CT Texture Analysis of Perihilar Cholangiocarcinoma-Associations With Tumor Grading, Tumor Markers and Clinical Outcome.

BACKGROUND: Texture analysis derived from computed tomography (CT) may provide clinically relevant imaging biomarkers associated with tumor histopathology. Perihilar cholangiocarcinoma is a malignant disease with an overall poor prognosis. AIMS: The present study sought to elucidate possible associations between texture features derived from CT images with grading, tumor markers, and survival in extrahepatic, perihilar cholangiocarcinomas tumors. METHODS: This retrospective study included 22 patients (10 females, 45%) with a mean age of 71.8 ± 8.7 years. Texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. Survival and clinical parameters were used as primary study outcomes. RESULTS: In discrimination analysis, "S(1,1)SumVarnc" was statistically significantly different between patients with long-term survival and nonlong-term survival (mean 275.8 ± 32.6 vs. 239.7 ± 26.0, p = 0.01). The first-order parameter "skewness" was associated with the tumor marker "carcinoembryonic antigen" (CEA) (r = -0.7, p = 0.01). A statistically significant correlation of the texture parameter "S(5,0)SumVarnc" with tumor grading was identified (r = -0.6, p < 0.01). Several other texture features correlated with tumor markers CA-19-9 and AFP, as well as with T and N stage of tumors. CONCLUSION: Several texture features derived from CT images were associated with tumor characteristics and survival in patients with perihilar cholangiocarcinomas. CT texture features could be used as valuable novel imaging markers in clinical routine.

Prognostic impact of liver resection side in peri-hilar cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a highly lethal hepatobiliary cancer. Radical resection offers the best chance for extended survival, but the efficacy of left-sided hepatectomy (LH) versus right-sided hepatectomy (RH) remains controversial. METHODS: A systematic review and meta-analysis of non-randomized cohort studies comparing LH and RH in patients with resectable pCCA was conducted. Subanalyses were performed based on year of publication, region, number of cases and Bismuth classification (BC) ≥ III. RESULTS: Nineteen studies involving 3838 patients were included, with 1779 (46 %) undergoing LH and 2059 (54 %) undergoing RH. LH was associated with increased overall survival (OS) in subgroup analysis of studies reporting hazard ratios (HR) (logHR 0.59; p = 0.04). LH showed higher rates of arterial resection (14 % vs. 1 %), transfusion (51 % vs. 41 %), operation time (MD 31.44 min), and bile leakage (21 % vs. 18 %), but lower rates of post-hepatectomy liver failure (9 % vs. 21 %) and 90-day mortality (8 % vs 16 %). Three-year disease-free survival rates increased in Western centers but decreased in Eastern centers. CONCLUSION: LH is linked to higher OS in this analysis but is a more demanding technique. Resection side decision should consider several factors, including future liver remnant, tumor location, vascular involvement, and surgical expertise.

Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center.

BACKGROUND: The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy. METHODS: A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb. RESULTS: Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190-450), and the median estimated blood loss was 360 mL (range, 260-1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3-43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years. CONCLUSION: Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Right hepatectomy compared with left hepatectomy for resectable Klatskin tumor: A systematic review across tumor types.

BACKGROUND: The prognosis of Klatskin tumors is poor, and radical surgery with disease-free surgical margins (R0) represents the treatment capable of ensuring the best long-term outcomes. In patients with Klatskin tumors, both right hepatectomy and left hepatectomy might achieve R0 surgical margins. This systematic review concentrated on a comparative investigation between left hepatectomy and right hepatectomy, aiming to furnish clinical evidence and to aid in surgical decision-making for Klatskin tumor depending on its spread within the bile duct tree. METHODS: The eligible articles in the study were obtained from PubMed, Medline, and Scopus databases, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis, and they were categorized according to the type of Klatskin tumor treated with right hepatectomy or left hepatectomy. The studies that analyzed the outcomes related to the 2 surgical techniques without focusing on the type of Klatskin tumor were included in a separate paragraph and table. RESULTS: In total, 21 studies were included. Four studies reported outcomes of right hepatectomy or left hepatectomy for Klatskin type I/II tumor, 2 for Klatskin type II/IV tumor, 2 for Klatskin type III tumor, and 2 for Klatskin type IV. Eleven studies included the outcomes of right hepatectomy and left hepatectomy for hilar cholangiocarcinoma without specifying the type of Klatskin tumor. Although long-term oncologic outcomes seem comparable between right hepatectomy and left hepatectomy when achieving R0 resection for Klatskin type III/IV tumors, there may exist a marginal oncologic edge and reduced complication rates favoring left hepatectomy in individuals with Klatskin type I/II tumors. DISCUSSION: Right hepatectomy traditionally has played a central role in treating Klatskin tumor, but recent studies have questioned its oncologic efficacy and surgical risks. Currently, there is a lack of evidence regarding the ideal surgical approach for each type of Klatskin tumor, and surgical strategy relies heavily on the individual surgeon's experience and technical skills. The management of Klatskin tumors necessitates specialized hepatobiliary surgical centers capable of conducting major hepatectomy with thorough lymphadenectomy, biliary, and vascular reconstructions. There is a need for studies with larger sample sizes to achieve a wide consensus about the superiority of one surgical technique over the other in cases in which both right hepatectomy and left hepatectomy can achieve an R0 margin.

