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Background Intraductal papillary neoplasm of the bile duct (IPNB) or biliary papillomatosis is a precursor lesion of papillary cholangiocarcinoma. 1 IPNB is recognized as a biliary counterpart of IPMN (pancreatic intraductal papillary mucinous neoplasm). IPNB is a rare disease involving entire (diffuse type) or one part (localized type) of biliary tree. Patients without distant metastasis are considered for surgical resection. For patients with distal bile duct papillomatosis, pancreaticoduodenectomy (PD) is recommended for patients with invasive distal bile duct IPNB. PD is a high complex procedure associated with the deterioration of endocrine and exocrine functions leading to a significant impact on quality of life. 2 Some authors have reported a new surgical approach leading to a complete resection of the common bile duct without pancreatectomy. 3 Methods We report the case of a 71-year-old female presented to our department with jaundice. At endoscopic ultrasound with cholangioscopy and CT scan, 2-cm distal bile duct mass tumor with villous component was seen. All needle biopsies were benign, and no distant disease was found. According to the risk of degeneration of this tumor, a surgical resection was decided. Results Intraoperative frozen section assessed the benignity of peripancreatic lymph nodes. We performed surgical ampullectomy with resection of the common bile duct. The intrapancreatic common bile duct was completely mobilized between the ampullectomy area and the upper edge of the pancreas. Frozen sections on distal and proximal margins of common bile duct were performed to discard malignancy. Finally, reconstruction consisted on the main pancreatic duct reimplantation to the duodenum and choledochoduodenostomy. The histological analysis confirmed the diagnosis of biliary papillomatosis with low-grade dysplasia. Conclusion This procedure allows complete resection of benign tumors with endobiliary extension and preserve intestinal continuity and pancreatic parenchyma.

ObjectiveIn alcoholic hepatitis (AH), development of targeted therapies is crucial and requires improved knowledge of cellular and molecular drivers in liver dysfunction. The unique opportunity of using explanted livers from patients with AH having undergone salvage liver transplantation allowed to perform more in-depth molecular translational studies.DesignWe studied liver explants from patients with AH submitted to salvage transplantation (n=16), from patients with alcoholic cirrhosis without AH (n=12) and fragments of normal livers (n=16). Hepatic cytokine content was quantified. Hepatocyte function and proliferation and the presence of hepatic progenitor cells (HPCs) were evaluated by immunohistochemistry, western blot or quantitative PCR. Mitochondrial morphology was evaluated by electron microscopy.ResultsLivers from patients with AH showed decreased cytokine levels involved in liver regeneration (tumour necrosis factor α and interleukin-6), as well as a virtual absence of markers of hepatocyte proliferation compared with alcoholic cirrhosis and normal livers. Electron microscopy revealed obvious mitochondrial abnormalities in AH hepatocytes. Importantly, livers from patients with AH showed substantial accumulation of HPCs that, unexpectedly, differentiate only into biliary cells. AH livers predominantly express laminin (extracellular matrix protein favouring cholangiocyte differentiation); consequently, HPC expansion is inefficient at yielding mature hepatocytes.ConclusionsAH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH.

BackgroundThe field of robotic liver resection (RLR) has developed in the past decades. This technique seems to improve the access to the posterosuperior (PS) segments. Evidence of a possible advantage over transthoracic laparoscopy (TTL) is not yet available. We aimed to compare RLR to TTL for tumors located in the PS segments of the liver in terms of feasibility, difficulty scoring, and outcome.MethodsThis retrospective study compared patients undergoing robotic liver resections and transthoracic laparoscopic resections of the PS segments between January 2016 and December 2022 in a high-volume HPB center. Patients’ characteristics, perioperative outcomes, and postoperative complications were evaluated.ResultsIn total, 30 RLR and 16 TTL were included. Only wedge resections were performed in the TTL group, while 43% of the patients in the RLR group had an anatomical resection (p < 0.001). The difficulty score according to the IWATE difficulty scoring system was significantly higher in the RLR group (p < 0.001). Total operative time was similar between the two groups. Complication rates, either overall or major, were comparable between the two techniques and hospital stay was significantly shorter in the RLR group. Patients in the TTL group were found to have more pulmonary complications (p = 0.01).ConclusionRLR may provide some advantages over TTL for the resection of tumors located in the PS segments.

BackgroundDespite improvement in colorectal liver metastasis (CLM) treatment, survival after liver surgery remains highly variable. Several clinicopathologic prognostic factors have been reported, but their validity in the era of more effective perioperative chemotherapy remains to be defined. The aim of this study is to analyze the prognostic factors associated with survival after CLM resection.MethodsClinicopathologic data of patients included in the MIROX phase III trial who underwent surgery for isolated CLMs were analyzed. The primary endpoints were 5-year overall survival (OS) and disease-free survival (DFS). Univariate Cox analysis was performed to identify associations with OS and DFS and select variables for inclusion in a multivariate model to determine their independent prognostic value.ResultsA total of 181 patients were analyzed. The median follow-up period was 6.42 years [95% confidence interval (CI) 5.15–8.71 years], and the 5-year OS and DFS rates were 67.1% and 35.4%, respectively. On multivariate analysis, Fong’s clinical risk score (CRS) as a categorical variable (CRS 0–1 vs. 2–3 vs. 4–5, p = 0.036) and polymorphonuclear neutrophil (PMN) count (> 6000/mm3 vs. ≤ 6000/mm3, p = 0.006) before chemotherapy were found to be independent prognostic factors for OS. However, only Fong’s CRS remained significantly associated with DFS (p = 0.027). The final OS model was used to establish a nomogram that allows individual OS estimations at 1, 3, 5, and 10 years.ConclusionsFong’s CRS was independently associated with DFS and poor OS after CLM resection with FOLFOX-based chemotherapy regimen. It could be useful in daily practice and future trials to select patients more accurately.

Background Liver and lungs are the two most frequent sites of metastatic spread of colorectal cancer (CRC). Complete resection of liver and/or lung metastases is the only chance of cure, and several studies have reported an improved survival after an aggressive treatment. Nevertheless, CRC liver metastases (CLM) have been recognized as a pejorative factor for patients undergoing pulmonary metastasectomy. We report our experience with patients successively operated on for CRC hepatic and pulmonary metastasis (CPM) and seek to identify prognostic factors. Methods All consecutive patients who had resection of CPM and CLM between 2001 and 2014 were enrolled in the study. Clinicopathological and survival data were retrospectively analysed. Results Forty-six patients underwent resections of both CLM and CPM. Hepatic resection preceded pulmonary resection in most cases (91.3%). The median intervals between the resection of the primary tumour and the hepatic recurrence and between hepatic and pulmonary recurrences were 12 months [0–72] and 21.5 months [1–84], respectively. The mortality rate following CPM resection was 4.3%. After a median follow-up of 41.5 months [0–126], 35 patients recurred of whom 14 (40%) and 11(31.4%) could benefit from repeated resection of recurrent CLM and CPM, respectively. The median and 5-year overall survivals (OS) were 53 months and 49%, respectively. No prognostic factor was identified. Conclusion An aggressive management of CLM and CPM, including repeated resections, may provide a long-term survival comparable to survival of patients with unique metastasectomy. The absence of prognostic factor may reflect the highly selected pattern of the eligible patients.

BackgroundChemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS).MethodsFrom 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (≥ 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (≤ 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues.ResultsAmong 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis ≥ 30% significantly compromised function, as well as NAS, especially grades 2–5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis ≥ 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS.ConclusionsIn this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction through steatosis or NAS.

BackgroundIt is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). MethodsPatients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. ResultsAmong 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups.ConclusionsPBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease‐free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT‐PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease‐free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease‐free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5‐Fluorouracil‐based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug‐resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities. Univariate and multivariate analysis show that CXCR2 and CXCL7 are independent factors of overall and disease‐free survivals. CXCR2 and CXCL7 expression are increased in metastatic liver tissue of colorectal adenocarcinoma treated with 5‐FU based neoadjuvant chemotherapy with or without bevacizumab.

BackgroundLaparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated.MethodsBetween 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis.ResultsAfter IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50–200] ml vs. 150 [IQR: 50–415] ml, p = 0.023) and shorter median hospital stay (5 [IQR: 4–7] days vs. 7 [6–9] days, p < 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 ± 19 after OLLS versus 13 ± 20 after LLLS, p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1–44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS, p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14], p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094–0.891], p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011).ConclusionThe laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel’s incision should be preferred to midline incision for specimen extraction after LLLS.

Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical and biological evaluation was performed every month. Radiological tumor response evaluation was realized every 3 months on the waiting list and every 6 months after LT. Among 327 patients listed for HCC, 62 (19%) were treated with Sorafenib. Sorafenib was initiated for HCC progression after loco-regional therapy (LRT) in 50% of cases and for impossibility of LRT in 50% of cases. The mean duration of treatment was 6 months. Thirty six patients (58%) dropped-out for tumor progression and 26 (42%) patients were transplanted. The 5-year overall and recurrent-free survival after LT was 77% and 48% respectively. Patients treated for impossibility of LRT had acceptable 5-year intention-to-treat overall and post-LT survivals. Conversely, patients treated for HCC progression presented high dropout rate and low intention-to-treat survival. Our results suggest that it is very questionable in terms of utility that patients treated for HCC progression should even be kept listed once the tumor progression has been observed.