Pancreaticoduodenectomy for distal cholangiocarcinoma at a South African centre.

BACKGROUND: Surgical resection of distal cholangiocarcinoma (dCCA) offers the only chance for cure and long-term survival. The current literature provides limited data regarding the surgical management and long-term outcomes of dCCA. This study aims to describe the presentation, management, and outcomes of dCCA at a large academic referral centre in South Africa. METHODS: A retrospective study was performed of all patients who underwent curative-intended surgery for dCCA at Groote Schuur Hospital from 2000 to 2020. RESULTS: Over 21 years, 25 patients underwent pancreaticoduodenectomy (PD) for dCCA. Most patients were male (68%), and the mean age was 56.8 years. Of the patients, 22 (84%) underwent preoperative biliary drainage (PBD). There were 29 recorded complications in 25 patients; postoperative pancreatic fistula (POPF) and surgical site infection (SSI) each occurred in 24% of the cohort. The mean hospital stay was 17.2 days without perioperative mortality. With none lost to follow-up, the 1, 3, 5, 10, and 20-year survival rates were 84%, 24%, 16%, 12%, and 4%, respectively. Only T3 status was associated with significantly lower overall survival (OS). Age, albumin levels, PBD, margin status (R0 vs. R1), and nodal status (N0 vs. N1/N2) did not influence OS. CONCLUSION: This is the first study detailing the management and outcomes of dCCA from sub-Saharan Africa (SSA). Despite the complete resection of dCCA, the prognosis is poor, and the long-term survival rate in our study is equivalent to that reported in the literature. T3 disease is an important prognostic factor and is associated with poor OS. Surprisingly, nodal disease and margin status did not affect OS in the cohort of patients.

Real-world outcomes of chemotherapy plus immune checkpoint inhibitors versus chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma.

Background: There are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients. Methods: Patients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety. Results: 81 eligible patients were included in the study (chemotherapy plus anti-PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30-0.94, P = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27-0.87); P = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3-4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable. Conclusion: Chemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone.

Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported. METHODS: Immunohistochemistry (IHC) with anti-DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (-, 1+, 2+, 3+) and divided into two groups (DGKα- and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki-67 expression was evaluated as a cell proliferation marker. The number of Ki-67-positive cells was counted, and the relationship with DGKα expression was examined. RESULTS: DGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα- group (-: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence-free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki-67-positive cells increased in association with the staining levels of DGKα. CONCLUSION: Pathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.

Efficacy and safety of lenvatinib plus durvalumab combined with hepatic arterial infusion chemotherapy for unresectable intrahepatic cholangiocarcinoma.

Background: The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC. Materials and methods: Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs). Results: A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs. Conclusion: Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy.

Background: Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments. Methods: The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn. Results: Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS. Conclusion: In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.

Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

An assessment of risk factors for recurrence and survival for patients undergoing liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with increasing rates of incidence and mortality. Surgical resection is curative for patients who are diagnosed at early stages of iCCA. Limited data exist regarding risk factors for postresection recurrence and overall survival as iCCA is rare, and majority of patients are diagnosed at an advanced stage and thus not candidates for resection. We aimed to analyze clinical and laboratory characteristics, tumor histology, locoregional invasion, recurrence and survival in patients undergoing curative resection for iCCA. METHODS: All patients who underwent curative resection for iCCA between 2006 and 2023 at our institution were included in the study. Clinical characteristics, laboratory, histological and follow-up data were collected. RESULTS: The 1-, 3-, and, 5-year survival rates were 90.9%, 65.9% and 44.2%, respectively. About 65.6% of patients had recurrence in a median of 1.2 years after liver resection. Positive surgical margins were present in 20.73% of patients. Notably, 80.51% had solitary tumor and the remaining 19.48% had multifocal tumor. A total of 64.51% of patients received adjuvant chemotherapy after resection. A total of 26 (31.3%) patients had died during the follow-up period. Duration from liver resection to last follow-up or death was 1.6 years (0.8-3.2). Overall median survival was 4.6 years. The presence of lymph node metastases, vascular invasion, positive surgical margin and advanced tumor stage at diagnosis were associated with significantly worse overall survival, which remained significant in multivariable model for advanced tumor stage and positive surgical margin. CONCLUSION: Despite curative resection, recurrence rate is high and overall survival is poor in patients with iCCA. Real-world data regarding patient characteristics and longitudinal follow-up remain important as iCCA is a rare malignancy.

Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment.

BACKGROUND: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. METHODS: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4-CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. RESULTS: The percentages of patients in none CTC, OCT4-CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4-CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4-CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. CONCLUSION: OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas.

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.

Is routine lymph node dissection recommended for liver resection of intrahepatic cholangiocarcinoma? A systematic review and meta-analysis.

