Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) - a multicenter, randomized, controlled, open-label investigator-initiated trial.

BACKGROUND: Despite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy. METHODS/DESIGN: ACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material. DISCUSSION: ACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.

Initial clinical outcomes of robotic resection for perihilar cholangiocarcinoma: Is it safe and effective?

BACKGROUND AND OBJECTIVES: We aimed to describe our outcomes of robotic resection for perihilar cholangiocarcinoma, the largest single institutional series in the Western hemisphere to date. METHODS: Between 2016 and 2022, we prospectively followed all patients who underwent robotic resection for perihilar cholangiocarcinoma. RESULTS: In total, 23 patients underwent robotic resection for perihilar cholangiocarcinoma, 18 receiving concomitant hepatectomy. The median age was 73 years. Operative time was 470 min with an estimated blood loss of 150 mL. No intraoperative conversions to open or other intraoperative complications occurred. Median length of stay was 5 days. Four postoperative complications occurred. Three readmissions occurred within 30 days with one 90-day mortality. R0 resection was achieved in 87% of patients and R1 in 13% of patients. At a median follow-up of 27 months, 15 patients were alive without evidence of disease, two patients with local recurrence at 1 year, and six were deceased. CONCLUSIONS: Utilization of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with excellent perioperative outcomes. Further studies are needed to determine the long-term oncological outcomes.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Survival analysis of laparoscopic surgery and open surgery for hilar cholangiocarcinoma: a retrospective cohort study.

BACKGROUND/PURPOSE: This study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors. METHODS: The study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups. RESULTS: After screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150-0.940, P = 0.036; HR = 0.080, 95% CI = 0.010-0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150-0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130-6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170-22.960, P = 0.030). CONCLUSIONS: Compared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (<65 years), radical resection, and postoperative adjuvant therapy reduce the risk of death, and preoperative biliary drainage increases the risk of death.

[Surgical treatment and prognostic factors in perihilar tumors]. / Khirurgicheskoe lechenie i faktory prognoza pri perikhilyarnoi opukholi.

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors. MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery. RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024). CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

Value of palliative surgery in perihilar cholangiocarcinoma.

PURPOSE: The survival rate of patients with irresectable perihilar cholangiocarcinoma is remarkably poor. An essential part of palliation is treatment of obstructive cholestasis caused by the tumor. Currently, this is mainly performed endoscopically by stent or via PTBD, requiring frequent changes of the stents and limiting health-related quality of life due to the multiple hospital stays needed. The aim of this study was to evaluate surgical palliation via extrahepatic bile duct resection as an option for palliative treatment. METHODS: Between 2005 and 2016, we treated 120 pCCC patients with primary palliative care. Three treatment strategies were retrospectively considered: extrahepatic bile duct resection (EBR), exploratory laparotomy (EL), and primary palliative (PP) therapy. RESULTS: The EBR group required significantly less stenting postoperatively, and the overall morbidity was 29.4% (EBR). After the surgical procedure, fewer subsequent endoscopic treatments for stenting or PTBD were necessary in the EBR group over time. The 30-day mortality was 5.9% (EBR) and 3.4% (EL). The median overall survival averaged 570 (EBR), 392 (EL), and 247 (PP) days. CONCLUSIONS: In selected pCCC patients, palliative extrahepatic bile duct resection is a feasible option for treatment of obstructive cholestasis and should be reconsidered as a therapy option for these patients even in a palliative setting.

Pathogen detection in patients with perihilar cholangiocarcinoma: Implications for targeted perioperative antibiotic therapy.

BACKGROUND: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver. Therefore, targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma (pCCC). METHODS: Between December 1999 and December 2017, 251 pCCC patients were treated in our center. In total, 115 patients underwent a microbiological analysis. In addition to the characterization of the specific microorganisms and antibiotic resistance, we analyzed subgroups according to preoperative intervention. RESULTS: Enterococci (87/254, 34%) and Enterobacteria (65/254, 26%) were the most frequently detected genera. In 43% (50/115) of patients, Enterococcus faecalis was found in the bile duct sample. Enterococcus faecium (29/115) and Escherichia coli (29/115) were detected in 25% of patients. In patients with percutaneous transhepatic biliary drainage (3/8, 38%) or stents (24/79, 30%), Enterococcus faecium was diagnosed most frequently (P < 0.05). Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012 (P < 0.05). With regard to fungal colonization, the focus was on various Candida strains, but these strains generally lacked resistance. CONCLUSIONS: pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention. Specifically, targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection. In our cohort, the combination of meropenem and vancomycin represents an effective perioperative medical approach.

Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. METHODS: Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. RESULTS: Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. CONCLUSION: It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.

[Endoscopic treatment of obstructive jaundice in patients with Klatskin tumor]. / Endoskopicheskoe lechenie patsientov s mekhanicheskoi zheltukhoi pri opukholi Klatskina.

OBJECTIVE: To improve treatment outcomes in patients with Klatskin tumor and obstructive jaundice by using of endoscopic bilioduodenal stenting. MATERIAL AND METHODS: There were 1904 transpapillary interventions between August 2017 and February 2022. Endoscopic bilioduodenal stenting was performed in 250 patients including 25 (10%) ones with Klatskin tumor. RESULTS: Bilioduodenal plastic and self-expanding stents were installed in 19 (76%) and 6 (24%) patients, respectively. In Klatskin tumor type I, 11 patients (44%) underwent bilioduodenal stenting of common hepatic duct with plastic stent; 5 (20%) patients with Klatskin tumor type II received self-expanding stents. In case of tumor type IIIA, 3 (12%) patients underwent stenting of the right lobar duct with plastic stent. Four (16%) patients with Klatskin tumor type III B underwent stenting of the left lobar duct. Two 2 (8%) patients with Klatskin tumor type IV underwent bilateral bilioduodenal stenting with plastic and bifurcation self-expanding stents. Peroral cholangioscopy using the SpyGlass DS system was performed in 4 (16%) patients. No intraoperative complications were identified. One (4%) patient developed gastrointestinal bleeding in 2 postoperative days after retrograde intervention that did not require surgery. Moreover, 1 (4%) patient with distal dislocation of plastic bilioduodenal stent required redo bilioduodenal stenting. Three (12%) patients died from multiple organ failure despite adequate biliary decompression, and 22 (88%) patients were discharged in 8±5 days after retrograde intervention. CONCLUSION: Bilioduodenal stenting as minimally invasive and physiological method was highly effective for obstructive jaundice in patients with Klatskin tumor. Peroral cholangioscopy using the SpyGlass system provides effective and safe direct visualization of the biliary tract, as well as biopsy for morphological verification and prescription of chemotherapy in patients with intraductal growth of tumor.

Endoscopic sphincterotomy and endoscopic biliary stenting do not affect the sensitivity of transpapillary forceps biopsy for the diagnosis of bile duct adenocarcinoma.

BACKGROUND: The pathological evaluation of tissues with cholangitis is considered difficult, which can often occur after endoscopic sphincterotomy (EST) and endoscopic biliary stenting (EBS). This study aimed to evaluate the influence of a history of EST and EBS on the sensitivity of transpapillary forceps bile duct biopsy (TB) for bile duct adenocarcinoma. METHODS: This retrospective study included consecutive cases of bile duct adenocarcinoma in which TB was performed before July 2020 until the number exceeded that required to support statistical and noninferiority analyses of the sensitivity of TB between patients with and without each variable. The incidence of postprocedural adverse events related to each factor was also investigated. RESULTS: Overall, 280 samples were required in each group, and 437 subjects (792 samples) were included. The sensitivity of TB was 63.6% for the subjects and 59.6% for the biopsy samples. For the biopsy samples, the sensitivity did not differ significantly between samples from patients with and without a history of EST (59.1% vs. 58.9%, P = 0.952) and EBS (62.1% vs. 55.4%, P = 0.065). The sensitivity was significantly higher for samples from patients with jaundice (67.9% vs. 57.0%, P = 0.008). There were significantly fewer procedure-related adverse events in patients with a history of EST (10.8% vs. 19.0%, P = 0.017) and EBS (12.0% vs. 21.7%, P = 0.005). CONCLUSIONS: A history of EST or EBS did not influence sensitivity of TB but significantly decreased the incidence of adverse events. To safely and reliably perform TB to diagnose bile duct adenocarcinoma, planning, including for EST and EBS, is necessary.

Effects of portal vein resection and hepatic artery resection on long-term survival in Klatskin tumor: a meta-analysis.

