Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Spleen-preserving pancreatectomy with removal of splenic vessels: impact on splenic parenchyma ?

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.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis.

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.

Metabolomic approaches for enzyme function and pathway discovery in bacteria.

Most of the chemical diversity present in the natural world derives from the incredible ability of enzymes to act on and control metabolism. Yet, thousands of enzymes have no defined function. The capacity to probe, investigate and assign previously unknown enzyme function with speed and confidence is therefore highly sought-after. Metabolomics is becoming a dominant player in the field of functional genomics and, when coupled with genetic tools and protein biochemistry techniques, has enabled unbiased, de novo annotation of orphan enzymes both in vitro and ex vivo. In this chapter, we describe two distinct experimental and analytical metabolomic methodologies used to reveal enzyme function. Activity-based metabolomic profiling (ABMP) is an in vitro technique that enables tracking of enzyme-induced changes in a complex metabolite extract. Global metabolomic profiling permits the comparison of extracted cellular metabolome of groups of samples (e.g., wild-type versus mutant bacteria). The methods we describe present the advantage of generating cell extracts containing a broad range of metabolites in their native states, which can then be used to identify substrates for orphan enzymes. This chapter aims to provide a guide for the use of these metabolomic techniques by scientists interested in identifying bona fide physiological substrates of orphan enzymes and the metabolic pathways they belong to.

In vitro elucidation of the crucial but complex oxidative tailoring steps in rufomycin biosynthesis enables one pot conversion of rufomycin B to rufomycin C.

The antimycobacterial peptides, rufomycins, have their antibiotic activity conferred by oxidative tailoring of the cyclic peptide. Here we elucidate the roles of cytochrome P450s RufS and RufM in regioselective epoxidation and alkyl oxidation respectively and demonstrate how RufM and RufS create a complex product profile dependent on redox partner availability. Finally, we report the in vitro one pot conversion of rufomycin B to rufomycin C.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry.

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.

Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore.

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.

Refractory shock during the anesthetic and surgical management of an intrahepatic tumor arising from the adrenal cortex: A case report.

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 intra-hepatic 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.

Distal pancreatectomy for pancreatic neoplasia: is splenectomy really necessary? A bicentric retrospective analysis of surgical specimens.

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.

Early Versus Late Oral Refeeding After Pancreaticoduodenectomy for Malignancy: a Comparative Belgian-French Study in Two Tertiary Centers.

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.

Long-term results of secondary biliary repair for cholecystectomy-related bile duct injury: results of a tertiary referral center.

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.

The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients.

Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. We quantified immune cell types of 603 whole-slide metastases and primary colorectal tumors from 222 patients. Primary lesions, and synchronous and metachronous metastases, had a heterogeneous immune infiltrate and mutational diversity. Small metastases had frequently a low Immunoscore and T and B cell score, while a high Immunoscore was associated with a lower number of metastases. Anti-epidermal growth factor receptor treatment modified immune gene expression and significantly increased T cell densities in the metastasis core. The predictive accuracy of the Immunoscore from a single biopsy was superior to the one of programmed cell death ligand 1 (PD-L1). The immune phenotype of the least-infiltrated metastasis had a stronger association with patient outcome than other metastases.

Evolution of Metastases in Space and Time under Immune Selection.

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.

Impact of biological agents on the prevalence of chemotherapy associated liver injury (CALI): Multicentric study of patients operated for colorectal liver metastases.

BACKGROUND: The prevalence of chemotherapy associated liver injuries (CALI), especially SOS (sinusoidal obstruction syndrome) and NRH (nodular regenerative hyperplasia) might be reduced since the introduction of routine use of biological agents with chemotherapy in colorectal liver metastases (CRLM). METHODS: One hundred patients with CRLM having undergone at least one liver segment resection were prospectively included, and chemotherapy data recorded. Specimens were reviewed by a single pathologist and CALI were described. Prevalence of CALI was compared to our previous experience published in 2013. NRH diagnosis was performed on reticulin special stain, by contrast to our previous study. Postoperative outcome was analysed. RESULTS: Bevacizumab was more frequently administrated in patients of the present study: 53/100 (53%) compared to 20/151 (13%), p < 0.0001. Overall, in the present series, SOS was only observed in 28/100 (28%) patients compared to 116/151 (77%) in 2013 (p < 0.001). When looking specifically to patients receiving Bevacizumab with Folfox, we observed a reduced SOS prevalence compared to Folfox alone (p = 0.008). A higher prevalence of NRH was found in the present study, related to increased detection accuracy, but in patients receiving Bevacizumab in association with Folfox, this prevalence was also reduced compared to Folfox alone (p = 0.03). Both SOS and NRH were associated with severe complications (p = 0.008 and p = 0.005, respectively) and postoperative liver insufficiency (p < 0.001 and p < 0.01, respectively). CONCLUSIONS: The routine use of Bevacizumab in association with Folfox significantly reduced CALI prevalence, in turn linked to severe postoperative complications.

How to optimize the prescription of laboratory tests? Success and failures in an academic hospital.