BACKGROUND/PURPOSE: This meta-analysis aimed to elucidate the therapeutic effects of routine lymph node dissection (LND) with liver resection on intrahepatic cholangiocarcinoma (ICC). METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing LND and non-LND for ICC liver resection. The primary outcome was overall survival (OS), and secondary outcomes were disease-free survival (DFS), in-hospital morbidity, blood loss, and R0 rate. RESULTS: Seventeen studies involving 4407 patients were included. The OS did not differ between the LND (n = 2158) and non-LND (n = 2249) groups (HR, 1.05; 95% CI, 0.83-1.32). The secondary outcomes did not differ significantly between the groups. Subgroup analyses stratified by the risk of bias showed a significant difference in OS between the high- and low-risk groups (P = 0.0008). In the low-risk group, LND (vs. non-LND) was associated with superior OS (HR, 0.76; 95% CI, 0.59-0.98). Most studies in low-risk groups involved patients who were clinically node-negative. CONCLUSIONS: The therapeutic effects of routine LND for ICC have not been demonstrated. However, LND had a positive impact on OS in studies with a low risk of bias, thus suggesting that there may be a subset of ICC patients who would benefit from LND.

Evolution of transplant oncology indications: a single-institution experience over 40 years.

Liver transplantation (LT) for uncommon tumoral indications has changed across the decades, with impaired results reported in the first historical series mainly for non-tumoral-related causes. Recently, renewed interest in liver transplant oncology has been reported. The study aims to analyze a mono-center experience exploring the evolution and the impact on patient survival of LT in uncommon tumoral indications. A retrospective analysis of 851 LT performed during 1982-2023 was investigated. 33/851 (3.9%) uncommon tumoral indications were reported: hepatocellular carcinoma (HCC) on non-cirrhotic liver (n = 14), peri-hilar (phCCA) (n = 8) and intrahepatic cholangiocarcinoma (i-CCA) (n = 3), metastatic disease (n = 4), hepatic hemangioendothelioma (n = 2), and benign tumor (n = 2). Uncommon tumoral indications were mainly transplanted during the period 1982-1989, with a complete disappearance after the year 2000 and a slight rise in the last years. Poor outcomes were reported: 5-year survival rates were 28.6%, 25.0%, 0%, and 0% in the case of HCC on non-cirrhotic liver, phCCA, i-CCA, and metastases, respectively. However, the cause of patient death was often related to non-tumoral conditions. LT for uncommon oncological diseases has increased worldwide in recent decades. Historical series report poor survival outcomes despite more recent data showing promising results. Hence, the decision to transplant these patients should be under the risk and overall benefit of the patient. The results of the ongoing protocol studies are expected to confirm the validity of the unconventional tumor indications.

Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection.

BACKGROUND: Although many guidelines recommend performing lymph node dissection (LND) during surgery for intrahepatic cholangiocarcinoma (ICC), there is no evidence for patients with incidentally detected ICC who did not undergo LND. This study aimed to identify the role of LND in patients with incidental ICC. METHODS: The data from 284 patients who had undergone radical surgery for ICC from 2000 to 2020 were retrospectively reviewed. The enrolled patients were divided into 3 groups according to their T stage (T1 vs T2 vs T3 + 4). Moreover, the patients of each T group were divided into 3 groups according to their nodal status (N0 vs N1 vs Nx) and their survival outcomes were compared. RESULTS: Survival outcomes of Nx group were statistically similar to that of N0 group in T1 stage (Nx vs N0: disease-free survival [DFS] [months], 129.0 [75.6-182.4] vs 125.0 [65.7-184.3], P = .948; overall survival [OS] [months], 175.0 [153.9-196.1] vs 173.0 [109.0-237.0], P = .443). In contrast, survival outcomes of Nx group in the other T stage (T2 and T3 + 4) were poorer than that of N0 group and were better than that of N1 group. In addition, in the Nx subgroup analysis according to T stage, T1 group showed significantly better survival outcomes than the other groups (T1 vs T2 vs T3 + 4: DFS [months], 129.0 [75.9-182.1] vs 16.0 [9.8-22.2] vs 13.0 [0.3-25.7], P < .001; OS [months], 175.0 [153.9-196.1] vs 53.0 [30.8-75.2] vs 37.0 [17.6-56.4], P < .001). CONCLUSION: Patients with ICC incidentally diagnosed as having T2 or above T stage may consider additional LND.

