevation of serum pancreatic amylase above the upper limit of normal (53 U/L) on postoperative days 0-2. Clinically relevant POH (cr-POH) was defined as POH in patients with clinically relevant (Clavien-Dindo ≥ III) postoperative complications. Results: POH occurred in 61 of 170 (35.9%) and cr-POH in 24 of 170 (14.1%) patients. Patients with POH had higher rates of clinically relevant postoperative pancreatic fistula (cr-POPF) (44.3 vs. 3.7%, p < 0.001) and clinically relevant postoperative complications than those without POH (39.3 vs. 21.1%, p = 0.001). Patients with cr-POH had higher C-reactive protein (CRP, milligrams per liter) levels on third (257.7 vs. 187.85 mg/L, p = 0.016) and fourth (222.5 vs. 151, p = 0.002) postoperative day (POD) than those with POH alone. Serum procalcitonin (PCT, micrograms per liter) levels on POD 2 (1.2 vs. 0.4 µg/L, p = 0.028) and POD 3 (0.85 vs. 0.4 µg/L, p = 0.001) were also higher in patients with cr-POH. Rates of cr-POPF in patients with cr-POH were higher than in those with POH alone (70.8 vs. 27%, p = 0.001). POH (OR 0.011, 95% CI: 0.001-0.097, p < 0.001) was an independent predictor of cr-POPF in the multivariable analysis. A high-risk pathology, defined as nonadenocarcinoma/nonchronic pancreatitis pathology (OR 0.277, 95% CI: 0.106-0.727, p = 0.009), and a small duct diameter (OR 0.333, 95% CI: 0.139-0.796, p = 0.013) were independent predictors of POH in the multivariable analysis. Conclusion: POH is a frequent, but not always clinically relevant, finding after partial PD. Serum CRP and PCT levels in the early postoperative period can be used to identify patients with cr-POH. POH is an independent risk factor for increased postoperative morbidity, including cr-POPF, after partial PD.

White matter integrity is disrupted in adolescents with acute anorexia nervosa: A diffusion tensor imaging study.

Anorexia nervosa (AN) is a highly debilitating mental illness with multifactorial etiology. It oftentimes begins in adolescence, therefore understanding the pathophysiology in this period is important. Few studies investigated the possible impact of the acute state of illness on white matter (WM) tissue properties in the developing adolescent brain. The present study expands our understanding of the implications of AN and starvation on WM integrity. 67 acutely ill adolescent patients suffering from AN restricting type were compared with 32 healthy controls using diffusion tensor imaging assessing fractional anisotropy (FA) and mean diffusivity (MD). We found widespread alterations in the vast majority of the WM regions with significantly decreased FA and increased MD in the AN group. In this highly selective sample in the acute stage of AN, the alterations are likely to be the consequence of starvation. Still, we cannot rule out that some of the affected regions might play a key role in AN-specific psychopathology.

Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms.

There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.