In the context of the flat-rate reimbursements in healthcare, we reviewed physicians' behavior towards laboratory test ordering. We demonstrated how it could be improved when a specific stage of the patient management is considered. We took a multi-step approach to analyze the laboratory test orders in the context of planned laparoscopic cholecystectomy in a general teaching hospital. A reference order set was defined through a collaborative analysis between clinicians and laboratory physicians. The clinical and financial impacts were then evaluated over a period of 24 months. After the introduction of the reference order set, the number of laboratory tests per order decreased significantly for patients with cholecystitis of low severity. Above the monitoring of repeated orderings during a single stay, the major impacts were achieved by a drastic reduction of inappropriate orders, particularly in the field of bacteriology. The main effects of the order set were maintained throughout a follow-up period of 24 months. Our study demonstrated that, when considering laboratory test ordering optimization, reference order sets could achieve high levels of efficiency. To ensure high compliance to reference order sets, extensive collaboration between clinicians and laboratory physician is mandatory even if very sophisticated information systems are available.

Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.

Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients.

PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.

Feasibility, safety and efficacy of two-stage hepatectomy for bilobar liver metastases of colorectal cancer: a LiverMetSurvey analysis.

BACKGROUND: The combination of liver resection and chemotherapy has become the standard of care for colorectal liver metastases (LM). The objective of the present study was to evaluate the impact of two-stage hepatectomy (TSH) on the long-term survival of patients with bilobar LM. METHODS: We included adult (over-18) patients from the LiverMetSurvey registry with confirmed multiple colorectal LM and having undergone either one-stage hepatectomy or TSH with curative intent. The "TSH (2/2)" group (n = 625) comprised patients having completed both stages of TSH; the "TSH (1/2)" group (n = 244) comprised patients having undergone only the first stage of TSH; the "hepatectomy" group. The primary outcome criterion was the overall survival (OS). The secondary outcomes were the morbidity and mortality rates. RESULTS: The 30- and 90-day mortality rates were respectively 3.8% and 9.3% in the TSH (2/2) group, 9.4% and 16.4% in the TSH (1/2) group, and 5.4% and 9.1% in the "hepatectomy" group. The three-year OS rate was 45% in the TSH (2/2) group, 30% in the TSH (1/2) group and 50.7% in the hepatectomy group. CONCLUSION: The LiverMetSurvey registry's data indicate that TSH is associated with rather good long-term survival and acceptable morbidity and mortality rates.

The practice of laparoscopic liver surgery in Belgium: a national survey.

BACKGROUND: Laparoscopic liver surgery (LLS) gained popularity bringing several advantages including decreased morbidity and reduction of length of hospital stay compared to open. METHODS: To understand practice and evolution of LLS in Belgium, a 20-questions survey was sent to all members of the Royal Belgian Society for Surgery, the Belgian Section of Hepato-Pancreatic and Biliary Surgery and the Belgian Group for Endoscopic Surgery. RESULTS: Thirty-seven surgical units representing 61 surgeons performing LLS in Belgium responded: 50% from regional hospitals, 28% from university and 22% from peripheral hospitals. Replies from high volume centers (>50 liver-surgery/year) were 19%. More than 25% of liver procedures were performed laparoscopically in 35% of centers. LLS is adopted since more than 15-years in 14.5% of centers with an increasing rate reported in 59%. Low relevance of LLS in the hospital organization (26.5%) and lack of time in surgical schedules (12%) or of specific training (9%) are the main barriers for further diffusion. More than 80% of the responders agreed to participate to a national prospective registry. CONCLUSION: LLS is mainly performed in experienced HPB units with an increasing interest in peripheral centers. A prospective national registry will be useful by providing real data in terms of indications, morbidity and overall evolution.

Outcomes Following First-line Endourologic Management of Ureteroenteric Anastomotic Strictures After Urinary Diversion: A Single-center Study.

OBJECTIVE: To assess the outcomes of patients following a first-line systematic endourologic procedure used to treat ureteroenteric anastomotic strictures (UEAS). MATERIALS AND METHODS: All data from patients treated using a first-line endourologic approach for UEAS between 2010 and 2015 were reviewed retrospectively. The following data were analyzed: age, type of urinary diversion, initial symptoms, surgical endoscopic approach (antegrade or retrograde), pre- and postoperative creatinine levels, and postoperative complications and outcomes. Follow-up visits occurred at 6 weeks, 3 months, and 6 months postoperatively, and at least annually thereafter. RESULTS: A total of 27 patients (median age: 62.5 years) were included. Overall, 28 UEAS were treated endoscopically (ileal conduit: n = 25; neobladder: n = 3). Most UEAS developed following radical cystectomy for bladder cancer (n = 19). Overall, the endoscopic approach was successful in 20 cases (71.4%). The UEAS length was >1 cm in 21 cases (75%). All UEAS of <1 cm were treated successfully (n = 7). There were three grade II and five grade III complications. The median follow-up period was 25 months. The median creatinine levels before surgery and at last follow-up were 1.3 mg/dL and 0.9 mg/dL, respectively. CONCLUSION: An endourologic procedure is a reasonable option for first-line treatment for UEAS and has promising functional outcomes and limited morbidity.