The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS. There were 101 patients with CPR after chemotherapy (n = 58, 57.4

Minimally invasive liver surgery (MILS) still appears to be adopted with significant variability. We aimed to investigate the diffusion, indications, and short-term outcomes of MILS compared to the open approach. A prospective registry of all liver resections performed for any indication and using any technique between January 1, 2017, and December 31, 2019, was established (BReLLS) and analyzed. A total of 1342 consecutive liver resections were included, 684 (51

Most studies on tumour progression from precursor lesion toward gallbladder adenocarcinoma investigate lesions sampled from distinct patients, providing an overarching view of pathogenic cascades. Whether this reflects the tumourigenic process in individual patients remains insufficiently explored. Genomic and epigenomic studies suggest that a subset of gallbladder cancers originate from biliary intraepithelial neoplasia (BilIN) precursor lesions, whereas others form independently from BilINs. Spatial transcriptomic data supporting these conclusions are missing. Moreover, multiple areas with precursor or adenocarcinoma lesions can be detected within the same pathological sample. Yet, knowledge about intra-patient variability of such lesions is lacking. To characterise the spatial transcriptomics of gallbladder cancer tumourigenesis in individual patients, we selected two patients with distinct cancer aetiology and whose samples simultaneously displayed multiple areas of normal epithelium, BilINs and adenocarcinoma. Using GeoMx digital spatial profiling, we characterised the whole transcriptome of a high number of regions of interest (ROIs) per sample in the two patients (24 and 32 ROIs respectively), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Human gallbladder organoids and cell line-derived tumours were used to investigate the tumour-promoting role of genes. Spatial transcriptomics revealed that each type of lesion displayed limited intra-patient transcriptomic variability. Our data further suggest that adenocarcinoma derived from high-grade BilIN in one patient and from low-grade BilIN in the other patient, with co-existing high-grade BilIN evolving via a distinct process in the latter case. The two patients displayed distinct sequences of signalling pathway activation during tumour progression, but Semaphorin 4 A (SEMA4A) expression was repressed in both patients. Using human gallbladder-derived organoids and cell line-derived tumours, we provide evidence that repression of SEMA4A promotes pseudostratification of the epithelium and enhances cell migration and survival. Gallbladder adenocarcinoma can develop according to patient-specific processes, and limited intra-patient variability of precursor and cancer lesions was noticed. Our data suggest that repression of SEMA4A can promote tumour progression. They also highlight the need to gain gene expression data in addition to histological information to avoid understimating the risk of low-grade preneoplastic lesions.

Background While outcomes after spleen-preserving distal pancreatectomy (SP-DP) have been widely reported, impacts on splenic parenchyma have not been well studied. This study aimed to compare postoperative outcomes, particularly spleen-related outcomes, by assessing splenic imaging after SP-DP with or without splenic vessels removal. Methods Data for all patients who underwent SP-DP with splenic vessels removal (Warshaw technique, WDP) or preservation (Kimura technique, KDP) between 2010 and 2022 in two tertiary centres were retrospectively analysed. Splenic ischemia and volume at early/late imaging and postoperative outcomes were reviewed. Results Eighty-seven patients were included, 51 in the WDP and 36 in the KDP groups. Median Charlson’s Comorbidity Index was significantly higher in the WDP group compared with the KDP group. Postoperative morbidity was similar between groups. There was more splenic ischemia at early imaging in the WDP group compared to the KDP group (55% vs. 14%, p = 0.018), especially severe ischemia (23% vs. 0%). Partial splenic atrophy was observed in 29% and 0% in the WDP and KDP groups, respectively (p = 0.002); no complete splenic atrophy was observed. Platelet levels at POD 1, 2 and 6 were significantly higher in the WDP group compared to KDP group. At univariate analysis, age, Charlson Comorbidity Index, platelet levels at POD 6, and early splenic infarction were prognostic factors for development of splenic atrophy. No episodes of overwhelming post-splenectomy infection or secondary splenectomy were recorded after a median follow-up of 9 and 11 months in the WDP and KDP groups, respectively. Conclusions Splenic ischemia appeared in one-half of patients undergoing SP-DP with splenic vessels removal at early imaging, and partial splenic atrophy in almost 30% at late imaging, without clinical impact or complete splenic atrophy. Age, Charlson Comorbidity Index, platelet levels at POD 6, and early splenic infarction could help to predict the occurrence of splenic atrophy.

Background: Large distal pancreatic tumors may involve the transverse or splenic flexure mesocolon. R0 resection of such lesions may be extended to the mesocolon. Interruption of the arc of Riolan may be difficult to assess especially in MIS.

3561 Background: CRC is a complex and heterogeneous disease, with the liver being the most frequent site of metastasis. Around 20% of patients will always progress exclusively in the liver. These patients may be candidates for more aggressive therapeutic procedures that will impact in their outcome. LIVERMET SURVEY Database (LMSD) is a prospective international database, focused on patients operated for CRC liver metastasis, whether resected or not, which purpose is to evaluate patient outcomes and prognostic factors for these resected patients. We propose to analyse all patients enrolled in the (LMSD) to better characterised those determinants that are associated with pLLD. Methods: We analyzed all patients included in the LMSD. Patients with relapse of their disease after the first liver surgery were selected. In order to test associations between hepatic only and extrahepatic metastasis, a univariate and multivariate logistic model was performed with the variables considered clinically more relevant. Imputation of missing data using the mice method (Multivariate Imputation via Chained Equations) was performed. All analyses were performed with R 4.1.1 software. Results: A total of 8715 patients out of 33581 (26%) included in the LMSD presented disease recurrence after a first liver surgery. During their oncological history, pLLD occurred in 1392 patients (16%), and extrahepatic relapse was presented in 7323 patients (84%). The characteristics of patients with pLLD were as follows: 58.4% patients presented synchronic disease, 20.2% had right sided primary tumor, 58.6% presented unilateral disease at time of first hepatic surgery and 20.4% of patients presented R1 surgery. In multivariant analysis, right sided and rectum (HR 0.82. p = 0.001), unilateral liver involvement (HR 0.74, p < 0.001) and > 3cm of diameter in greatest lesion with maximum of 3 lesions (HR 0.85, p = 0.02) were predictive determinants of extrahepatic disease. Only synchronic metastases (HR 1.29, p < 0.001) and male sex (HR 1.15, p = 0.028) were associated with pLLD. Molecular information according to RAS, BRAF and MSI status was not evaluable in a majority of patients since this item has been recently implemented in the questionnaire. Conclusions: This study confirms that about 16% of patients with LLD mCRC will be pLLD mCRC. Despite clinical determinants like synchronic metastatic disease, which is associated with pLLD, further analyses including molecular determinants are needed. Identifying those determinants of pLLD in a scenario where more extreme surgeries and liver transplantations are being considered is a great challenge that needs to be addressed.

Purpose: Surgical resection remains the cornerstone treatment for liver tumors. Local recurrence risk is determined by surgery radicality which forces significant parenchymal sacrifice or R1 resection in case of vascular involvement. Jump-graft between intra-parenchymal origin and superior stump HVR might be necessary to preserve remnant liver adequate outflow when radical surgery requires a resection at HCo. Methods: Monocentric retrospective analysis of intraoperative data and outcomes in 16patients who underwent HVR(2018-2021) was performed. After tumor dissection under ultrasound control, proximal and distal HV stumps were clamped and involved hepatocaval segment resected in single block. Reconstruction was performed by interposition of vascular graft between both stumps. Results: Patients presented with different conditions: liver metastasis (n=13), intrahepatic cholangiocarcinoma (n=1), hepatocellular carcinoma (n=2). Non-frozen ABO-compatible venous homograft (n=12), autologous peritoneal patch/tube (n=3), autologous veins (n=1) were used as jump-grafts. Median HV clamping duration was 63min(54-90min). Pedicular clamping was only performed when HVR was associated to IVC replacement(n=2). Double HVR was also performed (n=3). HVR patency at day7 was 94%(15/16), at 3months 81%(13/16). Median blood loss was 1100ml(837-1700ml), R0 resection was achieved in 13/16(81%). Severe morbidity (Clavien III-IV) reached 25%(4/16). Small for size syndrome was null. Day90 mortality was null. Conclusion: In our series, R0 resection rate was high as well as early and late graft patency. Morbi-mortality was acceptable. HVR technique allows replacement of a single or double HV without significant bleeding nor need for pedicle clamping (if not associated to IVC replacement). Therefore, HVR should be considered as a realistic option in parenchymal-sparing strategy or radical surgery.

3596 Background: Surgical resection of CRLM aims to maximize patient survival. However, recurrence rates remain high post-surgery. We previously reported the prognostic relevance of tumor regression grading (TRG) and HGP of resected CRLM. Several studies reported the association of tumoral heterogeneity with anti-cancer drug resistance and prognosis. This study aims to explore tumoral heterogeneity for TRG and HGP in patients resected for CRLM and its prognostic implication. Methods: Tumor homogeneity for PR and HGP was evaluated in 2 independent cohorts. Cohort 1 included 57 patients (159 CRLMs) resected after chemotherapy/bevacizumab (prospective BEV-ONCO trial). Cohort 2 included 221 patients (582 CRLMs) operated after preoperative treatment or not. TRG (1 to 5 according complete to no response), HGP (desmoplastic, pushing, replacement or mixed) were evaluated for each CRLM. Max-TRG (higher TRG among all the CRLM) was used to define PR. Homogenous TRG (TRG-h) and HGP (HGP-h) was defined when all CRLMs had the same TRG or HGP pattern. HGP homogeneous desmoplastic (HGP-hd) was defined when all CRLM had a desmoplastic HGP. TRG-h, HGP-h and HGP-hd were combined into a homogeneity score (H-score: 0 to 3, 1 point given for each parameter and summed-up). Overall survival (OS for both cohorts), progression-free survival (PFS for cohort 1) and time to relapse (TTR for cohort 2) were estimated using the Kaplan–Meier method and compared by log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. Results: Patient and disease characteristics were comparable in both cohorts excepted for preoperative treatment. In cohort 1, TRG-h and HGP-h were significantly associated with a longer PFS (HR = 0.21; 95CI:0.10-0.43, p < 0.001; HR = 0.27; 95CI = 0.14-0.54, p < 0.001) and better OS (HR = 0.23; 95CI = 0.07-0.70, p = 0.010; HR = 0.32; 95CI = 0.10-0.93, p = 0.037). Interestingly, the same significant results were observed in cohort 2 for TTR (TRG-h: HR = 0.60; 95CI = 0.43-0.85, p = 0.004; HGP-h: HR = 0.68; 95CI = 0.49-0.94, p = 0.017) and OS (TRG-h: HR = 0.51;95CI = 0.33-0.80, p = 0.003; HGP-h: HR = 0.63; 95CI = 0.41-0.97, p = 0.034). HGP-h reported a significant association with TRG-h, a Max-TRG < = 3, the absence of HGP replacement and mixed, a desmoplastic pattern, and the absence of sinusoidal obstruction syndrome in both cohorts. H-score was significantly associated with TTR (score 1-2: HR = 0.57; 95CI = 0.38-0.85, p = 0.004; score 3: HR = 0.4; 95CI = 0.24-0.64, p < 0.001) and OS (score 3: HR = 0.31; 95CI = 0.15-0.64, p < 0.001) in univariate analysis and with OS (HR = 0.74; 95CI = 0.59-0.94, p = 0.011) in multivariate analysis (cohort 2). Conclusions: TRG-h and HGP-h are strongly associated with patient’s survival. H-score could be an easy morphological and prognostic score to assess. Validation studies are needed.

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

Background The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). Conclusion In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

INTRODUCTION: Adrenocortical carcinoma is a rare type of malignant adrenal tumor with a possibility of delayed metastases. Diagnosis may be delayed with a non-secreting tumor or metastasis, and even in this case, surgical management may be complicate. PRESENTATION OF CASE: A 55-year-old man underwent elective surgery for the resection of a large intrahepatic mass from an undetermined type according to a recent liver biopsy. He had a previous history of a non-secreting adrenal tumor that was operated ten years before. Pre-operatively, he was poorly symptomatic, with a normal arterial blood pressure. Anesthesia induction was uneventful, but at the time of tumor resection and removal, he developed extreme vasoplegia and shock with anuric renal failure, lactic acidosis, four-limb and abdominal compartment syndrome. The patient died on day 9 from delayed septic complications. According to the pathological findings, the tumor was a non-secreting adrenocortical carcinoma. DISCUSSION: Adrenocortical carcinoma (ACC) is rare condition with diverse clinical manifestations due to excessive hormonal production when the tumor is secreting and mimicking pheochromocytoma. Our patient underwent the resection a large intrahepatic non-secreting metastasis more than ten years after the initial lesion. Peri-operative and post-operative management was complicated by a refractory shock with the characteristics of a secondary systemic capillary leak syndrome. The role of endothelial lesions may be discussed. CONCLUSION: Surgery of metastatic adrenocortical carcinoma may be complicated by severe hemodynamic complications, even in the absence of hormonal secretion. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Surgical resection of colorectal liver metastases combined with systemic treatment aims to maximize patient survival. However, recurrence rates are very high postsurgery. In order to assess patient prognosis after metastasis resection, we evaluated the main patho-molecular and immune parameters of all surgical specimens. Two hundred twenty-one patients who underwent, after different preoperative treatment, curative resection of 582 metastases were analyzed. Clinicopathological parameters, RAS tumor mutation, and the consensus Immunoscore (I) were assessed for all patients. Overall survival (OS) and time to relapse (TTR) were estimated using the Kaplan-Meier method and compared by log-rank tests. Cox proportional hazard models were used for uni- and multivariate analysis. Immunoscore and clinicopathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariate analysis. Overall, pathological score (PS) that combines relevant clinicopathological factors for relapse, and I, were prognostic for TTR (2-year TTR rate PS 0-1: 49.8.% (95% CI: 42.2-58.8) versus PS 2-4: 20.9% (95% CI: 13.4-32.8), hazard ratio (HR) = 2.54 (95% CI: 1.82-3.53), p < 0.0000; and 2-year TTR rate I 0: 25.7% (95% CI: 16.3-40.5) versus I 3-4: 60% (95% CI: 47.2-76.3), HR = 2.87 (95% CI: 1.73-4.75), p = 0.0000). Immunoscore was also prognostic for OS (HR [I 3-4 versus I 0] = 4.25, 95% CI: 1.95-9.23; p = 0.0001). Immunoscore (HR [I 3-4 versus I 0] = 0.27, 95% CI: 0.12-0.58; p = 0.0009) and RAS mutation (HR [mutated versus WT] = 1.66, 95% CI: 1.06-2.58; p = 0.0265) were significant for OS. In conclusion, PS including relevant clinicopathological parameters and Immunoscore permit stratification of stage IV colorectal cancer patient prognosis in terms of TTR and identify patients with higher risk of recurrence. Immunoscore remains the major prognostic factor for OS.

BACKGROUND:While distal pancreatectomy with splenectomy (DPS) is the reference treatment for pancreatic body and tail neoplasia, oncological benefits of splenectomy have never been demonstrated. Involvement of spleen, splenic hilum and lymph nodes (LN) was therefore assessed on DPS specimens. METHODS:All DPS pancreatic neoplasia specimens obtained in 2 Brussels University Hospitals over 15 years (2004-2018) were reviewed retrospectively, using both preoperative radiological imaging and postoperative pathological analyses of splenic parenchyma, hilar tissue and LN. RESULTS:The total of 130 DPS specimens included 85 adenocarcinomas, 37 neuroendocrine neoplasms and 8 other carcinomas. Tumours involved the pancreatic body without tail invasion for 59 specimens (B, Body group), and the pancreatic tail with/without body for 71 (T, Tail group). At pathology, direct splenic and/or hilar involvement was observed in 13 T specimens (13/71, 18.3%), but in none belonging to the Body group. The observed numbers of splenic hilar LN (only reported in 49/130 patients) were low, only one T adenocarcinoma had positive splenic LN in addition to direct splenic involvement. CONCLUSION:Splenectomy remains justified during pancreatectomy for neoplasia involving the pancreatic tail, but in case of pancreatic body tumours, its benefits should be questioned in the light of absent splenic LN/parenchymal involvement.

Background In the era of fast-track surgery, because pancreaticoduodenectomy (PD) carries a significant morbidity, surgeons hesitate to begin early oral feeding and achieve early discharge. We compared the outcome of two different approaches to the postoperative management of PD in two tertiary centers. Methods Of patients having undergone PD for malignancy from 2008 to 2017, 100 patients who received early postoperative oral feeding (group A) were compared to 100 patients from another center who received early enteral feeding and a delayed oral diet (group B). Surgical indication and approach and type of pancreatic anastomosis were similar between both groups. Postoperative outcomes were retrospectively reviewed. Results Patient characteristics were similar between both groups, except significantly more neoadjuvant treatment in group A (A = 20% vs. B = 9%,p < 0.01). Mortality rates were 3% and 4% in groups A and B, respectively (p = 0.71). The rate of severe postoperative morbidity was significantly lower in group A (13% vs. 26%,p = 0.02), resulting in a lower reoperation rate (p < 0.01). Delayed gastric emptying and clinically relevant pancreatic fistula were similar between both groups but chyle leaks were more frequent in group A (10% vs. 3%,p = 0.04). The median hospital stay was shorter in group A (16 vs. 20 days,p < 0.01). Conclusion In the present study, early postoperative oral feeding after PD was associated with a shorter hospital stay and did not increase severe postoperative morbidity or the rate of pancreatic fistula. However, it resulted in more chyle leaks and did not prevent delayed gastric emptying.

Background: Management of bile duct injury (BDI) after cholecystectomy is challenging. The authors analyzed their center's 49-year experience.Methods: From 1968 to 2016, 120 consecutive patients were managed in a tertiary HBP center, 105 referred from other centers (Group A), 15 from our center (Group B). Surgical strategies and long-term outcomes were retrospectively reviewed.Results: Primary cholecystectomy approach was open in 35% and laparoscopic in 65%. In Group A, intraoperative BDI diagnosis was made in 25/105 patients, including 13 via intraoperative cholangiography (IOC) which was used in 21% of cases. Median time from BDI to referral was 148 days (range 0-10,758), and 3 patients had BDI-related secondary cirrhosis. Ninety-four patients underwent secondary surgical repair, mostly a complex biliary procedure (97%). Postoperative overall and severe morbidity rates were 26% and 6%, respectively. One patient with biliary cirrhosis at referral died postoperatively from hepatic failure. Nine patients (9.6%) developed a secondary biliary stricture after a median of 54 months from repair (6-228 months). In Group B, IOC was performed in 14/15 in whom BDI were intraoperatively detected and immediately repaired. There were 13 minor and 2 major BDIs, all repaired by uncomplex procedures with uneventful postoperative course. One patient had a secondary biliary stricture after 5 months, successfully treated by temporary endoprosthesis.Conclusion: Late follow-up after primary or secondary repair of BDI is recommended to detect recurrent biliary stricture. Bile duct injuries may occur in a tertiary center, but are intraoperatively detected with routine IOC and immediately repaired resulting in satisfactory outcome.

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67+ tumor cells and CD3+ cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics.

Gallstone disease and related cholecystitis are common clinical conditions for which ultrasound is the diagnostic method of choice. Computed Tomography (CT) can help in difficult and inconclusive cases. We present a case of a patient with a final diagnosis of an entrapped gallstone causing subacute cholecystitis, detected first with a spectral CT and the use of the mean atomic number display map of the gallbladder content.