BACKGROUND: Surgical treatment is currently the only way to achieve the clinical cure for Klatskin tumor. However, whether combined vascular resection should be combined during surgeries is still controversial. The aim of this article was to analyze the effect of portal vein resection (PVR) and hepatic artery resection (HAR) on the long-term survival after surgery for Klatskin tumor. METHODS: Articles about Klatskin tumor with PVR and HAR, which were published from 2000 to 2020, were searched using PubMed, Embase, and EBSCO. HR with a 95% CI of overall survival, recurrence-free survival, disease-free survival, 3- and 5-year survival rate, and median survival time were reported to evaluate prognosis. RESULTS: A total of 17 articles were included. The total case number of these studies was 3150 (685 in the PVR group, 345 in the HAR group, and 2120 in the control group). Survival analyses showed that both vascular resection types were poor prognostic factors (PVR: HR = 1.50, 95% CI = 1.24-1.81, P < 0.001; HAR: HR = 1.68, 95% CI = 1.26-2.24, P < 0.001; the pooled effect size of the two groups: HR = 1.55, 95% CI = 1.32-1.82, P < 0.001). In general, the analyses of 3- and 5-year survival and median survival time showed that both vascular resection types tended to be poor prognostic factors, but most of recent researches showed that the PVR did not lead to a poor prognosis. CONCLUSION: PVR should be used when necessary to achieve R0 resection of Klatskin tumor and improve the long-term survival of patients. Whether HAR should be performed or not is still need to be evaluated.

Endoscopic management of perihilar cholangiocarcinoma.

Endoscopic management for perihilar cholangiocarcinoma (PHCC) is evolving toward more accurate diagnosis and safer drainage. In imaging, it is important to diagnose the entire lesion using multidetector-row computed tomography to determine resectability and optimal surgical planning, followed by local diagnosis using endoscopic retrograde cholangiopancreatography. Video peroral cholangioscopy and probe-based confocal laser endomicroscopy have been newly introduced as diagnostic imaging methods and are being applied clinically. In transpapillary forceps biopsy for PHCC diagnosis, the location in the bile duct (for mapping biopsy) and the number of biopsy samples should be determined depending on resectability, the morphological type, and future surgical planning. Preoperative drainage has shifted from percutaneous transhepatic biliary drainage to endoscopic nasobiliary drainage given the possibility of seeding metastasis. In addition, considering potential patient discomfort from a nasal tube, the usefulness of the placement of a plastic stent above the papilla (inside stent) as a bridging therapy for surgery has been reported. For drainage of unresectable PHCC, the improved prognosis due to advances in chemotherapy has necessitated a strategy that accounts for reintervention. Thus, in addition to uncovered self-expandable metallic stents (SEMS), exchangeable slim fully covered SEMS and inside stents have started to be used. In addition to the conventional transpapillary approach, an endoscopic ultrasonography-guided approach has been introduced, and a combination of both methods has also been proposed. To improve the quality of life and prognosis of PHCC patients, endoscopists need to understand and be able to use the various methods of endoscopic management for PHCC.

Klatskin Tumor: A Survival Analysis According to Tumor Characteristics and Inflammatory Ratios.

Background and Objectives: The aim was to evaluate the association of inflammatory biomarkers with resectability and overall survival in hilar cholangiocarcinoma. Materials and Methods: We conducted a retrospective cohort study over 72 consecutive surgical cases of Klatskin tumor over an 11-year period. The sample was divided into two groups: 42 surgical resection cases and 30 unresectable tumors. Values of inflammatory ratios were compared according to the resectability. Log-rank test, univariate, and multivariate Cox proportional hazards models were used to evaluate the overall survival. Results: Subjects were between 42−87 years old (average age of 64.91 ± 9.15 years). According to the procedure: 58.33% benefited from resection (with a 30.95% R0 resection rate) and 41.66% had palliative surgery. Elevated NLR (neutrophil to lymphocyte ratio), PLR (platelet to lymphocyte ratio), and SII (systemic immune-inflammation index), and lower LMR (lymphocyte to monocyte ratio) at admission were associated with unresectable tumors (p < 0.01). For the multivariate Cox proportional hazard models, increased absolute values of NLR, PLR, and SII were associated with lower survival; no differences were observed for LMR absolute value. The cut-off value of NLR ≥ 6 was associated with lower survival. The median survival time for all subjects was 442 days, with 774 days for the resection group and 147 days for the group with palliative surgery. Conclusions: In hilar cholangiocarcinoma, inflammatory ratios are associated with tumor resectability. Tumor excision conferred an important advantage in survival. Elevated NLR, PLR, and SII values at admission significantly increased the hazard ratio. LMR had no influence on survival.

Double rarity: malignant masquerade biliary stricture in a situs inversus totalis patient.

