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Aims: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. Methods: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. Results: A total of 600 patients were included. The median age was 53 (IQR 65–41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0–1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). Conclusion: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy. [ABSTRACT FROM AUTHOR]

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%. High frequency somatic mutations in genes not typically associated with cholangiocarcinoma included mTOR, ABL1 and NOTCH1. We identified non-synonymous mutation (p.Glu38del) in MAP3K9 in ten tumors, associated with increased peri-vascular invasion (Fisher's exact, p < 0.018). Mutation-enriched pathways were primarily immunological, including innate Dectin-2 (FDR 0.001) and adaptive T-cell receptor pathways including PD-1 (FDR 0.007), CD4 phosphorylation (FDR 0.009) and ZAP70 translocation (FDR 0.009), with overlapping HLA genes. We observed cancer-associated mutations in over half of our patients. Many of these mutations are not typically associated with cholangiocarcinoma yet may increase eligibility for contemporary targeted trials. We also identified a targetable MAP3K9 mutation, in addition to oncogenic and immunological pathways hitherto not described in any cholangiocarcinoma subtype. [ABSTRACT FROM AUTHOR]

Introduction: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. Objective: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. Methods: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). Results: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I–III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. Conclusion: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results. [ABSTRACT FROM AUTHOR]

Purpose: Appendiceal goblet cell carcinomas (aGCCs) are rare but aggressive tumours associated with significant mortality. We retrospectively reviewed the outcomes of aGCC patients treated at our tertiary referral centre. Methods: We analysed aGCC patients, diagnosed between 1990–2016, assessing the impact of completion surgery and tumour factors on survival. Survival was assessed using Kaplan–Meier analysis. Results: We identified 41 patients (23 F, 18 M); median age 61 (range 27–79) years. Mean tumour size was 10.5 (range 0.5–50) mm; most tumours were located in the appendiceal tip (n = 18, 45%). Appendicectomy was the index surgery in 32 patients, 24 of whom subsequently underwent completion surgery at median 3 (range 1.3–13.3) months later. Histology from completion surgery showed residual disease in 8 patients: nodal disease (n = 2) or residual tumour (n = 6). Index surgery for the rest was either colectomy (n = 7) or cytoreductive surgery plus intraperitoneal chemotherapy (CRS-HIPEC) (n = 1). Index and completion surgery had 0% mortality and 2.5% morbidity. Overall and recurrence-free survival were not significantly affected by tumour grade or completion surgery. Disease recurred in 9 patients after a median follow-up of 57.0 (4.6–114.9) months; 7 of these patients died during follow-up. Recurrences were treated with CRS-HIPEC (n = 1), palliative chemotherapy (n = 3) or supportive care (n = 5). Five- and ten- year overall survival were 85.3% and 62.3% respectively; 5-year and 10-year recurrence-free survival were 73.6% and 50.6%. Conclusion: The prognosis of aGCCs remains relatively poor. Completion surgery did not prevent recurrence or improve survival, but this needs to be verified with a larger patient cohort. The high mortality associated with tumour recurrence questions current treatment recommendations. [ABSTRACT FROM AUTHOR]

Background: Resection margin status is a known prognosticator in patients who undergo resection for hilar cholangiocarcinoma. However, the influence of an isolated positive circumferential margin on clinical outcome is unclear. Methods: Patients with resected de novo hilar cholangiocarcinoma from two European hepatobiliary centres (Medical University of Vienna and Aintree University Hospital, 2006–2016) were classified according to resection margin status (negative, surgically positive, isolated circumferentially positive) and investigated with respect to overall survival (OS), recurrence-free survival (RFS) and recurrence pattern. Results: Eighty-three (48 male/35 female) patients were enrolled. The median age was 64 years (range 33–80). The median follow-up was 21.7 months (range 0.3–92.4). Forty (48%) patients had negative resection margins, 25 (30%) had an isolated positive circumferential margin and 18 (22%) had a positive surgical margin. The 5-year OS rates in patients with negative, isolated positive circumferential and positive surgical resection margins were 47%, 33% and 0%, respectively. Median OS was 45.6, 32.7 and 14.5 months, respectively (log rank, P = 0.011). Upon multivariable Cox regression analysis, resection margin status and lymph node status remained statistically significant (P < 0.05). No difference with respect to RFS and recurrence pattern was found between the groups (P > 0.05). Conclusion: Our data show that these three resection margin types were associated with different clinical outcomes. Circumferential margin status may therefore serve as a novel prognostic biomarker. [ABSTRACT FROM AUTHOR]

Robot-assisted laparoscopic surgery is yet another modification of minimally invasive liver surgery. It is described as feasible and safe from the surgical point of view; however, oncological outcomes need to be adequately analysed to justify the use of this technique when resecting malignant liver tumours. We reviewed existing English medical literature on robot-assisted laparoscopic liver surgery. We analysed surgical outcomes and oncological outcomes. We analysed operative parameters including operative time, type of hepatectomy, blood loss, conversion rate, morbidity and mortality rates and length of stay. We also analysed oncological outcomes including completeness of resection (R status), recurrence, survival and follow-up data. A total of 582 patients undergoing robot-assisted laparoscopic liver surgery were analysed from 17 eligible publications. Only 5 publications reported survival data. The overall morbidity was 19% with 0.2% reported mortality. R0 resection was achieved in 96% of patients. Robotic liver surgery is feasible and safe with acceptable morbidity and oncological outcomes including resection margins. However, well-designed trials are required to provide evidence in terms of survival and disease-free intervals when performed for malignancy. [ABSTRACT FROM AUTHOR]

Opinion Statement: The role of physical interventions (surgical resection and surgical/radiological ablation) for liver metastases of colorectal cancer has changed dramatically over the last 10-15 years. Whereas in the 1990s, when only those patients with up to three unilobar metastases were considered for any form of such intervention, our present approach to these physical interventions is determined by how much viable disease-free liver can be preserved (most authorities accepting 25-30% disease-free future remnant liver volume) and the possibility of further such interventions if the disease recurs in the liver. There is increasing evidence that for smaller tumours (<3 cm diameter), ablation therapy may be therapeutically the equivalent of surgical resection and possibly safer in high-risk patients with multiple comorbidities. Therefore, we now consider the use of such ablation therapies (with or without surgical resection) to be clinically effective when treating patients with multiple bilobar metastases that have shown good radiologic response to prior systemic therapy. [ABSTRACT FROM AUTHOR]