Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

The safety of telemedicine clinics as an alternative to in-person preoperative assessment for elective laparoscopic cholecystectomy in patients with benign gallbladder disease: a retrospective cohort study.

BACKGROUND: The telemedicine clinic for follow up after minor surgical procedures in general surgery is now ubiquitously considered a standard of care. However, this method of consultation is not the mainstay for preoperative assessment and counselling of patients for common surgical procedures such as laparoscopic cholecystectomy. The aim of this study was to evaluate the safety of assessing and counselling patients in the telemedicine clinic without a physical encounter for laparoscopic cholecystectomy. METHODS: We conducted a retrospective analysis of patients who were booked for laparoscopic cholecystectomy for benign gallbladder disease via general surgery telemedicine clinics from March 2020 to November 2021. The primary outcome was the cancellation rate on the day of surgery. The secondary outcomes were complication and readmission rates, with Clavein-Dindo grade III or greater deemed clinically significant. We performed a subgroup analysis on the cases cancelled on the day of surgery in an attempt to identify key reasons for cancellation following virtual clinic assessment. RESULTS: We identified 206 cases booked for laparoscopic cholecystectomy from telemedicine clinics. 7% of patients had a cancellation on the day of surgery. Only one such cancellation was deemed avoidable as it may have been prevented by a face-to-face assessment. Severe postoperative adverse events (equal to or greater than Clavien-Dindo grade III) were observed in 1% of patients, and required re-intervention. 30-day readmission rate was 11%. CONCLUSIONS: Our series showed that it is safe and feasible to assess and counsel patients for laparoscopic cholecystectomy remotely with a minimal cancellation rate on the day of operation. Further work is needed to understand the effect of remote consultations on patient satisfaction, its environmental impact, and possible benefits to healthcare economics to support its routine use in general surgery.

Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery.

PURPOSE: We aimed at exploring indocyanine green (ICG) fluorescence wide spectrum of applications in hepatobiliary surgery as can result particularly useful in robotic liver resections (RLR) in order to overcome some technical limitations, increasing safety, and efficacy. METHODS: We describe our experience of 76 RLR performed between March 2020 and December 2022 exploring all the possible applications of pre- and intraoperative ICG administration. RESULTS: Hepatocellular carcinoma and colorectal liver metastases were the most common indications for RLR (34.2% and 26.7% of patients, respectively), and 51.3% of cases were complex resections with high IWATE difficulty scores. ICG was administered preoperatively in 61 patients (80.3%), intraoperatively in 42 patients (55.3%) and in both contexts in 25 patients (32.9%), with no observed adverse events. The most frequent ICG goal was to achieve tumor enhancement (59 patients, 77.6%), with a success rate of 94.9% and the detection of 3 additional malignant lesions. ICG facilitated evaluation of the resection margin for residual tumor and perfusion adequacy in 33.9% and 32.9% of cases, respectively, mandating a resection enlargement in 7.9% of patients. ICG fluorescence allowed the identification of the transection plane through negative staining in the 25% of cases. Vascular and biliary structures were visualized in 21.1% and 9.2% of patients, with a success rate of 81.3% and 85.7%, respectively. CONCLUSION: RLR can benefit from the routine integration of ICG fluoresce evaluation according to each individual patient and condition-specific goals and issues, allowing liver functional assessment, anatomical and vascular evaluation, tumor detection, and resection margins assessment.

Systematic review, meta-analysis and single-centre experience of the diagnostic accuracy of intraoperative near-infrared indocyanine green-fluorescence in detecting pancreatic tumours.

BACKGROUND: During pancreatic resections assessing tumour boundaries and identifying the ideal resection margins can be challenging due to the associated pancreatic gland inflammation and texture. This is particularly true in the context of minimally invasive surgery, where there is a very limited or absent tactile feedback. Indocyanine green (ICG) fluorescence imaging can assist surgeons by simply providing valuable real-time intraoperative information at low cost with minimal side effects. This meta-analysis summarises the available evidence on the use of near-infrared fluorescence imaging with ICG for the intraoperative visualization of pancreatic tumours (PROSPERO ID: CRD42021247203). METHODS: MEDLINE, Embase, and Web Of Science electronic databases were searched to identify manuscripts where ICG was intravenously administered prior to or during pancreatic surgery and reporting the prevalence of pancreatic lesions visualised through fluorescence imaging. RESULTS: Six studies with 7 series' reporting data on 64 pancreatic lesions were included in the analysis. MINOR scores ranged from 6 to 10, with a median of 8. The most frequent indications were pancreatic adenocarcinoma and neuroendocrine tumours. In most cases (67.2%) ICG was administered during surgery. ICG fluorescence identified 48/64 lesions (75%) with 81.3% accuracy, 0.788 (95%CI 0.361-0.961) sensitivity, 1 (95%CI 0.072-1) specificity and positive predictive value of 0.982 (95%CI 0.532-1). In line with the literature, ICG fluorescence identified 5/6 (83.3%) of pancreatic lesions during robotic pancreatic resections performed at our Institution. CONCLUSION: This meta-analysis is the first summarising the results of ICG immunofluorescence in detecting pancreatic tumours during surgery, showing good accuracy. Additional research is needed to define optimal ICG administration strategies and fluorescence intensity cut-offs.

Artificial intelligence in the diagnosis and management of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the third most common malignancy worldwide, with approximately 50% of patients developing colorectal cancer liver metastasis (CRLM) during the follow-up period. Management of CRLM is best achieved via a multidisciplinary approach and the diagnostic and therapeutic decision-making process is complex. In order to optimize patients' survival and quality of life, there are several unsolved challenges which must be overcome. These primarily include a timely diagnosis and the identification of reliable prognostic factors. Furthermore, to allow optimal treatment options, a precision-medicine, personalized approach is required. The widespread digitalization of healthcare generates a vast amount of data and together with accessible high-performance computing, artificial intelligence (AI) technologies can be applied. By increasing diagnostic accuracy, reducing timings and costs, the application of AI could help mitigate the current shortcomings in CRLM management. In this review we explore the available evidence of the possible role of AI in all phases of the CRLM natural history. Radiomics analysis and convolutional neural networks (CNN) which combine computed tomography (CT) images with clinical data have been developed to predict CRLM development in CRC patients. AI models have also proven themselves to perform similarly or better than expert radiologists in detecting CRLM on CT and magnetic resonance scans or identifying them from the noninvasive analysis of patients' exhaled air. The application of AI and machine learning (ML) in diagnosing CRLM has also been extended to histopathological examination in order to rapidly and accurately identify CRLM tissue and its different histopathological growth patterns. ML and CNN have shown good accuracy in predicting response to chemotherapy, early local tumor progression after ablation treatment, and patient survival after surgical treatment or chemotherapy. Despite the initial enthusiasm and the accumulating evidence, AI technologies' role in healthcare and CRLM management is not yet fully established. Its limitations mainly concern safety and the lack of regulation and ethical considerations. AI is unlikely to fully replace any human role but could be actively integrated to facilitate physicians in their everyday practice. Moving towards a personalized and evidence-based patient approach and management, further larger, prospective and rigorous studies evaluating AI technologies in patients at risk or affected by CRLM are needed.

Robotic central pancreatectomy: a systematic review and meta-analysis.

BACKGROUND: Central pancreatectomy is usually performed to excise lesions of the neck or proximal body of the pancreas. In the last decade, thanks to the advent of novel technologies, surgeons have started to perform this procedure robotically. This review aims to appraise the results and outcomes of robotic central pancreatectomies (RCP) through a systematic review and meta-analysis. METHODS: A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of RCP. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modelling. RESULTS: Thirteen series involving 265 patients were included. In all cases but one, RCP was performed to excise benign or low-grade tumours. Clinically relevant post-operative pancreatic fistula (POPF) occurred in 42.3% of patients. While overall complications were reported in 57.5% of patients, only 9.4% had a Clavien-Dindo score ≥ III. Re-operation was necessary in 0.7% of the patients. New-onset diabetes occurred postoperatively in 0.3% of patients and negligible mortality and open conversion rates were observed. CONCLUSION: RCP is safe and associated with low perioperative mortality and well preserved postoperative pancreatic function, although burdened by high overall morbidity and POPF rates.

The future of organ perfusion and re-conditioning.

Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization and improved initial graft function. Here, we summarize the latest findings and study the results of ex-vivo/ex-situ hypothermic (HMP) and normothermic machine perfusion (NMP) in the area of abdominal organ transplantation (kidney, liver, pancreas and intestine). We also consider the potential role of normothermic regional perfusion (NRP) to re-condition donors after circulatory death organs before retrieval. The findings from clinical studies reported to date suggest that machine perfusion will offer real benefits when compared with conventional cold preservation. Several randomized trials are expected to report their findings within the next 2 years which may shed light on the relative merits of different perfusion methods and could indicate which perfusion parameters may be most useful to predict organ quality and viability. Further work is needed to identify composite endpoints that are relevant for transplanted organs that have undergone machine preservation. Multi-centre trials to compare and analyse the combinations of NRP followed by HMP and/or NMP, either directly after organ retrieval using transportable devices or when back-to-base, are needed. The potential applications of machine preservation technology beyond the field of solid organ transplantation are also considered.

Contemporary outcomes of open repair of thoracoabdominal aortic aneurysm in young patients.

BACKGROUND: Endovascular technology now permits total endovascular thoracoabdominal aortic aneurysm (TAAA) repair with high volume centres reporting encouraging results. The long-term durability of such stent grafts is unknown, leading to concerns regarding their use in younger patients. This study reports contemporary outcomes of open repair in young patients. METHODS: Outcomes for patients age 60 or younger undergoing open TAAA repair between June 1999 and August 2013 with prospective collected data were analysed retrospectively. RESULTS: Thirty-seven patients (31 men, 84%) with a median age of 56 (range 22-60) were identified with a median TAAA diameter of 6.9 cm (range 5.6-11). Aneurysm aetiology included degenerative change (18), dilation of chronic dissection (10), connective tissue disease (7) and mycotic degeneration (2). Crawford Type IV TAAA were most commonly treated (17), followed by Type II (10), Type III (7) and Type I (3). Two (5%) patients died in hospital, one from multiple organ failure and one from respiratory failure. Three patients (8%) developed temporary paraplegia, all of whom made a complete recovery and 4 (11%) patients required temporary renal replacement therapy. Median critical care stay was 5 days (range 2-28) with an in-hospital stay of 14 days (range 7-83). During a median follow-up of 72 months (range 13-171), no patient subsequently required any further aneurysm related surgical or radiological intervention. The mean (SEM) survival time was 138.5 (11) months. The 5 year survival was 79.7% (8.3) including early deaths, with no aneurysm related complications. CONCLUSIONS: The outcome of open TAAA repair in patients aged less than 60 years is favorable. It is against these results that evolving endovascular interventions must be compared.

Outcomes following renal transplantation in older people: a retrospective cohort study.

BACKGROUND: The mean age of renal transplant recipients is rising, with age no longer considered a contraindication. Outcomes in older patients have not, however, been fully defined. The aim of our study is to evaluate outcomes in older people following renal transplantation at a Scottish regional transplant unit. METHODS: All renal transplants from January 2001 to December 2010 were analysed (n = 762). Outcomes following renal transplantation in people over 65 years old were compared to those in younger patients. Outcome measures were: delayed graft function (DGF), primary non-function (PNF), biopsy proven acute rejection (BPAR), serum creatinine at 1 year and graft and recipient survival. Lengths of initial hospital stay and re-admission rates were also assessed. Student's T-Test was used to analyse continuous variables, Pearson's Chi-Squared test for categorical variables and the Kaplan-Meier estimator for survival analysis. RESULTS: Older recipients received proportionately more kidneys from older donors (27.1% vs. 6.3%; p < 0.001). Such kidneys were more likely to have DGF (40.7% vs. 16.9%; p < 0.001). Graft loss at 1 year was higher in kidneys from older donors (15.3% vs. 7.6%; p = 0.04). There was no significant difference in patient survival at 1 year based on the age of the donor kidney. Recipient age did not affect DGF (16.9% vs. 18.5%; p = 0.77) or graft loss at 1 year (11.9% vs. 7.8%; p = 0.28). Older recipients were, however, more likely to die in the first year post transplant (6.8% vs. 2.1%; p = 0.03). BPAR was less common in older patients (6.8% vs. 22%; p < 0.01). Older recipients were more likely to be readmitted to hospital (31.8% vs. 10.9%; p < 0.001). CONCLUSIONS: Older patients experience good outcomes following renal transplantation and donor or recipient age alone should not preclude this treatment. An awareness of this in clinicians managing older patients is important since the prevalence of End Stage Renal Disease is increasing in this age group.