Predicting prognosis in intrahepatic cholangiocarcinoma by the histopathological features.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS: Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS: A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION: High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. METHODS: We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. RESULTS: The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. CONCLUSIONS: Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

The Integrated Prediction of Clinical and Pathological Factors on the Prognosis of Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The primary objective was to construct a high-performing prognostic risk model to accurately forecast the prognosis of patients diagnosed with intrahepatic cholangiocarcinoma (iCCA). METHODS: We retrospectively collected clinical data from the MSK database on 125 patients diagnosed with iCCA. Random sampling was utilized to divide patients into a training set and a validation set, maintaining a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were utilized to identify independent prognostic factors influencing OS. Based on these independent factors, a model nomogram was established. The performance of the prognostic prediction models was assessed through calibration curves and C-index calculations. The Kaplan-Meier method was used to plot survival curves. Time-dependent ROC curve was used to evaluate the accuracy of the model. RESULTS: A nomogram was developed, incorporating hepatitis C, CA19, tumor extent, tumor size, LVI, positive lymph nodes, and TMB as predictive factors. The C-index for the training set was .78 and the validation set was .68. Using the riskscore derived from the nomogram, patients were stratified into high- and low-risk groups. The high-risk group exhibited considerably lower OS and RFS compared to the low-risk group in the training set (P < .05). However, no significant difference was detected in RFS among different risk groups in the validation set (P > .05). The AUC for 1-year, 3-year, and 5-year survival was .89, .69, and .69, respectively. CONCLUSION: We successfully developed and validated a prognostic nomogram for iCCA, demonstrating its excellent accuracy in predicting patient outcomes and providing clinicians with a potential prognostic tool.

Long-term oncological results of percutaneous radiofrequency ablation for intrahepatic cholangiocarcinoma.

INTRODUCTION: The effectiveness of percutaneous radiofrequency ablation (RFA) in intrahepatic cholangiocarcinomas (iCCA) remains insufficiently studied. METHODS: We conducted a retrospective study including patients with histologically proven iCCA within Milan criteria treated by percutaneous RFA from 2000 to 2022. The primary outcome was overall survival in treatment-naive patients and secondary outcomes included ablation completeness, adverse events, local and distant recurrence. A total of 494 patients with hepatocellular carcinoma (HCC) on cirrhosis treated by RFA were included as a comparison group. Oncological events were analysed using Kaplan-Meier, log-rank and univariate/multivariate Cox models. RESULTS: The main population included 71 patients, mostly cirrhotic (80%) with solitary tumours (66%) of a median size of 24 mm. Local recurrence was 45% at 5 years, lower in multibipolar versus monopolar RFA (22% vs. 55%, p = .007). In treatment-naive patients (n = 45), median overall and recurrence-free survivals were 26 and 11 months, respectively. Tumour size (p = .01) and Child-Pugh B (p = .001) were associated with death. The rate of distant recurrence was 59% at 5 years significantly lower for single tumours of less than 2 (p = .002) or 3 cm (p = .02). In cirrhotic patients naïve of previous treatment (n = 40), overall survival was shorter than in HCC (26 vs 68 months, p < .0001), with more local recurrences (p < .0001). Among distant recurrences, 50% were extrahepatic metastases compared to 12% in HCC (p < .001). CONCLUSION: Multibipolar RFA provides better results in terms of tumour recurrence than monopolar RFA and could be used to treat small iCCA (<3 cm). Adjuvant chemotherapy should be discussed due to the frequent extra-hepatic metastasis at recurrence.

The impact of post-hepatectomy liver failure on long-term survival after liver resection for perihilar cholangiocarcinoma.

BACKGROUND: Although post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain. METHODS: Retrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria. RESULTS: A total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival. CONCLUSION: To achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

Laparoscopic liver resection as a treatment option for intrahepatic cholangiocarcinoma.

Laparoscopic liver resection (LLR) remains controversial in the treatment of intrahepatic cholangiocarcinoma (ICC). The aim of the present study is to investigate the outcomes of LLR for ICC compared to open liver resection (OLR). We retrospectively reviewed patients who underwent surgery for ICC between January 2013 and February 2020. OLR and LLR were compared after propensity score matching (PSM). Overall survival (OS) and recurrence-free survival (RFS) were compared between the matched groups. During the study period, 219 patients met the inclusion criteria (OLR = 170 patients, 77.6%; LLR = 49 patients, 22.4%). Two groups of 43 patients each were analyzed after PSM. The 5-year RFS and OS were 44.6% and 47.9% in the OLR group and 50.9% and 39.8% in the LLR group, respectively. Hospital stay and intensive care unit care were significantly shorter and lower in the LLR group than in the OLR group, respectively. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the OLR group and the LLR group. Multiple tumors and lymph node metastases were predisposing factors for tumor recurrence and death in multivariate analysis. The present study suggests that LLR should be considered in selective ICC because of short hospitalization and similar oncologic outcome and overall survival.