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Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child–Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC.

Introduction: Stereotactic MR-guided Adaptive RadioTherapy (SMART) is a novel process to treat pancreatic tumors. We present an update of the data from our prospective registry of SMART for pancreatic tumors. Materials and methods: After the establishment of the SMART indication in a multidisciplinary board, we included all patients treated for pancreatic tumors. Primary endpoints were acute and late toxicities. Secondary endpoints were survival outcomes (local control, overall survival, distant metastasis free survival) and dosimetric advantages of adaptive process on targets volumes and OAR. Results: We included seventy consecutive patients in our cohort between October 2019 and April 2022. The prescribed dose was 50 Gy in 5 consecutive fractions. No severe acute SMART related toxicity was noted. Acute and late Grade ≤ 2 gastro intestinal were low. Daily adaptation significantly improved PTV and GTV coverage as well as OAR sparing. With a median follow-up of 10.8 months since SMART completion, the median OS, 6-months OS, and 1-year OS were 20.9 months, 86.7% (95% CI: (75–93%), and 68.6% (95% CI: (53–80%), respectively, from SMART completion. Local control at 6 months, 1 year, and 2 years were, respectively, 96.8 % (95% CI: 88–99%), 86.5 (95% CI: 68–95%), and 80.7% (95% CI: 59–92%). There was no grade > 2 late toxicities. Locally Advanced Pancreatic Cancers (LAPC) and Borderline Resectable Pancreatic Cancers (BRPC) patients (52 patients) had a median OS, 6-months OS, and 1-year OS from SMART completion of 15.2 months, 84.4% (95% CI: (70–92%)), and 60.5% (95% CI: (42–75%)), respectively. The median OS, 1-year OS, and 2-year OS from initiation of induction chemotherapy were 22.3 months, 91% (95% CI: (78–97%)), and 45.8% (95% CI: (27–63%)), respectively. Twenty patients underwent surgical resection (38.7 % of patients with initially LAPC) with negative margins (R0). Conclusion: To our knowledge, this is the largest series of SMART for pancreatic tumors. The treatment was well tolerated with only low-grade toxicities. Long-term OS and LC rates were achieved. SMART achieved high secondary resection rates in LAPC patients.

Background There are no specific guidelines for ventral hernia management in Crohn’s disease (CD) patients. We aimed to assess the risk of septic morbidity after mesh repair in CD. Methods This was a retrospective multicentre study comparing CD and non-CD patients undergoing mesh repair for ventral hernia (primary or incisional hernia). Controls were matched 1:1 for the presence of a stoma, history of surgical sepsis, hernia size and Ventral Hernia Working Group (VHWG) score. All demographic, pre-, intra- and postoperative data were retrieved, including long-term data. Results We included 234 patients, with 114 CD patients. Both groups had comparable VHWG scores ( p  = 0.12), hernia sizes ( p  = 0.11), ASA scores ≥ 3 ( p  = 0.70), body mass index values ( p  = 0.14), presence of stoma (CD 21.9% vs. controls 15%, p  = 0.16), history of sepsis (14% vs. 6.7%, p  = 0.23), rates of malnutrition (4.4% vs. 1.7%, p  = 0.46), rates of incisional hernia (93% vs. 95%, p  = 0.68) and concomitant procedures (18.4% vs. 11.7%, p  = 0.12). CD patients carried a higher risk of postoperative septic morbidity (18.4% vs. 5%, p  = 0.001), entero-prosthetic fistula (7% vs. 0, p  < 0.01) and mesh withdrawals (5.3% vs. 0, p  = 0.011). Ventral hernia recurrence rates were similar (14% vs. 8.3%, p  = 0.15). In the univariate analysis, the risk factors for septic morbidity were CD ( p  = 0.001), malnutrition ( p  = 0.004), use of biological mesh ( p  < 0.0001) and concomitant procedure ( p  = 0.004). The mesh position, the means used for mesh fixation as well as the presence of a stoma were not identified as risk factors. Conclusions CD seems to be a risk factor for septic morbidity after mesh repair.

Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival. •Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) is common.•Recent studies showed that cure after resection of ICC seems to be an elusive goal.•Tumor size greater than 5 cm is an independent risk factor for recurrence.•Recurrence after resection of ICC is often beyond the limits of resectability.•A repeat liver resection (RLR) was feasible in only 25% of patients.•A RLR was associated with prolonged overall survival.

