Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study.

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Pancreaticoduodenectomy in a patient with severe portal hypertension: the role of preoperative TIPS.

The complication rate for Pancreaticoduodenectomy (PD) is 40-50% in most published series and mortality can raise up to 4-5% even in high-volume centers. Severe portal hypertension secondary to liver disease is associated to high perioperative mortality and therefore is considered a contraindication for PD. No standardized management exists for surgically resectable patients with periampullary cancer and severe portal hypertension. The aim of this case study is to analyse the treatment alternatives in patients with periampullary cancer and severe portal hypertension and focus into the surgical treatment of these patients. We present the case of a 67 year-old patient case with a resectable ampullary cancer and portal hypertension managed with Preoperative Transjugular Intrahepatic Portosystemic Shunt (TIPS) to allow a PD. We present a literature review on the use of preoperative TIPS in patients who are candidates to PD. Neoadjuvant TIPS can be safely used in selected patients with severe portal hypertension who need a PD.

Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study.

BACKGROUND: International guidelines recommend monitoring of the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. MATERIALS AND METHODS: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and in high-risk groups. RESULTS: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared to LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 minutes,P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI>25 kg/m2, previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. CONCLUSION: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with less conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study.

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.

Robotic versus laparoscopic distal pancreatectomy for pancreatic adenocarcinoma in obese patients.

BACKGROUND: Robotic distal pancreatectomy (RDP) is associated with a lower conversion rate and less blood loss than laparoscopic distal pancreatectomy (LDP). LDP has similar oncological outcomes as open surgery in PDAC. The aim of this study was to compare perioperative and oncological outcomes in obese patients with RDP versus LDP for PDAC. MATERIALS AND METHODS: Retrospectively, all obese patients who underwent RDP or LDP for PDAC between 2012 and 2022 at 12 international expert centres were included. RESULTS: out of 372, 81 patients were included. All baseline features were comparable between the two groups. RDP was associated with decreased blood loss (495mlLDP vs. 188mlRDP; p = 0.003), lower conversion rate (13.5%RDP vs. 36.4%LDP; p = 0.019) and lower rate of Clavien-Dindo ≥3 complications (13.5%RDP vs. 36.4%LDP; p = 0.019). Overall and disease-free survival were comparable. CONCLUSIONS: In obese patients with left-sided PDAC, the robotic approach was associated with improved intraoperative outcomes and fewer severe complications.

Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study.

Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.

Robotic versus laparoscopic distal pancreatectomy in obese patients.

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.

Incisional Hernia Following Open Pancreaticoduodenectomy: Incidence and Risk Factors at a Tertiary Care Centre.

(1) Background: Incisional hernia (IH) is one of the most common complications following open abdominal surgery. There is scarce evidence on its real incidence following pancreatic surgery. The purpose of this study is to evaluate the incidence and the risk factors associated with IH development in patients undergoing pancreaticoduodenectomy (PD). (2) Methods: We retrospectively reviewed all patients undergoing PD between 2014 and 2020 at our centre. Data were extracted from a prospectively held database, including perioperative and long-term factors. We performed univariate and multivariate analysis to detect those factors potentially associated with IH development. (3) Results: The incidence of IH was 8.8% (19/213 patients). Median age was 67 (33-85) years. BMI was 24.9 (14-41) and 184 patients (86.4%) underwent PD for malignant disease. Median follow-up was 23 (6-111) months. Median time to IH development was 31 (13-89) months. Six (31.5%) patients required surgical repair. Following univariate and multivariate analysis, preoperative hypoalbuminemia (OR 3.4, 95% CI 1.24-9.16, p = 0.01) and BMI ≥ 30 kg/m2 (OR 2.6, 95% CI 1.06-8.14, p = 0.049) were the only factors independently associated with the development of IH. (4) Conclusions: The incidence of IH following PD was 8.8% in a tertiary care center. Preoperative hypoalbuminemia and obesity are independently associated with IH occurrence following PD.

Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study.

INTRODUCTION: Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. MATERIALS AND METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. RESULTS: Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). CONCLUSION: In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

Intraoperative indocyanine green clearance in liver surgery: a useful tool to promote parenchymal preservation?

A 66-year-old woman was diagnosed with sigmoid carcinoma with bilobar unresectable liver metastases. Primary tumor resection was performed. Neoadjuvant chemotherapy was administered to downstage liver disease. Following FOLFOX/panitumumab (4 cycles), disease progression was observed within the liver. Therefore, chemotherapy regimen was switched to FOLFIRI/cetuximab (12 cycles). At restaging, 7 out of 10 metastases showed complete radiologic response and 3 showed disease progression. Selective internal radiation therapy (SIRT) with Yttrium-90 was performed on these 3 metastases with very good local radiologic response. Surgical resection with curative intent was attempted.  ICG was administered 72 hours before surgery to help localization of liver metastases. Intraoperatively, very poor ICG clearance was demonstrated and therefore parenchyma-sparing resections were performed (segment II, III, IV and VII). At final histology, major pathologic response was observed with steatosis of the liver parenchyma. Postoperative course was uneventful and adjuvant capecitabine was administered (8 cycles). No recurrence was demonstrated at 38 months follow-up. However, eighteen months following surgery, she developed impairment of hepatic function and portal hypertension. Conclusion: Preoperative ICG administration could be helpful to intraoperatively detect patients that can develop late post hepatectomy impairment of hepatic function, especially following SIRT2 (REF2), and promote parenchymal preservation.

Pancreatic Cancer Surveillance in Carriers of a Germline Pathogenic Variant in CDKN2A.

Three percent of patients with pancreatic ductal adenocarcinoma (PDAC) present a germline pathogenic variant (GPV) associated with an increased risk of this tumor, CDKN2A being one of the genes associated with the highest risk. There is no clear consensus on the recommendations for surveillance in CDKN2A GPV carriers, although the latest guidelines from the International Cancer of the Pancreas Screening Consortium recommend annual endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) regardless of family history. Our aim is to describe the findings of the PDAC surveillance program in a cohort of healthy CDKN2A GPV heterozygotes. This is an observational analysis of prospectively collected data from all CDKN2A carriers who underwent screening for PDAC at the high-risk digestive cancer clinic of the "Hospital Clínic de Barcelona" between 2013 and 2021. A total of 78 subjects were included. EUS or MRI was performed annually with a median follow-up of 66 months. Up to 17 pancreatic findings were described in 16 (20.5%) individuals under surveillance, although most of them were benign. No significant precursor lesions were identified, but an early PDAC was detected and treated. While better preventive strategies are developed, we believe that annual surveillance with EUS and/or MRI in CDKN2A GPV heterozygotes may be beneficial.

Percutaneous transhepatic biliary drainage for biliary obstruction in perihilar cholangiocarcinoma: a 10-year analysis of safety and outcomes using the CCI index.

PURPOSE: To evaluate percutaneous transhepatic biliary drainage (PTBD) safety and efficacy in patients with perihilar cholangiocarcinoma (PCCA). METHODS: This retrospective observational study included patients with PCCA and obstructive cholestasis referred for a PTBD in our institution between 2010 and 2020. Technical and clinical success rates and major complication and mortality rates one month after PTBD were used as main variables. Patients were divided and analyzed into two groups: > 30 and < 30 Comprehensive Complication Index (CCI). We also evaluated post-surgical outcomes in patients undergoing surgery. RESULTS: Out of 223 patients, 57 were included. Technical success rate was 87.7%. Clinical success at 1 week was 83.6%, before surgery 68.2%, 80.0% at 2 weeks and 86.7% at 4 weeks. Mean total bilirubin (TBIL) values were 15.1 mg/dL (baseline), 8.1 mg/dL one week after PTBD), 6.1 mg/dL (2 weeks) and 2.1 mg/dL (4 weeks). Major complication rate was 21.1%. Three patients died (5.3%). Risk factors for major complications after the statistical analysis were: Bismuth classification (p = 0.01), tumor resectability (p = 0.04), PTBD clinical success (p = 0.04), TBIL 2 weeks after PTBD (p = 0.04), a second PTBD (p = 0.01), total PTBDs (p = 0.01) and duration of drainage (p = 0.03). Major postoperative complication rate in patients who underwent surgery was 59.3%, with a median CCI of 26.2. CONCLUSION: PTBD is safe and effective in the management of biliary obstruction caused by PCCA. Bismuth classification, locally advanced tumors, and failure to achieve clinical success in the first PTBD are factors related to major complications. Our sample reported a high major postoperative complication rate, although with an acceptable median CCI.

Development of a preoperative score to predict surgical difficulty in liver transplantation.

BACKGROUND: A difficulty score to predict intraoperative surgical complexity in liver transplantation has never been developed. The aim of this study was to assess factors associated with a difficult liver transplant and develop a score to predict difficult surgery. METHODS: All patients undergoing deceased donor whole liver transplantation from 2012 to 2019 at a single center were included. Estimated intraoperative blood loss (mL/kg) and surgery duration (skin-to-arterial reperfusion time) were used as surrogates of difficulty. Based on these variables, the study population was divided into 2 groups: high risk and standard risk of difficulty. Univariate and multivariate analyses were performed to identify predictors associated with a demanding liver transplantation and develop a difficulty score. RESULTS: A total of 515 patients were included in the study population, and 101 (20%) were considered difficult operations. Patients with a higher risk of difficulty showed a significantly higher rate of Clavien-Dindo ≥III complications (50.5% vs 24.4%, P = .001) and a longer hospital stay (19 vs 16 days, P = .001). Preoperative factors associated with difficulty were retransplantation (odds ratio 4.34, P = .001), preoperative portal vein thrombosis (odds ratio 3.419, P = .001), previous upper abdominal surgery (odds ratio 2.161, P = .003), spontaneous bacterial peritonitis (odds ratio 1.985, P < .02), and prior variceal bleeding (odds ratio 1.401, P = .051). A 10-point difficulty score was created, showing a negative predictive value of 84% at 4 points. CONCLUSION: Difficult liver transplantation surgery, as assessed by skin-to-arterial reperfusion time and estimated blood loss, is associated with worse perioperative outcomes. We developed a simple score with clinical preoperative variables that predicts difficult surgery, and therefore, it may help to optimize allocation policies and perioperative logistics.

Impact of microscopic incomplete resection for colorectal liver metastases on surgical margin recurrence: R1-Contact vs R1 < 1 mm margin width.

BACKGROUND: Several studies highlighted an inferior outcome of R1 resection for colorectal cancer liver metastases (CRLM); it is still unclear whether directly involved margins (R1-contact) are associated with a poorer outcome compared to R1 < 1 mm. The aim of this study is to analyze the impact on surgical margin recurrence (SMR) of R1-contact vs R1 < 1 mm patients. METHODS: Patients who underwent surgery for CRLM between 2009-2018 with both R1 resections on final histology were included and compared in terms of recurrence and survival. Factors associated with SMR were assessed by univariate and multivariate analysis. RESULTS: Out of 477, 77 (17.2%) patients showed R1 resection (53 R1-Contact and 24 R1 < 1 mm). Overall recurrence rate was 79.2% (R1 < 1 mm = 70.8% vs R1-contact group = 83%, P = .222). Median disease-free survival (DFS) and disease-specific survival (DSS) were significantly higher in R1 < 1 mm vs R1-contact group (93 vs 55 months; P = .025 and 69 vs 46 months; P = .038, respectively). The SMR rate was higher in R1-contact compared to R1 < 1 mm group (30.2% vs 8.3%; P = .036). At univariate analysis, age, number of metastases, open surgical approach, RAS status, and R1-contact were associated with SMR. At multivariate analysis, R1-contact margin was the only factor independently associated with higher SMR (OR = 5.6; P = .046). CONCLUSIONS: R1-contact margin is independently associated with SMR after liver resection for CRLM. Patients with R1-contact margin will also experience poorer DFS and DSS.

Preclinical testing of oncolytic adenovirus sensitivity in patient-derived tumor organoids.

Patient-derived organoids (PDOs) have shown the potential to reflect patient sensitivity to chemotherapeutic or targeted drugs. Recently, we showed that organoid models can also serve as a platform to screen for selectivity and potency of oncolytic adenoviruses (OAds). In this protocol, we describe the steps for tumor organoid adenoviral infection and functional assessment of patient-specific responses to OAds. We provide methods to determine OAd relative efficacy by evaluation of PDO viability after infection and adenoviral replication within cancer cells. For complete details on the use and execution of this protocol, please refer to Raimondi et al. (2020).

Microwave ablation of colorectal liver metastases: Impact of a 10-mm safety margin on local recurrence in a tertiary care hospital.

Microwave ablation (MWA) for colorectal liver metastasis (CLM) has been traditionally considered inferior to surgery due to the higher rate of local recurrence. The study investigated whether a safety margin of 10 mm can improve local control in patients undergoing surgical MWA. Surgical MWA was used to treat 53 lesions in 22 patients with CLM at our Institution from June 2012 to June 2017. The patients' mean age was 64.5 years, and the median size of the lesion was 16.5 mm (9-34 mm). MWA was associated with liver resection in 16 patients (72.7%). The median follow-up was 32.4 months. Univariate and multivariate analyses were performed to identify factors associated with tumor recurrence. Median ablation area was 36.6 mm2 (30-50 mm2). The complication rate was 22.7%. No local recurrence was observed during follow-up. Disease-free survival was 20 months (4.8-55.2 months). Univariate analysis revealed that the number of liver metastases and node-positive primary tumors were associated with tumor recurrence. Multivariate analysis revealed that node-positive primary tumor was the only factor significantly associated with tumor recurrence (p = 0.049; odds ratio, 12; 95% confidence interval, 1-143). When performed with a 10-mm safety margin, surgical MWA can lead to acceptable oncological outcomes with low morbidity. Therefore, it represents a good option in selected patients with CLM.