Preventing futile surgery in Intrahepatic and Perihilar cholangiocarcinomas: Can we identify preoperative factors to improve patient selection and optimize outcomes?

BACKGROUND: Intraoperative unresectability, postoperative deaths and early recurrences remain devastating futile events in the surgical management of Intrahepatic cholangiocarcinomas (iCCA) and Perihilar cholangiocarcinomas (pCCA). The present study aims to determine the preoperative predictors of futile surgery in cholangiocarcinomas. METHODS: Consecutive hepatectomies for iCCA and pCCA, between September 2010 and June 2022 were included. Futility of surgery was defined as either intraoperative unresectability, postoperative 30-day mortality or recurrence within six months of surgery. Multivariable logistic regression was used to identify predictors of futility. RESULTS: One hundred and fifty patients of iCCA and pCCA underwent surgery during the time period. Thirty-seven (38.1 %) out of 97 patients of iCCA and 25(47.16 %) out of 53 patients of pCCA underwent futile resection. The predictive factors of futile surgery for iCCA were tumour number (≥2) (OR, 9.705; 95%CI, 2.378-39.614; p = 0.002), serum aspartate transaminase (OR, 8.31; 95%CI, 2.796-24.703; p < 0.001) and serum CA-19.9 (>37 U/ml) (OR, 2.95; 95%CI, 1.051-8.283; p = 0.04). The predictive factors of futility for pCCA were lymph node involvement (OR, 7.636; 95%CI, 1.824-31.979; p = 0.005) and serum alkaline phosphatase (>562.5 U/L) (OR, 11.211; 95%CI, 1.752-71.750; p = 0.011). CONCLUSION: Futile surgery was observed in over one third of our patients. Five strong preoperative predictors of futility were identified. Careful analysis of these factors may reduce futile surgical explorations.

Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

Comparative study of short-and long-term results in patients with perihilar cholangiocarcinoma undergoing surgical resection: does the extent and side of resection really affect outcome?

BACKGROUND: The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. METHODS: A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. RESULTS: Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. CONCLUSIONS: In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.

Clinical features and prediction of long-term survival after surgery for perihilar cholangiocarcinoma.

INTRODUCTION: The treatment of perihilar Cholangiocarcinoma (pCCA) poses specific challenges not only due to its high perioperative complication rates but also due its dismal long-term prognosis with only a few long-term survivors (LTS) among the patients. Therefore, in this analysis characteristics and predictors of LTS in pCCA patients are investigated. MATERIAL AND METHODS: In this single center analysis, patients undergoing curative-intent liver resection for pCCA between 2010 and 2022 were categorized into long-term and short-term survivors (STS) excluding perioperative mortality. Binary logistic regression was used to determine key differences between the groups and to develop a prognostic composite variable. This composite variable was subsequently tested in the whole cohort of surgically treated pCCA patients using Cox Regression analysis for cancer-specific survival (CSS). RESULTS: Within a cohort of 209 individuals, 27 patients were identified as LTS (median CSS = 125 months) and 55 patients as STS (median CSS = 16 months). Multivariable analysis identified preoperative portal vein infiltration (OR = 5.85, p = 0.018) and intraoperative packed red blood cell (PRBC) transfusions (OR = 10.29, p = 0.002) as key differences between the groups. A prognostic composite variable based on these two features was created and transferred into a Cox regression model of the whole cohort. Here, the composite variable (HR = 0.35, p<0.001), lymph node metastases (HR = 2.15, p = 0.001) and postoperative complications (HR = 3.06, p<0.001) were identified as independent predictors of CSS. CONCLUSION: Long-term survival after surgery for pCCA is possible and is strongly negatively associated with preoperative portal vein infiltration and intraoperative PRBC transfusion. As these variables are part of preoperative staging or can be modulated by intraoperative technique, the proposed prognostic composite variable can easily be transferred into clinical management to predict the oncological outcome of patients undergoing surgery for pCCA.