Cancer-associated fibroblasts (CAF) are important constituents of the tumor microenvironment (TME) and are major drivers of tumorigenesis. Yet, therapies aiming at eliminating CAF have failed to cure patients. This setback has raised questions regarding whether CAF exclusively favour cancer progression, or if they may also assume tumor-suppressor functions. In the present study, we used proteomics and single cell RNA-sequencing analysis to examine the CAF landscape in hepatocellular carcinoma (HCC). We thereby unveil three major CAF populations in HCC, one of which specifically expressing the prolargin protein. This CAF subpopulation (further termed as CAF_Port) shared a strong transcriptomic signature with portal liver fibroblasts. We further show that CAF_Port deposit prolargin in the TME and that its levels are lower in tumors as compared to the peritumoral region. Mechanistically, aggressive cancer cells degraded prolargin using matrix metalloprotease activity. Survival analysis of 188 patients revealed that high prolargin protein levels correlate with good patient outcome (HR = 0.37; p  = 0.01). In vivo, co-injection of cancer cells with fibroblasts silenced for prolargin, led to faster tumor development (5-fold; p  = 0.01), mainly due to stronger angiogenesis. Using protein-protein interaction study and structural modelling, we further demonstrate that prolargin binds and inhibits the activity of several pro-agiogenic proteins, including hepatocyte and fibroblast growth factors. In conclusion, prolargin is angiogenesis modulator and CAF-derived tumor suppressor in HCC. Stabilizing prolargin levels in the CAF_Port subpopulation may revert their tumor-antagonizing properties, warranting exploration in further pre-clinical studies.

Genomic information can help to identify colorectal tumors with high and low metastatic potential, thereby improving prediction of benefit of local and/or systemic treatment. Here we investigated chromosomal aberrations in relation to the different stages of the metastatic cascade: dissemination of tumor cells into the mesenteric vein, metastatic outgrowth in the liver, intravasation of the peripheral blood circulation, and development of further distant metastasis. Peripheral and mesenteric blood from colorectal cancer patients (n = 72) were investigated for circulating tumor cells, and DNA extracted from their primary tumors was subjected to array comparative genomic hybridization profiling. The results were validated with an independent set of primary colorectal tumors (n = 53) by quantitative reverse transcription PCR. Mesenteric intravasation and liver metastasis were correlated with losses of chromosomes 16p (72%), 16q (27%), and 19 (54%), gain along 1q31 (45%) and 20q (60%), tumor cell infiltration into the peripheral blood circulation, and further distant metastasis with gain of chromosome 8q (59%) and 12 (47%, < 0.01). Chromosome 12 gain was associated with poor overall survival in the initial (2.8 vs >7 years) and validation cohort (3.3 vs >6 years). The prospective study presented here is a hypothesis-generating study and confirmation with larger cohorts is required. This is the first study that investigated colorectal cancer in its different stages of metastasis in correlation with copy number changes of the primary tumor. This information might be helpful to identify patients with limited metastatic spread who may profit from liver metastasis resection and may lead to the discovery of new therapeutic targets.Microarray data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE82228.

Quantitative differences in signal transduction are to date an understudied feature of tumour heterogeneity. The MAPK Erk pathway, which is activated in a large proportion of human tumours, is a prototypic example of distinct cell fates being driven by signal intensity. We have used primary hepatocyte precursors transformed with different dosages of an oncogenic form of Ras to model subclonal variations in MAPK signalling. Orthotopic allografts of Ras-transformed cells in immunocompromised mice gave rise to fast-growing aggressive tumours, both at the primary location and in the peritoneal cavity. Fluorescent labelling of cells expressing different oncogene levels, and consequently varying levels of MAPK Erk activation, highlighted the selection processes operating at the two sites of tumour growth. Indeed, significantly higher Ras expression was observed in primary as compared to secondary, metastatic sites, despite the apparent evolutionary trade-off of increased apoptotic death in the liver that correlated with high Ras dosage. Analysis of the immune tumour microenvironment at the two locations suggests that fast peritoneal tumour growth in the immunocompromised setting is abrogated in immunocompetent animals due to efficient antigen presentation by peritoneal dendritic cells. Furthermore, our data indicate that, in contrast to the metastatic-like outgrowth, strong MAPK signalling is required in the primary liver tumours to resist elimination by NK (natural killer) cells. Overall, this study describes a quantitative aspect of tumour heterogeneity and points to a potential vulnerability of a subtype of hepatocellular carcinoma as a function of MAPK Erk signalling intensity.

Background Treatment of common bile duct stones (CBDS) includes laparoscopic cholecystectomy (LC) with either laparoscopic common bile duct exploration (LCBDE) or perioperative endoscopic retrograde cholangiopancreatography (ERCP). The main objective of this study was to identify predictive factors for the failure of upfront and exclusive surgical treatment by LCBDE. Methods This is a single-center, retrospective study on patients with CBDS and operated for LC between 2007 and 2019. The use of intra- or postoperative endoscopy for CBD clearance within 6 months after surgery was considered as failure of LCBDE. Predictors for the failure of LCBDE were investigated and outcomes were compared. Results Among 222 operated patients, LCBDE was successfully performed in 173 patients (78%) and 49 (22%) required ERCP with sphincterotomy (intraoperative ( n =29) or postoperative ( n =20)). Independent risk factors for surgical failure were male sex (OR: 2.525 (1.111–5.738); p =0.027), anesthesia induction time ≥ 4 p.m. (OR: 4.858 (1.731–13.631); p =0.003), pediculitis (OR: 4.147 (1.177–14.606); p =0.027), and thin CDB < 4mm (OR: 11.951 (3.562–40.097), p < 0.0001). Age, ASA score, cystic anatomy, presence of cholecystitis, and the surgeon’s experience were not identified as predictors for surgical failure. A general anesthesia number >1 (6% vs. 33%; p < 0.0001), length of initial stay (6 [1–42] vs. 8 [2–27], p =0.012), total length of hospitalization (6 [1–45] vs. 9 [2–27]; p =0.010), and the rate of emergency readmissions (3.5% vs. 12.2%; p =0.027) were significantly higher in the LCBDE failure group. Conclusions Upfront LCBDE for CBDS was associated with improved outcomes compared to intra-/postoperative ERCP recourse. Male sex, pediculitis, thin CBD, and surgery later than 4 p.m were associated with LCBDE failure and the need for endoscopic treatment. Registration Number and Agency The present retrospective study was approved by our local ethics committee and was declared on ClinicalTrials.gov (ID: NCT04467710).

BackgroundBenefits and cost-effectiveness of robotic approach for distal pancreatectomy (DP) remain debated. In this prospective study, we aim to compare the short-term results and real costs of robotic (RDP) and laparoscopic distal pancreatectomy (LDP).MethodsFrom 2011 until 2016, all consecutive patients underwent minimally invasive DP were included and data were prospectively collected. Patients were assigned in two groups, RDP and LDP, according to the availability of the Da Vinci® Surgical System for our Surgical Unit.ResultsA minimally invasive DP was performed in 38 patients with a median age of 61 years old (44–83 years old) and a BMI of 26 kg/m2 (20–31 kg/m2). RDP group (n = 15) and LDP group (n = 23) were comparable concerning demographic data, BMI, ASA score, comorbidities, malignant lesions, lesion size, and indication of spleen preservation. Median operative time was longer in RDP (207 min) compared to LDP (187 min) (p = 0.047). Conversion rate, spleen preservation failure, and perioperative transfusion rates were nil in both groups. Pancreatic fistula was diagnosed in 40 and 43% (p = 0.832) of patients and was grade A in 83 and 80% (p = 1.000) in RDP and LDP groups, respectively. Median postoperative hospital stay was similar in both groups (RDP: 8 days vs. LDP: 9 days, p = 0.310). Major complication occurred in 7% in RDP group and 13% in LDP group (p = 1.000). Ninety-days mortality was nil in both groups. No difference was found concerning R0 resection rate and median number of retrieved lymph nodes. Total cost of RDP was higher than LDP (13611 vs. 12509 €, p < 0.001). The difference between mean hospital incomes and costs was negative in RDP group contrary to LDP group (− 1269 vs. 1395 €, p = 0.040).ConclusionShort-term results of RDP seem to be similar to LDP but the high cost of RDP makes this approach not cost-effective actually.

Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1–2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are ‘functioning’ when there is clinical hypersecretion of metabolically active peptides, whereas others are ‘non-functioning’. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed.