Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens.

BACKGROUND: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing. METHODS: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation. RESULTS: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations. CONCLUSION: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing.

SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.

AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection. METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected. DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy. TRIAL REGISTRATION: NCT05010850.

Discordance in Total Mesorectal Excision Specimen Grading in a Prospective Phase 2 Multicenter Rectal Cancer Trial: Are We Overestimating the Quality of Our Resections?

OBJECTIVES: To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase 2 trial of transanal TME. BACKGROUND: Grading of TME specimens is based on the macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described. METHODS: A phase 2 prospective transanal TME trial was conducted from 2017 to 2022 across 11 North American centers with TME quality as the primary study endpoint. QC measures included (1) training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance before trial reporting. Cohen Kappa statistic was used to assess agreement in grading. RESULTS: Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ = 0.35; 95% CI: 0.10-0.61; P < 0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases, respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre versus postreconciliation rates of complete or NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC-NC; N = 1) or major downgrade (NC/C-IC, N = 4) in 5 cases overall (5%). CONCLUSIONS: A 14% rate of major discordance was observed in TME grading between the site and central reviewers. The resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through a central review of TME photographs and reconciliation of major discordances is strongly recommended.

Robust methylation-based classification of brain tumours using nanopore sequencing.

BACKGROUND: DNA methylation-based classification of cancer provides a comprehensive molecular approach to diagnose tumours. In fact, DNA methylation profiling of human brain tumours already profoundly impacts clinical neuro-oncology. However, current implementation using hybridisation microarrays is time consuming and costly. We recently reported on shallow nanopore whole-genome sequencing for rapid and cost-effective generation of genome-wide 5-methylcytosine profiles as input to supervised classification. Here, we demonstrate that this approach allows us to discriminate a wide spectrum of primary brain tumours. RESULTS: Using public reference data of 82 distinct tumour entities, we performed nanopore genome sequencing on 382 tissue samples covering 46 brain tumour (sub)types. Using bootstrap sampling in a cohort of 55 cases, we found that a minimum set of 1000 random CpG features is sufficient for high-confidence classification by ad hoc random forests. We implemented score recalibration as a confidence measure for interpretation in a clinical context and empirically determined a platform-specific threshold in a randomly sampled discovery cohort (N = 185). Applying this cut-off to an independent validation series (n = 184) yielded 148 classifiable cases (sensitivity 80.4%) and demonstrated 100% specificity. Cross-lab validation demonstrated robustness with concordant results across four laboratories in 10/11 (90.9%) cases. In a prospective benchmarking (N = 15), the median time to results was 21.1 h. CONCLUSIONS: In conclusion, nanopore sequencing allows robust and rapid methylation-based classification across the full spectrum of brain tumours. Platform-specific confidence scores facilitate clinical implementation for which prospective evaluation is warranted and ongoing.

Monitoring of C-reactive protein decreases length of stay after laparoscopic total mesorectal excision for cancer: a prospective case-matched study in 236 patients.

AIM: The aim of this study was to evaluate a discharge strategy driven by monitoring of C-reactive protein (CRP) in a homogeneous group of patients undergoing laparoscopic total mesorectal excision with sphincter-saving surgery for rectal cancer (TME). METHOD: One hundred and thirteen patients who underwent a TME had CRP monitoring on postoperative day (POD) 5. Patients were discharged on POD 6 if the CRP level was ≤100 mg/L. Patients were matched (according to age, gender, body mass index, neoadjuvant pelvic irradiation and type of anastomosis) to 123 control patients who underwent the same operation with the same postoperative care but without CRP monitoring. RESULTS: Postoperative 3-month overall [CRP group 62/113 (55%) vs controls 73/123 (59%); p = 0.487] and severe (i.e. Clavien-Dindo grade 3 and above) [CRP group 17/113 (15%) vs controls 19/123 (15%); p = 0.931] morbidity rates were similar between groups. Mean length of hospital stay (LHS) was significantly shorter in the CRP group (CRP group 9.7 ± 14 days vs controls 11.6 ± 7 days; p < 0.001). Discharge occurred on POD 6 in 55/113 (49%) patients from the CRP group vs 7/123 (6%) from the control group (p < 0.001). The rehospitalization rate [CRP group 19/113 (17%) vs controls 13/123 (11%); p = 0.177] was similar between groups. The CRP level on POD 5 had a diagnostic property to assess an anastomotic leakage with an area under the curve of 0.81. CONCLUSION: In patients who underwent TME, a discharge strategy based on CRP monitoring significantly decreased LHS without increasing morbidity, mortality or rehospitalization rates.

Indomethacin promotes survival of new neurons in the adult murine hippocampus accompanied by anti-inflammatory effects following MPTP-induced dopamine depletion.

BACKGROUND: Parkinson's disease (PD) is characterized by dopaminergic cell loss and inflammation in the substantia nigra (SN) leading to motor deficits but also to hippocampus-associated non-motor symptoms such as spatial learning and memory deficits. The cognitive decline is correlated with impaired adult hippocampal neurogenesis resulting from dopamine deficit and inflammation, represented in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model of PD. In the inflammatory tissue, cyclooxygenase (COX) is upregulated leading to an ongoing inflammatory process such as prostaglandin-mediated increased cytokine levels. Therefore, inhibition of COX by indomethacin may prevent the inflammatory response and the impairment of adult hippocampal neurogenesis. METHODS: Wildtype C57Bl/6 and transgenic Nestin-GFP mice were treated with MPTP followed by short-term or long-term indomethacin treatment. Then, aspects of inflammation and neurogenesis were evaluated by cell counts using immunofluorescence and immunohistochemical stainings in the SN and dentate gyrus (DG). Furthermore, hippocampal mRNA expression of neurogenesis-related genes of the Notch, Wnt, and sonic hedgehog signaling pathways and neurogenic factors were assessed, and protein levels of serum cytokines were measured. RESULTS: Indomethacin restored the reduction of the survival rate of new mature neurons and reduced the amount of amoeboid CD68+ cells in the DG after MPTP treatment. Indomethacin downregulated genes of the Wnt and Notch signaling pathways and increased neuroD6 expression. In the SN, indomethacin reduced the pro-inflammatory cellular response without reversing dopaminergic cell loss. CONCLUSION: Indomethacin has a pro-neurogenic and thereby restorative effect and an anti-inflammatory effect on the cellular level in the DG following MPTP treatment. Therefore, COX inhibitors such as indomethacin may represent a therapeutic option to restore adult neurogenesis in PD.

Anastomotic leakage after side-to-end anastomosis for rectal cancer: does leakage location matter?

AIM: To assess outcome according to location of anastomotic leakage (AL) after side-to-end stapler or manual low colorectal or coloanal anastomosis following laparoscopic total mesorectal excision (TME) for rectal cancer. METHODS: All patients presenting with symptomatic or asymptomatic AL after TME and side-to-end low anastomosis for rectal cancer performed from 2005 to 2014 were identified from our prospective database. CT-scans with contrast enema were reviewed to assess location of AL origin. RESULTS: Among 279 patients who underwent TME with side-to-end anastomosis from 2005 to 2014, 70 patients presented with AL and were included: 43 (61%) patients with AL on the circular anastomosis (CAL) were compared to 27 (39%) with AL on the transverse stapling line of the colonic stump (TAL). CAL and TAL were associated with similar rates of symptomatic AL (63% versus 48%, respectively; p=0.339), severe postoperative morbidity rate (33% versus 18%; p=0.313), and long-term outcomes, including definitive stoma rate (10 versus 11%; p=0.622), and major low anterior resection syndrome rate (56% vs 57%; p=0.961). CONCLUSION: Our study showed that whatever the location of AL on a side-to-end low colorectal or coloanal anastomosis after TME for cancer, both short and long-term outcomes are similar. This article is protected by copyright. All rights reserved.

Risk factors for prolonged postoperative ileus after laparoscopic sphincter-saving total mesorectal excision for rectal cancer: an analysis of 428 consecutive patients.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a common complication after colorectal resection but data regarding PPOI risk factors after laparoscopic rectal cancer surgery is lacking. This study aimed to identify risk factors for PPOI after laparoscopic sphincter-saving total mesorectal excision (TME) for cancer. METHODS: All patients who underwent a laparoscopic sphincter-saving TME for cancer from 2005 to 2014 were identified from our prospective database. PPOI was defined as abdominal distension, nausea, and/or vomiting, requiring a nasogastric tube insertion, during the postoperative period. RESULTS: Among 428 consecutive patients, 65 patients (15%) presented with POI. In multivariate analysis, male gender (Odds Ratio (OR) 2.3 [1.1-4.5]; p = 0.026, age >70 years (OR: 2.0 [1.1-4.0]; p = 0.037)], conversion to open approach (OR 4.9 [1.5-15.4]; p = 0.007), and intra-abdominal surgical site infection (OR 3.8 [1.9-7.5]; p < 0.001) were identified as independent risk factor for PPOI. PPOI risk was 5% in patients without any risk factor but raised to 11, 28, and 54% in patients with 1, 2, or ≥3 risk factors, respectively (p < 0.001). CONCLUSION: PPOI is observed in 15% of the patients after laparoscopic sphincter-saving surgery for rectal cancer. We identified four independent factors for PPOI in multivariate analysis: male, gender, age >70, conversion to open approach, and intra-abdominal surgical site infection, leading to the construction of a simple and pragmatic predictive score. This score might help the surgeon to assess patient at risk of PPOI.

Is the benefit of laparoscopy maintained in elderly patients undergoing rectal cancer resection? An analysis of 446 consecutive patients.

BACKGROUND: Several studies showed that age is significantly associated with impaired outcomes after open colorectal surgery. However, very few data exist on laparoscopic rectal cancer surgery in elderly patients. The aim of this study was to assess operative results of laparoscopic rectal cancer surgery according to age. METHODS: From 2005 to 2014, 446 consecutive patients who underwent laparoscopic rectal cancer resection were identified from a prospective database. Five groups were defined: age <45 (n = 44), 45-54 (n = 80), 55-64 (n = 166), 65-74 (n = 95) and ≥75 years (n = 61). RESULTS: Elderly patients presented significantly higher ASA score (p = 0.004), higher Charlson comorbidity index (p < 0.0001) and more frequent cardiovascular, pulmonary (p < 0.0001) and neurological (p = 0.03) comorbidities. Overall postoperative morbidity rate was similar between groups (34-35-37-43-43 %, p = 0.70). Medical morbidity slightly increased with age (14-9-14-19-26 %, p = 0.06), but there was no significant difference regarding clinical anastomotic leakage, surgical morbidity, major morbidity (Dindo ≥3), cardiopulmonary complications and length of hospital stay. In multivariate analysis, age was not an independent factor for postoperative morbidity, unlike ASA score ≥3 (p = 0.039), neoadjuvant radiotherapy/chemoradiotherapy (p = 0.034) and operative time ≥240 min (p = 0.013). CONCLUSIONS: This study showed that laparoscopic rectal cancer resection might safely be performed irrespective of age.

Persistent Asymptomatic Anastomotic Leakage After Laparoscopic Sphincter-Saving Surgery for Rectal Cancer: Can Diverting Stoma Be Reversed Safely at 6 Months?

BACKGROUND: Anastomotic leakage after rectal cancer surgery raises the problem of the timing of diverting stoma reversal. OBJECTIVE: The purpose of this study was to assess whether stoma reversal can be safely performed at 6 months after laparoscopic sphincter-saving surgery for rectal cancer with total mesorectal excision in patients with persistent asymptomatic anastomotic leakage. DESIGN: This was a retrospective analysis of a prospective database. SETTINGS: The study was conducted at a tertiary colorectal surgery referral center. PATIENTS: All of the patients with anastomotic leakage were treated conservatively after sphincter-saving laparoscopic total mesorectal excision for rectal cancer. MAIN OUTCOME MEASURES: The main study measure was postoperative morbidity. RESULTS: A total of 110 (26%) of 429 patients who presented with anastomotic leakage and were treated conservatively were diagnosed only on CT scan (60 symptomatic (14%) and 50 asymptomatic (12%)). During follow up, 82 (75%) of 110 anastomotic leakages healed spontaneously after a mean delay of 16 ± 6 weeks (range, 4-30 weeks). Among these patients, 7 (9%) of 82 developed postoperative symptomatic pelvic sepsis after stoma reversal. Among the 28 patients remaining, 3 died during follow-up. The remaining 25 patients (23%) presented with persistent asymptomatic anastomotic leakage with chronic sinus >6 months after rectal surgery. Stoma reversal was performed in 19 asymptomatic patients, but 3 (16%) of 19 developed postoperative symptomatic pelvic sepsis after stoma reversal (3/19 vs 7/82 patients; p = 0.217), requiring a redo surgery with transanal colonic pull-through and delayed coloanal anastomosis (n = 2) or standard coloanal anastomosis (n = 1). Regarding the 6 final patients, abdominal redo surgery was performed because of either symptoms or anastomotic leakage with a large presacral cavity. LIMITATIONS: This study was limited by its small sample size. CONCLUSIONS: In the great majority of patients with persistent anastomotic leakage at 6 months after total mesorectal excision, stoma reversal can be safely performed.

Laparoscopic extended right colectomy versus laparoscopic left colectomy for carcinoma of the splenic flexure: a matched case-control study.

PURPOSE: The aim of the study was to compare the short- and long-term outcomes of laparoscopic extended right colectomy (ER) versus laparoscopic left colectomy (LC) for splenic flexure carcinomas. METHODS: Patients with stage 0-III adenocarcinoma of the splenic flexure who underwent laparoscopy between 2000 and 2013 were identified from a prospectively maintained database. Twenty-seven patients who underwent ER were matched by age, gender, BMI, ASA score, and tumor stage with 27 patients who underwent LC. RESULTS: The ER procedures were significantly longer than LC (235 ± 49.2 min vs. 192 ± 43.4 min, p = 0.001, respectively). Post-operatively, time to flatus and return to regular diet were observed to average 2.4 ± 0.8 days (1-4 days) and 4.6 ± 1.05 days (3-8 days), respectively, without differences between the groups. Overall, 14 complications were observed in 12 patients and 90-day mortality was nil. The length of hospitality stay was not different between ER and LC, with an overall mean of 8.3 ± 2.7 days. All procedures were classified as R0 resections, but ER was associated with a higher number of lymph nodes retrieved (21.4 ± 4.9) compared with LC (16.6 ± 5.5, p = 0.001). The 1-, 3-, and 5-year cumulative survival rates were 92.6, 85.8, and 72.8% for the ER group and 96.3, 91.9, and 75.1% for the LC group (p = 0.851). The 1-, 3-, and 5-year disease-free survival rates were 85.2, 76.7, and 67.1% for the ER group and 96.2, 75.5, and 66.7% for the LC group (p = 0.636). CONCLUSIONS: Laparoscopic ER and LC procedures performed for splenic flexure carcinomas appear to have similar short- and long-term oncologic outcomes.

Adult intracranial ependymoma-relevance of DNA methylation profiling for diagnosis, prognosis, and treatment.

BACKGROUND: A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. METHODS: Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS). RESULTS: The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes. CONCLUSIONS: DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.

Perioperative outcomes of pheochromocytoma/paraganglioma surgery preceded by Takotsubo-like cardiomyopathy.

BACKGROUND: Pheochromocytomas and paragangliomas can induce severe cardiovascular manifestations such as Takotsubo-like cardiomyopathy. What the perioperative outcomes are of patients presenting with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy remains an unresolved question. METHODS: From 2006 to 2019, all patients who underwent surgery for pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy were included from 3 high-volume centers, with specific attention to perioperative hemodynamic instability and postoperative outcomes. RESULTS: Overall, 37 patients were included, with a median age of 45 years. Patients were operated on 2 months (1-4) after a Takotsubo-like cardiomyopathy episode; 33 (89%) had a laparoscopic approach. All those who underwent surgery presented in a hemodynamically stable situation. All except 1 of the pheochromocytomas/paragangliomas patients had at least 1 antihypertensive treatment at the time of surgery. The median preoperative systolic blood pressure in the Takotsubo-like cardiomyopathy group was 120 mm Hg (95-132). Overall, 27/34 (79%) of patients required vasoactive drugs during surgery with nicardipine (n = 22), esmolol (n = 12), and/or norepinephrine (n = 8). No patient presented a catecholamine-induced life-threatening complication such as hypertensive crisis, cardiac arrhythmias, pulmonary edema, cardiac ischemia, or Takotsubo-like cardiomyopathy in the perioperative period. Severe morbi-mortality was nil. The systematic review identified 5 studies including 38 pheochromocytomas/paragangliomas patients with at least 1 episode of acute heart failure considered as Takotsubo-like cardiomyopathy before surgery, of which 28 patients had delayed surgery with 1 postoperative death. CONCLUSION: Hemodynamically stabilized patients with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy can be safely scheduled for an elective pheochromocytomas/paragangliomas surgery, with similar intra and postoperative outcomes as those without Takotsubo-like cardiomyopathy.

Preoperative assessment of patient comorbidities before left colectomy: Comparison between ASA performance status scale and a new computed tomography physical status score.

PURPOSE: To compare a newly developed preoperative computed tomography physical status (CT-PS) score with the American Society of Anesthesiology performance status (ASA-PS) scale in the assessment of patient preoperative health status and stratification of perioperative risk before left colectomy. MATERIALS AND METHODS: Preoperative chest-abdomen-pelvis CT examinations of patients who were scheduled to undergo elective laparoscopic left colonic resection for cancer in two centers were reviewed by two radiologists blinded to clinical data for the presence of several key imaging features in order to assess general, cardiac, pulmonary, abdominal, renal, vascular and musculoskeletal status. CT examinations of patients from center 1 were used to build a CT-PS score to predict ASA-PS≥III. CT-PS score was further validated using an external cohort of patients from center 2. RESULTS: During a 2-year period, 117 consecutive patients (63 men, 54 women; mean age, 65±13 [SD] years; age range: 53-90 years) who underwent laparoscopic left colectomy for cancer in center 1 (66 patients, building cohort) and center 2 (51 patients, validation cohort) were retrospectively included. Ninety-one percent of patients were ASA-PS 1-2. Overall postoperative morbidity was 23% and severe morbidity 12%. The area under the receiver operating characteristic curve of CT-PS score was 0.968 (95% CI: 0.901-1.000) in the building cohort and 0.828 (95% CI: 0.693-0.963) in the validation cohort. The optimal thresholds yielded 87% (95% CI: 83-91%) sensitivity and 100% (95% CI: 91-100%) specificity in the building cohort and 75% (95% CI: 69-81%) sensitivity and 83% (95% CI: 77-88%) specificity in the validation cohort for the prediction of ASA-PS. CONCLUSION: Preoperative chest-abdomen-pelvis CT thoroughly and wisely read is highly accurate to differentiate patients with ASA-PS I/II from those with ASA-PS III/IV before left colectomy.

Surgical Management of Neuroendocrine Tumours of the Pancreas.

Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1-2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are 'functioning' when there is clinical hypersecretion of metabolically active peptides, whereas others are 'non-functioning'. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed.

Adrenalectomy during pregnancy: A 15-year experience at a tertiary referral center.

BACKGROUND: Adrenal lesions diagnosed during pregnancy remain rare, and their management is challenging because of maternal physiologic modifications, restricted imaging investigations, and contraindications to several treatments. Surgical issues of adrenalectomy during pregnancy and consequences on perinatal outcomes are poorly described. We therefore aimed to report maternal and fetal outcomes after adrenalectomy during pregnancy. METHODS: All pregnant women who underwent adrenalectomy over a 15-year inclusion period were identified from a prospectively maintained database. Surgical management and maternal and fetal outcomes were reviewed. RESULTS: From January 2003 to July 2018, a total of 12 women underwent adrenalectomy at a median gestation of 20 weeks. Of these women, 11 had hyper-secreting lesions, including 8 with cortisol oversecretion, and 11 had benign lesions, including cortisol-secreting adenoma (n = 5), pheochromocytoma (n = 2), primary pigmented, nodular adrenal disease (n = 1), severe Cushing's disease (n = 2), and hematoma (n = 1). A total of 3 patients with severe Cushing's disease (n = 2) and primary pigmented, nodular adrenal disease (n = 1) required bilateral adrenalectomy. One patient presented with a malignant adrenal Ewing sarcoma. Adrenalectomy during pregnancy was performed by the lateral laparoscopic transabdominal laparoscopic route in 9 patients. Postoperative morbidity occurred in 3 women. Maternal mortality was nil, but preterm birth occurred in 7 cases and intrauterine growth retardation was observed in 3 cases. Finally, among the 12 women, 10 had a child in good health. CONCLUSION: During pregnancy, a lateral laparoscopic transabdominal approach is a feasible procedure. Maternal outcome is acceptable but fetal outcome is determined by the underlying disease, with a worse outcome when the adrenalectomy is indicated for malignant lesions or Cushing's syndrome.

Study Protocol of the PreFiPS Study: Prevention of Postoperative Pancreatic Fistula by Somatostatin Compared With Octreotide, a Prospective Randomized Controlled Trial.

Background: Pancreatic fistula (PF), i. e., a failure of the pancreatic anastomosis or closure of the remnant pancreas after distal pancreatectomy, is one of the most feared complications after pancreatic surgery. PF is also one of the most common complications after pancreatic surgery, occurring in about 30% of patients. Prevention of a PF is still a major challenge for surgeons, and various technical and pharmacological interventions have been investigated, with conflicting results. Pancreatic exocrine secretion has been proposed as one of the mechanisms by which PF occurs. Pharmacological prevention using somatostatin or its analogs to inhibit pancreatic exocrine secretion has shown promising results. We can hypothesize that continuous intravenous infusion of somatostatin-14, the natural peptide hormone, associated with 10-50 times stronger affinity with all somatostatin receptor compared with somatostatin analogs, will be associated with an improved PF prevention. Methods: A French comparative randomized open multicentric study comparing somatostatin vs. octreotide in adult patients undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy with or without splenectomy. Patients with neoadjuvant radiation therapy and/or neoadjuvant chemotherapy within 4 weeks before surgery are excluded from the study. The main objective of this study is to compare 90-day grade B or C postoperative PF as defined by the last ISGPF (International Study Group on Pancreatic Fistula) classification between patients who receive perioperative somatostatin and octreotide. In addition, we analyze overall length of stay, readmission rate, cost-effectiveness, and postoperative quality of life after pancreatic surgery in patients undergoing PD. Conclusion: The PreFiPS study aims to evaluate somatostatin vs. octreotide for the prevention of postoperative PF.

Diverting Stoma for Refractory Ano-perineal Crohn's Disease: Is It Really Useful in the Anti-TNF Era? A Multivariate Analysis in 74 Consecutive Patients.

BACKGROUND AND AIMS: Faecal diversion [FD] can be proposed in patients with refractory anoperineal Crohn's disease [APCD]. This study aimed to assess long-term results of this strategy, following the advent of the anti-tumour necrosis factor [TNF] era. METHODS: All patients who underwent FD for refractory APCD between 2005 and 2017 were included, excluding patients with a history of ileal pouch-anal anastomosis. A multivariate analysis regarding absence of stoma reversal [SR] was performed. RESULTS: A total of 65 consecutive patients who underwent FD for APCD (comprising anoperineal fistula [n = 40, 62%], rectovaginal fistula [n = 21, 32%], fissures and/or ulceration [n = 9, 14%], and/or anal stricture [n = 5, 8%]) were included. At the time of FD, 34 patients [52%] presented with small bowel Crohn's disease [CD] involvement, 29 [45%] with colonic involvement, and 19 [29%] with rectal involvement. Following FD, 54 patients [83%] were treated with anti-TNF therapy, prescribed for isolated APCD [n = 10, 15%] or luminal CD with APCD [n = 44, 68%]. After a mean follow-up of 49 ± 29 [7-120] months, SR was not possible in 32 patients [49%], including 17 patients [26%] requiring a subsequent proctectomy with abdominoperineal excision. In multivariate analysis, rectal CD involvement was the only independent factor associated with a reduced rate of SR (odds ratio: 4.0 [1.153-14.000]; p = 0.029), and anti-TNF therapy had no impact on SR rate. CONCLUSIONS: FD can be performed in selected patients with refractory APCD, to avoid abdominoperineal resection. However, this strategy should be proposed with caution in patients presenting with rectal CD involvement. Anti-TNF therapy has no impact on SR rate.