BACKGROUND: Situs inversus totalis is a rare anatomical variation of both the thoracic and the abdominal organs. Common bile duct strictures can be caused by malignant and benign diseases as well. 7-18% of the latter ones are 'malignant masquerade' cases, as pre-operative differentiation is difficult. CASE PRESENTATION: We present the case of a 68y male patient with known situs inversus totalis and a recent onset of obstructive jaundice caused by a malignant behaving common bile duct stricture. Technically difficult endoscopic retrograde cholangiopancreatography, brush cytology, magnetic resonance cholangiopancreatography, endoscopic ultrasound, and percutaneous transhepatic drainage with stent implantation were performed for proper diagnosis. Cholecystectomy, common bile duct resection with hilar lymphadenectomy, and hepatico-jejunostomy have been performed following multidisciplinary consultation. The final histology report did not confirm any clear malignancy, the patient is doing well. CONCLUSION: In situs inversus patients, both diagnostic and therapeutic procedures can lead to various difficulties. Benign biliary strictures are frequently misdiagnosed preoperatively as cholangiocellular carcinoma. Surgery is usually unavoidable, involving a significant risk of complications. The co-existence of these two difficult diagnostic and therapeutic features made our case challenging.

Stage I-laparoscopy partial ALPPS procedure for perihilar cholangiocarcinoma.

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.

There Is a Great Future in Plastics: Personalized Approach to the Management of Hilar Cholangiocarcinoma Using a 3-D-Printed Liver Model.

In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and doctor-patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing enbloc the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.

The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis.

BACKGROUND: The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. METHODS: All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. RESULTS: Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. CONCLUSION: Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.

Placement of a newly designed partially covered T- or Y-configured self-expanding metallic stent for hilar biliary obstruction: technical note.

PURPOSE: To investigate the technical success, efficacy, and safety of a newly designed partially covered bilateral self-expanding metallic stent (SEMS) in patients with malignant biliary obstruction. MATERIAL AND METHODS: From May 2016 to November 2017, ten patients with malignant hilar biliary stenosis (bismuth type II-IV) underwent stent placement with the newly designed partially covered T/Y-configured SEMS. Technical success, drainage catheter removal, jaundice remission, early and late complications, stent patency, and overall survival were analyzed. RESULTS: The stent was successfully deployed in all patients. The total bilirubin level significantly decreased one month after stent placement (P < 0.05). Drainage catheter removal rate was 90%. Two cases (20%) experienced early complications (bile duct hemorrhage and cholangitis) and two cases (20%) experienced late complications (hepatic abscess and cholangitis). During the follow-up (mean 276 days; range 57-503 days) stent occlusion occurred in three patients (30%), and two patents died of hepatic failure. The median stent patency and overall survival were 275 days (95% CI 223.8-326.3 days) and 428.9 days (95% CI 347.9-509.8 days), respectively. CONCLUSION: The newly designed partially covered T/Y-configured SEMS is technically feasible and clinically effective for biliary trifurcation obstruction.

Endoscopic Versus Percutaneous Preoperative Biliary Drainage in Patients With Klatskin Tumor Undergoing Curative Surgery: A Systematic Review and Meta-Analysis of Short-Term and Long-Term Outcomes.

Aims. To compare short-term and long-term outcomes of preoperative endoscopic biliary drainage (EBD) and percutaneous biliary drainage (PBD) in patients with Klatskin tumor undergoing curative surgery. Methods. We conducted a search of electronic information sources to identify all studies comparing EBD and PBD in patients with Klatskin tumor undergoing curative surgery. We used the Newcastle-Ottawa Scale to assess the risk of bias observational studies. Random-effects or fixed-effects modeling was applied as appropriate to calculate pooled outcome data. Results. We identified 9 observational studies, enrolling a total of 1436 patients. The patients in the PBD group had more advanced disease than those in EBD group in terms of Bismuth-Corlette classification and tumor classification. EBD was associated with higher risks of postprocedural complications (odds ratio [OR] =2.24, P = .001), conversion to another drainage method (OR =11.16, P < .00001), cholangitis (OR = 4.58, P < .0001), and pancreatitis (OR = 8.90, P = .009) than PBD; there was no difference between the 2 methods in terms of technical success (OR = 0.79, P = .50) and tube dislocation (OR = 0.81, P = .54). Regarding the postoperative outcomes, there was no difference in terms of 30-day mortality (OR = 0.61, P = .16) and major postoperative complications (OR = 0.60, P = .06). Regarding the long-term outcomes, EBD was associated with lower risks of seeding metastasis (OR = 0.46, P = .0004) and 5-year recurrence (OR = 0.72, P = .010), and better 5-year survival (OR = 1.62, P = .001). Conclusions. EBD may be associated with higher procedure-related complications compared with PBD as a preoperative biliary drainage method in patients with Klatskin tumor undergoing curative surgery. The available evidence on long-term oncological and survival outcomes are subject to confounding by indication, and high-quality randomized controlled trials are required for definite conclusions.

Surgery for cholangiocarcinoma.

Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5-year overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post-operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection.