The influence of procedural volume on short-term outcomes for robotic pancreatoduodenectomy-a cohort study and a learning curve analysis.

BACKGROUND: An increasing number of robotic pancreatoduodenectomies (RPD) are reported, however, questions remain on the number of procedures needed for gaining technical proficiency in RPD. Therefore, we aimed to assess the influence of procedure volume on short-term RPD outcomes and assess the learning curve effect. METHODS: A retrospective review of consecutive RPD cases was undertaken. Non-adjusted cumulative sum (CUSUM) analysis was performed to identify the procedure volume threshold, following which before-threshold and after-threshold outcomes were compared. RESULTS: Since May 2017, 60 patients had undergone an RPD at our institution. The median operative time was 360 min (IQR 302.25-442 min). CUSUM analysis of operative time identified 21 cases as proficiency threshold, indicated by curve inflexion. Median operative time was significantly shorter after the threshold of 21 cases (470 vs 320 min, p < 0.001). No significant difference was found between before- and after-threshold groups in major Clavien-Dindo complications (23.8 vs 25.6%, p = 0.876). CONCLUSIONS: A decrease in operative time after 21 RPD cases suggests a threshold of technical proficiency potentially associated with an initial adjustment to new instrumentation, port placement and standardisation of operative step sequence. RPD can be safely performed by surgeons with prior laparoscopic surgery experience.

Association of artificial turf and concussion in competitive contact sports: a systematic review and meta-analysis.

OBJECTIVE: To determine the incidence of head injuries and concussion in contact sports, comparing natural grass with artificial turf surfaces. DESIGN: Systematic review and meta-analysis via the RevMan V.5.3 software. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All studies describing competitive contact sports played on both natural grass and artificial turf. The primary outcome measured was occurrence of head injury and concussion. DATA SOURCES: The databases include PubMed, Embase, Cochrane, Medline and Sport Discus. The last search took place on 23 May 2019. The Newcastle-Ottawa Quality Assessment Scale evaluated the methodological quality of the selected studies with a funnel plot designed to determine publication bias. Study screening and data extraction were performed by two independent reviewers. RESULTS: Initial screening generated 42 publications, with 12 meeting criteria for inclusion. Eight studies described concussion only. The rate ratio (RR) of head injury and concussion was less on artificial turf compared with natural grass (RR=0.89, 95% CI 0.77 to 1.04) as was the rate ratio of concussion only (RR=0.72, 95% CI 0.58 to 0.89). CONCLUSION: Analysis of published data demonstrates a decreased incidence of head injury and concussion when contact sports are played on artificial turf. This difference was most marked for sports such as rugby and American football. However, artificial turf has no association with the incidence of head injury or concussion while playing soccer.

Metastatic uveal melanoma: A valid indication for liver resection.

PURPOSE: Owing to its relative resistance to chemotherapeutics, prognosis following the diagnosis of metastatic uveal melanoma has remained disappointing. On this basis, liver resection in cases of isolated hepatic metastases has been postulated as a viable treatment option. Herein we performed an analysis of patients who underwent hepatic metastatectomy for uveal melanoma and compared their outcomes to those undergoing resection for colorectal cancer liver metastases (CRLM) in the same time period. METHODS: From 2008 to 2018, all patients referred to our unit with hepatic metastases were included for analysis. Performing a 3:1 matched cohort analysis, patients with metastatic uveal melanoma were matched for age, sex, operative approach, tumour number and size to those undergoing resection for CRLM. Clinicopathological data was sought from a prospectively maintained database and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Fifteen patients underwent hepatic metastasectomy for primary uveal melanoma. A further 45 patients undergoing hepatectomy for metastatic colorectal cancer acted as the control group. No in-hospital mortality was noted with four patients (26.6%) developing post-operative morbidity. The median follow-up period following melanoma resection was 27 months (range 5-211) with 1-, 3- and 5- year overall survival for this cohort of 86.6%, 53.3% and 40%, respectively. There was no difference in overall survival between the melanoma and CRLM group (p =0.80). CONCLUSION: In patients presenting with hepatic metastases from uveal melanoma, this present study supports the rationale to proceed to surgery with acceptable morbidity and mortality.

Contemporary role of liver transplantation for the treatment of cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is a dismal disease with limited management options. Surgical resection remains the only established treatment however, due to its inherent predilection to invade vascular structures, only a fraction of patients with CCA meet resection criteria at diagnosis. Furthermore, R0 margins, crucial to obtain optimum survival can often prove elusive. AREAS COVERED: This review discusses the evolution of liver transplant for CCA, following its introduction in the 1990 s with less than exemplary outcomes. While transplantation is not standard of care, emerging data has suggested a crucial role in prolonging survival of those with CCA. Here we analyze the current role of orthotopic liver transplantation (OLT) in cirrhotic and non-cirrhotic patients, in the setting of both intrahepatic CCA and hilar CCA in order to establish whether this is a judicious use of a precious resource. EXPERT OPINION: Liver transplant has a definite role in the treatment of CCA, as highlighted by ongoing clinical trials. A greater understanding of tumor biology coupled with results of current studies will help elucidate which patients will best benefit from OLT. While significant strides are being made to improve outcomes, this must be tempered with an understanding of the finite nature of liver grafts.

Prevalence and Sonographic Detection of Gallbladder Polyps in a Western European Population.

BACKGROUND: Gallbladder cancer is rare but associated with significant morbidity and mortality necessitating the early identification of premalignant and malignant lesions to improve overall prognosis. Despite limited evidence regarding the effectiveness of transabdominal ultrasound (US) in the detection of gallbladder polyps, it plays a key role in current European guidelines. The aim of this study was to investigate gallbladder polyp prevalence in a western European population and assess the diagnostic accuracy of transabdominal US. METHODS: Data from patients who underwent cholecystectomy for US detected gallbladder polypoid lesions at four hospitals in Ireland and the United Kingdom between 2010 and 2018 were retrospectively collected. Patient demographics, ultrasonographic, and histopathologic findings were analyzed. RESULTS: A total of 134 patients underwent cholecystectomy for US-detected gallbladder polyps. After histopathologic examination, pseudopolyps were found in 75 (56%) specimens with dysplastic or malignant polyps seen in only six (4.5%) specimens. Mean size for neoplastic polyps was 33 mm. The positive predictive value for US in detecting neoplastic polyps in this study was 4.5%, which is significantly lower than the 10%-15% reported previously. CONCLUSIONS: Although the prevalence of neoplastic polyps in this study is higher than in the previous literature, the distribution of pseudopolyps and true polyps is as expected. With all malignant polyps being >10 mm in diameter, these findings support the current size thresholds stated in European guidelines. The poor diagnostic accuracy of US demonstrated may have led to significant number of patients undergoing unnecessary surgical intervention, further supporting the argument for improved strategies for the investigation of gallbladder polyps.

Chemotherapy and repeat resection abrogate the prognostic value of neutrophil lymphocyte ratio in colorectal liver metastases.

BACKGROUND: Evolution in surgical and oncological management of CRLM has called into question the utility of clinical risk scores. We sought to establish if neutrophil lymphocyte ratio (NLR) has a prognostic role in this patient cohort. METHODS: From 2005 to 2015,379 hepatectomies were performed for CRLM, 322 underwent index hepatectomy, 57 s hepatectomies were performed. Clinicopathological data were obtained from a prospectively maintained database. Variables associated with longterm survival following index and second hepatectomy were identified by Cox regression analyses and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Following index hepatectomy 1-,3-and 5-year survival was 90.7%, 68.1% and 48.6%. Major resection, positive margins and >5 tumours were negatively associated with survival. Those with elevated NLR(>5) had a median survival of 55 months, compared to 70 months with lower NLR(p = 0.027). Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (p = 0.93). Furthermore, NLR >5 had no impact on prognosis following repeat hepatectomy. Tumour diameter >5 cm (p = 0.04) was the sole predictor of poorer survival (p = 0.049). CONCLUSION: Despite elevated NLR correlating with shorter survival following index hepatectomy, this effect is negated by neoadjuvant chemotherapy and second hepatectomy for recurrent disease. This data would not support the use of NLR in the preoperative decision algorithm for patients with CRLM.

Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis.

Colorectal cancer is the third most common malignancy worldwide, with 1.3 million new cases annually. Metastasis to the liver is a leading cause of mortality in these patients. In human liver, metastatic cancer cells must evade populations of liver-resident natural killer (NK) cells with potent cytotoxic capabilities. Here, we investigated how these tumors evade liver NK-cell surveillance. Tissue biopsies were obtained from patients undergoing resection of colorectal liver metastasis (CRLM, n = 18), from the tumor, adjacent tissue, and distal resection margin. The number and phenotype of liver-resident NK cells, at each site, were analyzed by flow cytometry. Tumor-conditioned media (TCM) was generated for cytokine and metabolite quantification and used to treat healthy liver-resident NK cells, isolated from donor liver perfusate during transplantation. Liver-resident NK cells were significantly depleted from CRLM tumors. Healthy liver-resident NK cells exposed to TCM underwent apoptosis in vitro, associated with elevated lactate. Tumor-infiltrating liver-resident NK cells showed signs of mitochondrial stress, which was recapitulated in vitro by treating liver-resident NK cells with lactic acid. Lactic acid induced apoptosis by decreasing the intracellular pH of NK cells, resulting in mitochondrial dysfunction that could be prevented by blocking mitochondrial ROS accumulation. CRLM tumors produced lactate, thus decreasing the pH of the tumor microenvironment. Liver-resident NK cells migrating toward the tumor were unable to regulate intracellular pH resulting in mitochondrial stress and apoptosis. Targeting CRLM metabolism provides a promising therapeutic approach to restoring local NK-cell activity and preventing tumor growth.

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis.

BACKGROUND: Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. METHODS: Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections. RESULTS: Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM. CONCLUSIONS: The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis.

Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. METHODS: From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. RESULTS: Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. CONCLUSION: In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to -surgery with comparable morbidity and mortality rates to -isolated hepatectomy.

The e-handover: applications for surgical training.

BACKGROUND: Workplace-based assessments introduced in part to compensate for the reduced 'hands on' experience of surgical trainees are now a compulsory facet of surgical training. Taking the form of 'tick box' exercises they largely focus on procedural competence. This work aimed to ascertain whether a standardised electronic handover could also be used as a surrogate marker of trainees' diagnostic skills. METHODS: All data inputted by surgical trainees 'on call' were collected prospectively and saved in an encrypted database within the Department of Surgery. Presumptive diagnoses made by the admitting trainee over a 2-year time period were then compared with the discharge diagnosis as recorded on the hospital's computer system. RESULTS: Seventeen surgical trainees were analysed over the study time period, with 936 patients requiring in-patient admission suitable for inclusion. An improvement in trainees' diagnostic accuracy was noted over a 6-month period (p = 0.047). Further subgroup analysis demonstrated increased accuracy amongst trainees with general surgical posts as opposed to urology trainees (p = 0.046), and increased accuracy with increased workload (p = 0.042). CONCLUSION: The e-handover has real potential as an adjunct to established assessment tools currently in use and may provide the stimulus for valuable feedback to trainees. [Can a] standardised e-handover also be used as a surrogate marker of trainees' diagnostic skills?

Portopulmonary hypertension: Still an appropriate consideration for liver transplantation?

Liver transplantation (LT) in patients with portopulmonary hypertension (PoPH) has historically resulted in unpredictable and often poor outcomes. The United Kingdom experience for the period 1992-2012 is reported in this article. A retrospective analysis of patients, preoperatively fulfilling the PoPH European Respiratory Society Task Force on Pulmonary-Hepatic Vascular Disorders diagnostic criteria was conducted across all UK LT centers. Data collection included comorbidities, use of preoperative and postoperative pharmacotherapy, patient survival, and cause of death. To enable survival stratification, PoPH was classified as mild, moderate, or severe based on mean pulmonary pressure of <35 mm Hg, 35-49 mm Hg, and ≥50 mm Hg, respectively. Of 127 patients reported to have PoPH, just 28 fulfilled the diagnostic criteria (14 mild, 9 moderate, 5 severe). Twenty (71.4%) patients were male with median age and Model for End-Stage Liver Disease of 50 years (range, 23-62 years) and 18 (range, 6-43), respectively. Twelve (42.9%) patients died within 5 years of LT. The majority of deaths (10 of 12; 83%) occurred within the first 6 months after LT, aetiologies of which included right heart failure (n = 3), progressive PoPH (n = 2), and sepsis (n = 2). Of those receiving preoperative pharmacotherapy (n = 8), 5 are currently alive and were classified as mild to moderate PoPH. Both severe PoPH patients optimized preoperatively with pharmacotherapy died within a year of LT. Development of effective vasodilatory therapies in the setting of pulmonary arterial hypertension has led to a dramatic improvement in patient survival. The available data indicate that in this era of pharmacotherapy, PoPH in isolation no longer represents a valid consideration to transplant. Liver Transplantation 22 1637-1642 2016 AASLD.

FDG-PET/CT in the staging of local/regional metastases in breast cancer.

Breast cancer is the commonest female malignancy in the Western world and the most reliable predictor for survival is axillary lymph node metastases. Conventional staging techniques employed in breast cancer include mammography, ultrasonography, isotope bone scanning, sentinel lymph node biopsy, axillary lymph node dissection and magnetic resonance imaging. More recently FDG-PET and FDG-PET/CT have been used to complement the above methods. This review assesses the role of FDG-PET/CT in axillary staging in patients with primary breast cancer. A PubMed search was conducted and all articles containing relevant or new information were included. Relevant studies examined identified that FDG-PET/CT has a sensitivity of 60% and a specificity of 97% in detecting lymphatic metastasis. Although positive axillary FDG-PET/CT is a good predictor of axillary disease and correlates well with SLNB, the relatively poor sensitivity (60%) must be considered for treatment planning.