Partial liver resection alters the bile salt-FGF19 axis in patients with perihilar cholangiocarcinoma: Implications for liver regeneration.

BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.

A single institution's experience with robotic resections of biliary tract cancers: an analysis of the short-term outcomes and long-term survival.

INTRODUCTION: Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma (IHCC), and gall bladder cancer are difficult malignancies to treat and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. Although minimally invasive approaches show promise, data remain limited. METHODS: With the institutional review board's approval, we prospectively followed 100 patients between 2013 and 2023 who underwent robotic surgical resection for perihilar, IHCC, and gallbladder cholangiocarcinoma. Data are presented as median (mean ± SD). Significance was accepted at P ≤ .05. RESULTS: The median patient age was 70 years, and the median operative duration was 333 min, with an estimated blood loss of 200 mL. Importantly, no unplanned conversions occurred, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There were a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were 3 in-hospital mortalities and 5 90-day mortalities. R0 resection was achieved in 87% of patients and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, whereas 6% continued to live with the disease, and 32% did not survive. CONCLUSION: Our experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncologic outcomes.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Textbook oncologic outcomes among patients undergoing laparoscopic, robotic and open surgery for intrahepatic and perihilar cholangiocarcinoma.

BACKGROUND: Textbook oncologic outcome (TOO) serves as a composite, oncologic metric for surgical quality of care. We sought to evaluate variations in TOO among patients undergoing laparoscopic, robotic, and open surgery for intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. METHODS: Patients who underwent liver resection for iCCA and pCCA between 2010 and 2018 were identified from the National Cancer Database. Entropy balancing was performed for covariate balancing and multivariable regression was used to evaluate the association between surgical approach and TOO. RESULTS: Among 5434 patients who underwent hepatic resection between 2010 and 2018, 3888 (71.6%) had iCCA, and 1546 (28.4%) had pCCA. TOO was achieved in 11.7% (n = 454), and 18.8% (n = 291) of patients with iCCA and pCCA, respectively. There was a difference in achievement of TOO relative to operative approach among patients with iCCA (robotic: 6.2% vs. laparoscopic: 8.1% vs. open: 12.5%; p = 0.002). After entropy balancing, patients with iCCA undergoing laparoscopic surgery had 32% reduced odds of achieving TOO (Ref: open surgery; laparoscopic, OR 0.68, 95%CI 0.49-0.93; p = 0.016; robotic, OR 0.69, 95%CI 0.34-1.39; p = 0.298). CONCLUSIONS: Usage of composite oncologic measures such as TOO may allow for a holistic assessment of different approaches to hepatic resection among patients with CCA.

Total Laparoscopic Radical Resection of S1 + S4 for Bismuth-Corlette Type IV Hilar Cholangiocarcinoma (With Video).

BACKGROUND: The management of Bismuth-Corlette type IV hilar cholangiocarcinoma typically necessitates extensive hepatectomy, resection of the extrahepatic bile ducts, regional lymph node dissection, and reconstruction of the biliary tract; however, there is a high incidence of postoperative liver dysfunction and failure. METHODS: A 64-year-old male patient was admitted to our department after 1 month of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was 334 µmol/L and his direct bilirubin was 221 µmol/L. His carbohydrate antigen 19-9 was > 1200.00 U/mL, his carcinoembryonic antigen was 98.90 U/mL, and his α-fetoprotein was normal. Enhanced computed tomography (CT) and magnetic resonance imaging scans revealed a thickened and enlarged biliary tree extending from the common hepatic duct to the orifices of the left and right hepatic ducts. RESULTS: The patient underwent total laparoscopic radical resection of S1 + S4, accompanied by radical lymphadenectomy with skeletonization and biliary reconstruction. The surgery was successfully conducted within 450 min, with a minimal blood loss of 200 mL. The histological grading was T2bN1M0 (stage III). CT on postoperative day 5 showed satisfactory postoperative recovery. The patient was discharged from the hospital on postoperative day 10 without complications, following which the patient underwent a regimen of single-agent capecitabine chemotherapy. Over a 20-month follow-up period, no recurrence was observed. CONCLUSIONS: Resection of hepatic segments S1 + S4 is a viable surgical option for hilar carcinoma in cases with poor liver function or when the carcinoma is confined to both hepatic ducts without invasion of the hepatic artery and portal vein.

Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a single-center propensity score matching analysis.

Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation's success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People's Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50-500) vs 310 (100-850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.