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.

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.

Heavier Weight of Resected Thyroid Specimen Is Associated With Higher Postoperative Morbidity in Benign Goiter.

OBJECTIVE: The impact of heavier weight of resected thyroid specimen on postoperative morbidity after total thyroidectomy for multinodular benign goiter remains unclear. METHODS: Data from the prospective StuDoQ|Thyroid registry of the German Society of General and Visceral Surgery were analyzed regarding the weight of the resected thyroid specimen and perioperative morbidity (vocal cord palsy, hemorrhage, surgical site infection, and hypocalcemia). To achieve a homogeneous patient population, only patients with total thyroidectomy for multinodular benign goiter were included. RESULTS: A total of 7911 patients from 105 departments underwent total thyroidectomy for benign conditions (January 2017-July 2020). The median resected weight of the thyroid specimen in all patients was 53 g (interquartile range 32-92). In 1732 patients, the specimen weight exceeded 100 g. Intraoperative neuromonitoring was used in 99.5% of patients. Postoperative laryngoscopy revealed vocal cord dysfunction in 480 of 15 822 (3.03%) nerves at risk, with unilateral dysfunction in 454 (2.87%) of patients and bilateral dysfunction in 13 patients (0.08%). In multivariable analysis, a thyroid weight >100 g was an independent predictor of early postoperative vocal cord dysfunction [odds ratio (OR) 1.462, 95% CI 1.108-1.930, P = 0.007). Heavier (>100 g) thyroid weight was an independent predictor of surgical site infection (OR 1.861, 95% CI 1.203-2.880, P = 0.005) and also predicted postoperative hemorrhage in the univariate analysis (OR 1.723, 95% CI 1.027-2.889, P = 0.039). On the contrary, postoperative parathyroid function was not affected. CONCLUSIONS: Heavier (>100 g) resected thyroid weight independently predicts higher postoperative morbidity, including early vocal cord palsy and surgical site infection after total thyroidectomy for benign multinodular goiter.

Pancreatic Apoplexy: Fulminant Necrotizing Pancreatitis Leading to Completion Pancreatectomy Within 3 Days After Partial Pancreaticoduodenectomy.

OBJECTIVES: Patient characteristics with postoperative acute necrotizing pancreatitis and completion pancreatectomy (CP) after pancreaticoduodenectomy (PD) remain unclear. METHODS: Data from all patients who underwent a PD with need for CP (January 2011-December 2019) at a German University Hospital were analyzed regarding the indications and timing of CP, laboratory and histopathological findings, and overall outcome. RESULTS: Six hundred twelve patients underwent PD, 33 (5.4%) of them needed a CP. Indications were grade C pancreatic fistula with or without biliary leak (46% and 12%), biliary leak (6%), and hemorrhage due to pancreatic fistula (36%). Eight patients (24%) underwent CP within 3 days after PD. These fulminant courses ("pancreatic apoplexy") were accompanied by significantly higher levels of lactate dehydrogenase, C-reactive protein, serum amylase, serum lipase, drain amylase, and drain lipase compared with patients with CP after the third day. Pancreatic apoplexy was histologically associated with higher rates of pancreatic necrosis (P = 0.044) and hemorrhage (P = 0.001). A trend toward higher mortality was observed (75% vs 36%, P = 0.058). CONCLUSIONS: Pancreatic apoplexy, defined as fulminant necrotizing pancreatitis after PD leading to CP within 3 days, is associated with characteristic laboratory and histopathological findings and a trend to higher mortality.

Long Non-Coding RNA H19 Expression Correlates with Autophagy Process in Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is characterized by poor prognosis and high mortality. The suppression of the long-non-coding RNA H19, counterbalanced by IGF2 over-expression, leads to down-regulation of the autophagy markers, high proliferation rate and metastatic potential in patients affected by ACC. The administration of the deacetylase inhibitors (DACi) panobinostat, trichostatin A (TSA) and SAHA affected the cell viability of H295R monolayer and spheroids and induced the over-expression of H19 and autophagy transcripts. H19 knock down in H295R cells was not able to modulate the expression level of autophagy transcripts. Instead, H19 knock down was able to impede the ability of DACi to modulate the protein level of the autophagy markers. Furthermore, the administration of higher concentration of DACi was able to down-regulate the protein level of Beclin1 and p62 and to induce the conversion of LC3B-I into the active LC3B-II form, thus confirming an active autophagic process. Neither the active protein level nor the activity of caspases 8 and 3 was prompted by the DACi, thus excluding the involvement of the executioners of apoptosis in H295R decay. The DACi restore H19, the autophagy markers and trigger cell death in ACC cells. The re-activation of autophagy would represent a novel strategy for the treatment of patients affected by this severe malignancy.

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.

Temporal encephaloceles in epilepsy patients and asymptomatic cases: Size may indicate epileptogenicity.

OBJECTIVE: This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE), as well as in asymptomatic cases. METHODS: Four hundred fifty-eight magnetic resonance imaging scans were examined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs). RESULTS: At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval [CI] = 5.3%-15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%-7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%-5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC subjects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723-1.00, p = .001). SIGNIFICANCE: Temporal encephaloceles may occur without presenting any clinical symptoms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity.

Postoperative morbidity following pancreatic cancer surgery is significantly associated with worse overall patient survival; systematic review and meta-analysis.

BACKROUND: The influence of postoperative morbidity on survival after potentially curative resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: Medline, Web of Science and Cochrane Library were searched for studies reporting survival in patients with and without complications, defined according to the Clavien-Dindo classification, after primary, potentially curative resection for pancreatic cancer followed by adjuvant treatment. Meta-analysis was performed using a random-effects model. RESULTS: Fourteen retrospective cohort studies comprising a total of 7.604 patients with an overall complication rate of 40.8% (n = 3.103 patients) were included. Median overall survival for the entire patient cohort ranged from 15.5 to 24 months. Overall survival in patients with severe postoperative complications ranged from 7.1 to 37.1 months and was significantly worse compared to the overall survival in patients without severe complications ranging from 16.5 to 38.2 months. Postoperative complication rates ranged from 24.3% to 64%, severe (Clavien-Dindo ≥ III) complication rates from 4.2% to 31%. Results sufficient for meta-analysis were reported by ten studies, representing 6.028 patients. Meta-analysis showed reduced overall survival following any complication (summary adjusted HR 1.47; 95% CI 1.23-1.76, p < 0.0001). Hazard of death was 1.5 times higher in patients experiencing severe postoperative complications than in patients without severe complications (summary adjusted HR 1.45; 95% CI 1.13-1.85, p = 0.003). CONCLUSIONS: Postoperative complications after potentially curative resection of PDAC are significantly associated with worse overall patient survival.

The German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa)­Knowledge Gained in 20 Years.

BACKGROUND: Familial pancreatic carcinoma (FPC) is a rare hereditary tumor syndrome with a heterogeneous clinical phenotype. The study of FPC also contributes to a better understanding of the more common sporadic pancreatic ductal adenocarcinoma (PDAC). We report on the past 20 years' experience of the German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa) of the German Cancer Aid (Deutsche Krebshilfe). METHODS: From 1999 onward, families in which at least two first-degree relatives had PDAC, and which did not meet the criteria for any other tumor syndrome, have been entered into the FaPaCa registry and analyzed both clinically and with molecular genetic techniques. Persons at risk are offered the opportunity to participate in an early detection program. RESULTS: From June 1999 to June 2019, 227 families (a total of 2579 persons) met the criteria for entry into the FaPaCa registry. PDAC was the sole tumor entity present in 37% of the families (95% confidence interval [31.1; 44.1]); in the remaining 63% [55.9; 68.9], other tumor types were present as well, particularly breast cancer (70 families, 31% [24.9; 37.3]), colon carcinoma (25 families, 11% [7.3; 15.8]) , and melanoma (22 families, 9.7% [6.2; 14.3]). The mode of inheritance of PDAC was autosomal dominant in 72% [65.5; 77.6] of the families. Predisposing germ-line mutations were found in 25 of the 150 (16.7%) families studied, in the following genes: BRCA2 (9 families), CDKN2A (5 families), PALB2 (4 families), BRCA1 (3 families), ATM (2 families), and CHEK2 (2 families). The early detection program revealed high-grade cancer precursor lesions or a PDAC in 5 of the participating 110 persons at risk (4.5%, [1.5; 10.3] during a period of observation of at least five years. CONCLUSION: The care of families with FPC is complex and should be provided in centers with the necessary expertise. Prospective, controlled longitudinal studies are needed to determine whether the screening of persons at risk for PDAC truly lessens mortality and is cost-effective.

Gastric enterochromaffin-like cell changes in multiple endocrine neoplasia type 1.

BACKGROUND: Gastric enterochromaffin-like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES. METHODS: Multiple endocrine neoplasia type 1 patients being part of a regular screening program (2014-2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin- and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed. RESULTS: Thirty-eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p < .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464). CONCLUSION: Enterochromaffin-like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.

Adult Proinsulinomatosis Associated With a MAFA Germline Mutation as a Rare Cause of Recurrent Hypoglycemia.

ABSTRACT: Sporadic adult insulinomatosis is an extremely rare clinical condition. Adult proinsulinomatosis has not yet been described. We report the case of a 48-year-old female patient with recurrent hypoglycemia caused by benign proinsulin-secreting pancreatic neuroendocrine neoplasias (pNENs) with no history of multiple endocrine neoplasia type 1. Initial workup revealed elevated serum proinsulin levels and a positive fasting test. Magnetic resonance imaging and endosonography visualized 2 pNENs in the pancreatic body and tail that were treated by robotic-assisted enucleation. After initial biochemical cure, the patient's hypoglycemia recurred 3 months after surgery. Imaging showed a new lesion in the pancreatic body, so that now a spleen-preserving subtotal distal pancreatectomy was performed. The pathological examination revealed 17 neuroendocrine microadenomas and 1 well-differentiated pNEN (Ki-67% 1%-2%) of 22-mm size as well as more than 200 (pro)insulin-producing ß-cell precursor lesions, confirming the diagnosis of adult proinsulinomatosis. Mutation analysis of the germline DNA identified the in-frame deletion mutation (p.His207del) in the MAFA gene on chromosome 8. The patient was biochemically cured 16 months after the last surgical resection. Similarly to adult insulinomatosis, the presence of proinsulin-secreting tumors causes recurrent hypoglycemia and might be associated with germline mutations in the MAFA gene.

Modulation of Pancreatic Neuroendocrine Neoplastic Cell Fate by Autophagy-Mediated Death.

INTRODUCTION: Autophagic cell death in cancer cells can be mediated by inhibition of deacetylases. Although extensive studies have focused on the autophagic process in cancer, little is known about the role of autophagy in degrading cytosolic and nuclear components of pancreatic neuroendocrine neoplastic (pNEN) cells leading to cell death, thus improving the therapy of patients affected by pNEN. METHODS: 2D and 3D human pNEN and pancreatic stellate cells were treated with panobinostat and bafilomycin. Autophagy markers were detected by RT-qPCR, immunofluorescence, and Western blot. Autophagosomes were detected by electron microscopy and their maturation by real-time fluorescence of LC3B stable transfected cells. ChIP was performed at the cAMP responsive element. Immunofluorescence was performed in murine pancreatic tissue. RESULTS: We observed that pan-deacetylase inhibitor panobinostat treatment causes autophagic cell death in pNEN cells. We also found that although AMPK-α phosphorylation is counterbalanced by phosphorylated AKT, it is not capable to inhibiting autophagic cell death. However, the binding activity of the cAMP responsive element is prompted by panobinostat. Although autophagy inhibition prevented autophagosome synthesis, maturation, and cell death, panobinostat treatment induced the accumulation of mature autophagosomes in the cytosol and the nucleus, leading to disruption of the organelles, cellular digestion, and decay. Observation of autophagosome membrane proteins Beclin1 and LC3B aggregation in murine pancreatic islets indicates that autophagy restoration may also lead to autophagosome aggregation in murine insulinoma cells. A basal low expression of autophagy markers was detectable in patients affected by pNEN, and, interestingly, the expression of these markers was significantly lower in metastatic pNEN. DISCUSSION/CONCLUSION: Our study highlights that the autophagy functional restoration and prolongation of this catabolic process, mediated by inhibition of deacetylase, is responsible for the reduction of pNEN cells. Prompting of autophagy cell death could be a promising strategy for the therapy of pNEN.

Preoperative Bacterobilia Is an Independent Risk Factor of SSIs after Partial PD.

INTRODUCTION: The impact of bacterobilia on postoperative surgical and infectious complications after partial pancreaticoduodenectomy (PD) is still a matter of debate. METHODS: All patients undergoing PD with and without a preoperative biliary drainage (PBD) with complete information regarding microbial bile colonization were included. Logistic regression was applied to assess the influence of bacterobilia on postoperative outcome. RESULTS: One hundred seventy patients were retrospectively analysed. Clinically relevant postoperative complications (Clavien-Dindo ≥ III) occurred in 40 (23.5%) patients, clinically relevant postoperative pancreatic fistulas in 29 (17.1%) patients, and surgical site infections (SSIs) in 16 (9.4%) patients. Thirty-seven of 39 (94.9%) patients with PBD and 33 of 131 (25.2%) patients without PBD had positive bile cultures (p < 0.001). A polymicrobial bile colonization was reported in 9 of 33 (27.3%) patients without PBD and 27 of 37 (73%) patients with PBD (p < 0.001). Resistance to ampicillin-sulbactam was shown in 26 of 37 (70.3%) patients with PBD and 12 of 33 (36.4%) patients without PBD (p = 0.001). PBD (OR 0.015, 95% CI 0.003-0.07, p < 0.001) and male sex (OR 3.286, 95% CI 1.441-7.492, p = 0.005) were independent predictors of bacterobilia in the multivariable analysis. Bacterobilia was the only independent predictor of SSIs in the multivariable analysis (OR 0.143, 95% CI 0.038-0.535, p = 0.004). CONCLUSIONS: Patients with a PBD show significantly higher rates of bacterobilia, polymicrobial bile colonization, and resistance to ampicillin-sulbactam. Bacterobilia is an independent predictor of SSI after PD.

C-reactive protein and drain amylase accurately predict clinically relevant pancreatic fistula after partial pancreaticoduodenectomy.

BACKROUND: C-reactive protein (CRP) and procalcitonin (PCT) have shown to be reliable predictors of inflammatory complications and anastomotic leak after colorectal surgery. Their predictive value after partial pancreaticoduodenectomy (PD) remains unclear. MATERIALS AND METHODS: All consecutive pancreaticoduodenectomies (2009-2018) at our hospital were included. Drain amylase was evaluated on postoperative day (POD) 1, serum CRP and PCT were evaluated on POD 1-3. Receiver-operating characteristics curves were performed and significant cut-off values were tested using logistic regression. RESULTS: Among 188 patients who underwent partial PD, clinically relevant pancreatic fistulas (POPF) occurred in 30 (16%) patients, including 20 (10.6%) with Grade B and 10 (5.3%) patients with Grade C. Postoperative complications (Clavien-Dindo ≥ III) were reported in 46 (24.5%) patients, including Grade IIIa in 16 (8.5%), IIIb in 18 (9.6%), IVa in 3 (1.6%), IVb in 2 (1.1%) and V in 7 (3.7%) patients. Drain amylase on POD 1 showed the largest area under the curve (0.872, p < 0.001), followed by CRP (0.803, p < 0.001) and PCT on POD 3 (0.651, p < 0.011). Drain amylase on POD 1 > 303 U/l (OR 0.045, 95% CI 0.010-0.195, p < 0.001), CRP > 203 mg/l (OR 0.098, 95% CI 0.041-0.235, p < 0.001) and PCT > 0.85 µg/l (OR 0.393, 95%CI 0.178-0.869, p = 0.02) were significant predictors of relevant POPF in the univariate analysis. CRP > 203 mg/l (OR 0.098, 95% CI 0.024-0.403, p = 0.001) and drain amylase > 303 U/l (OR 0.064, 95% CI 0.007-0.554, p = 0.01) remained independent predictors in the multivariable analysis. The combination of drain amylase on POD 1 and CRP on POD 3 had a sensitivity and specificity of 87.4% and 90.9% to predict relevant POPF. CONCLUSION: Drain amylase on POD 1 and CRP on POD 3 can accurately predict clinically relevant POPF after partial pancreaticoduodenectomy. The accuracy of PCT on POD 3 is limited.

Single gland excision for MEN1-associated primary hyperparathyroidism.

IMPORTANCE: Guidelines advocate subtotal parathyroidectomy (SPTX) or total parathyroidectomy with autotransplantation (TPTX) with bilateral cervical thymectomy for primary hyperparathyroidism (pHPT) associated with multiple endocrine neoplasia type 1 (MEN1). However, both procedures are associated with a significant risk of permanent hypoparathyroidism. OBJECTIVE: The aim of the current study was to compare long-term results of either single gland excision (SGE, 1-2 glands), SPTX and TPTX for the treatment of MEN1-associated pHPT. DESIGN AND SETTING: Data of genetically confirmed MEN1 patients who underwent surgery for pHPT between 1987 and 2017 were retrieved from a prospective database and were retrospectively analysed. RESULTS: Eighty-nine MEN1 patients underwent either TPTX (n = 38, 42.7%), SPTX (n = 23, 25.8%) or SGE (n = 28, 31.5%). The rate of disease persistence after initial surgery was 2.6%, 0% and 14.2% in the TPTX, SPTX and SGE groups, respectively. After median follow-up of 112 (range 7-411) months, the rate of recurrent pHPT was significantly higher in the SGE group (n = 19, 21.3%) compared with the TPTX (n = 4, 4.4%, P = .001) and the SPTX (n = 9, 10.1%, P = .03) groups. Analysis of the recurrence-free time among the surgical groups revealed a significant difference (P = .036). The median time to recurrence was significantly shorter after SGE (101, range 3-301 months) than after SPTX (139, range 28-278 months, P = .018) and TPTX (204, range 75-396 months, P = .049). Twelve (32%) patients who underwent TPTX developed permanent hypoparathyroidism compared with only 4 (17%, P = .06) in the SPTX and 0 in the SGE group (P = .001). CONCLUSION: Given the high rate of postoperative permanent hypoparathyroidism after TPTX and SPTX, SGE is a valid option for the treatment of MEN1-associated pHPT.

Palliative surgical bypass is superior to palliative endoscopic stenting in patients with malignant gastric outlet obstruction: systematic review and meta-analysis.

BACKGROUND: Gastrojejunostomy (GJ) and self-expanding metal stents (SEMS) are the two most common palliative treatment options for patients with malignant gastric outlet obstruction (GOO). Randomised trials and retrospective studies have shown discrepant results, so that there is still a controversy regarding the optimal treatment of GOO. METHODS: Medline, Web of Science and Cochrane Library were systematically searched for studies comparing GJ to SEMS in patients with malignant GOO. Primary outcomes were survival and postoperative mortality. Secondary outcomes were frequency of re-interventions, major complications, time to oral intake and length of hospital stay. RESULTS: Twenty-seven studies, with a total of 2.354 patients, 1.306 (55.5%) patients in the SEMS and 1.048 (44.5%) patients in the GJ group, were considered suitable for inclusion. GJ was associated with significantly longer survival than SEMS (mean difference 43 days, CI 12.00, 73.70, p = 0.006). Postoperative mortality (OR 0.55, CI 0.27, 1.16, p = 0.12) and major complications (OR 0.73, CI 0.5, 1.06, p = 0.10) were similar in both groups. The frequency of re-interventions, however, was almost three times higher in the SEMS group (OR 2.95, CI: 1.70, 5.14, p < 0.001), whereas the mean time to oral intake and length of hospital stay were shorter in the SEMS group (mean differences - 5 days, CI - 6.75, - 3.05 days, p < 0.001 and - 10 days, CI - 11.6, - 7.9 days, p < 0.001, respectively). CONCLUSIONS: Patients with malignant GOO and acceptable performance status should be primarily considered for a palliative GJ rather than SEMS.

Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry.

PURPOSE: Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. METHODS: Patients who underwent surgery for pNENs (April 2013-June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. RESULTS: A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016-0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. CONCLUSION: In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.

Incidental findings in pancreas screening programs for high-risk individuals: Results from three European expert centers.

Background: Widespread abdominal imaging has led to a substantial increase in the detection of incidentalomas. Currently, an increasing number of centers offer surveillance of the pancreas to individuals at high risk (IARs) of pancreatic ductal adenocarcinoma (PDAC). Objective: The aims of this study were to evaluate the frequency and type of incidental findings in a magnetic resonance imaging (MRI)-based surveillance program for IARs for PDAC, and to discuss the benefit of detecting these lesions. Methods: The outcome of MRI screening was reviewed in 568 individuals from three long-term pancreas surveillance programs conducted at three large European expert centers. All MRIs were studied in detail for the presence of incidental lesions. Results: The most common lesions were liver cysts, renal cysts and liver hemangioma, which together comprised 75% of all lesions. Only five (0.9%) patients underwent surgery for a benign lesion. Cancer was detected in 11 patients (1.9%); early detection of tumors was beneficial in at least five cases. Conclusion: The present study demonstrates that extrapancreatic incidentaloma is a common finding in IARs for PDAC, but rarely requires additional treatment. CDKN2A-p16-Leiden mutation carriers were the only patient group found to harbor a substantial number of cancers, and detection resulted in benefit in several cases.