Curative Resection For Intrahepatic Cholangiocarcinoma Research Articles

Survival and progression-free survival in patients undergoing curative resection for intrahepatic cholangiocarcinoma.

562 Background: Intrahepatic cholangiocarcinoma (iCCA) is a relatively rare but increasingly prevalent form of primary liver cancer. Surgical resection with negative margins is the mainstay of the treatment for patients with resectable-iCCA. However, given the rarity of iCCA and its low resectability rate, well-defined prognostic markers and outcomes for patients undergoing curative hepatectomy are lacking. We aimed to analyze the characteristics and outcomes of patients undergoing liver resection for iCCA. Methods: All consecutive patients with confirmed iCCA who underwent hepatectomy between 7/2006-3/2023 at our institution were included. Patients who received neoadjuvant therapy were excluded. Demographic, clinical, radiological, histopathological, recurrence, and survival data were collected. Overall survival was calculated from the date of liver resection to the date of death or last clinical encounter. Continuous variables are reported as median and interquartile range (IQR) 1 and IQR3, and categorical variables as counts and percentages. Results: A total of 83 patients (43 male, 40 female) were included in the final analysis. The median age at resection was 67 years (58.0-74.0). Histologically proven liver disease was present in 30.12% and liver cirrhosis was present in 9.63% of patients. Among all patients, hypertension was present in 61.44%, diabetes mellitus in 25.30%, inflammatory bowel disease in 7.22%. The median tumor size was 4.4 cm (3.0-6.2). Tumor histologic grade was 55.42% moderately differentiated tumor, 37.3% poorly differentiated tumor, and 7.22% well differentiated tumor. Of all patients, 37.66% had lymph node invasion, 35.61% had perineural invasion, and 30.76% had vascular invasion on liver histology. Positive surgical margins were present in 20.73% of patients. The duration from liver resection to the last follow-up or death was 1.6 years (0.80-3.20). The 1-, 3-, and 5-year recurrence-free survival rates were 72.78, 34.95, and 15.88% respectively. The 1-, 3-, and 5-year overall survival rates were 90.9%, 65.9, 44.2%, respectively. Advanced iCCA stage at diagnosis ( p<0.001), presence of lymph node metastasis ( p=0.03), vascular invasion ( p=0.02), and age<50 ( p=0.01) were associated with significantly worse overall survival. There was no statistically significant survival difference between patients with concurrent liver disease and those without (6.88 vs 4.35 years, p=0.46.). Conclusions: Our results demonstrate that iCCA carries a substantial risk of recurrence despite curative resection. The presence of advanced stage at diagnosis, lymph node involvement, vascular invasion, and age<50 were associated with significantly worse overall survival. Liver disease had no significant effect on the survival outcomes. Predictive markers of recurrence and survival in patients vary in the literature and remain to be validated.

A surgical strategy for intrahepatic cholangiocarcinoma — the hilar first concept

PurposeThe present study assesses long-term overall survival (OS) and disease-free survival (DFS) after curative resection for intrahepatic cholangiocarcinoma (ICCA) depending on resection margin (RM) status and lymph node (LN) status.MethodsClinical data of all consecutively resected patients with ICCA at a single high-volume center between 2005 and 2018 were collected. Minimum follow-up was 36 months. Perioperative and long-term oncological outcome was assessed.ResultsOne hundred ninety-two cases were included in the analysis. Thirty- and 90-day-mortality was 5.2% (n = 10) and 10.9% (n = 21). OS was 26 months with 1-, 2-, and 5-year-OS rates of 72%, 53%, and 26%. One-, 2-, and 5-year-DFS rates were 54%, 42%, and 35% (N0 vs. N1: 29 vs. 9 months, p = 0.116). R1 was not found to be an independent risk factor for reduced survival in the overall cohort (p = 0.098). When differentiating according to the LN status, clear resection margins were significantly associated with increased DFS for N0 cases (50 months vs. 9 months, p = 0.004). For N1 cases, no significant difference in DFS was calculated for R0 compared to R1 cases (9 months vs. 9 months, p = 0.88). For N0 cases, clear resection margins > 10 mm were associated with prolonged OS (p = 0.048).ConclusionFor N1 cases, there was no significant survival benefit when comparing R0 versus R1, while the complication rate remained high for the extended resection types. In view of merging multimodal treatment, the hilar first concept assesses locoregional LN status for optimal surgical therapy.

Incidence of metachronous peritoneal metastases for intrahepatic cholangiocarcinoma after curative resection: A single center cohort analysis.

e16199 Background: The impact of metachronous peritoneal metastases (m-pm) on survival after curative resection for intrahepatic cholangiocarcinoma (iCCA) is poorly understood, while there is some knowledge to the occurrence of pulmonary and hepatic metastases. Studies are needed to analyze the impact of advanced metastatic disease for m-pm for iCCA after curative resection. Methods: At the Charité - Universitätsmedizin Berlin, a total of 1979 patients with the general diagnosis of cholangiocellular carcinoma were discussed in interdisciplinary tumor conferences from 2010 to 2022. Results: At the Charité - Universitätsmedizin Berlin, a total of 1979 patients with the general diagnosis of cholangiocellular carcinoma were discussed in interdisciplinary tumor conferences from 2010 to 2022. iCCA was present in 269 cases and proven histopathological results were documented at our hospital in 227 patients. Out of these, 209 patients underwent curative resection, while no advanced tumor disease leading to termination of the indicated operation were found. Two patients presented limited synchronous peritoneal metastases (s-pm) intraoperatively. The postoperative histopathological result presented N0-status in 113 patients and N+-status in 96 patients. Metachronous metastases were diagnosed in 17 patients after 103 months on average with a mean overall survival (OS) of 108 months. Regarding postoperative complications >3b Clavien-Dindo after the initial surgery one patient died in the early postoperative follow-up within the first 30 days. Complete radical resection (R0) was achieved in 133 patients, while R1-status was recorded in 28 patients. Furthermore seven m-pm patients additionally presented hepatic metastases, five m-pm patients pulmonary metastases, while one m-pm patient showed simultaneous hepatic and pulmonal metastases and one other m-pm patient developed even hepatic, pulmonal and osseous metastases. Neoadjuvant oncologic therapy was performed in two patients, adjuvant therapy was applied in six patients prior to the diagnosis of m-pm. Again, a total of five patients received palliative therapy after diagnosis of m-pm. Nevertheless, one patient underwent pulmonary metastectomy. Conclusions: The primary aim regarding the two s-pm patients was immediate postoperative surgical outcome without complications (>3a according to Clavien-Dindo) and was feasible, regarding the prognostic impact of s-pm for surgical resectability; curative resection seems to be an option. The primary aim for m-pm was OS, while promising outcomes were shown in this study.

ASO Visual Abstract: Dynamic Prediction of Survival After Curative Resection of Intrahepatic Cholangiocarcinoma: A Landmarking-Based Analysis.

ASO Visual Abstract: Dynamic Prediction of Survival After Curative Resection of Intrahepatic Cholangiocarcinoma: A Landmarking-Based Analysis.

ASO Author Reflections: Dynamic Prediction of Survival After Curative Resection of Intrahepatic Cholangiocarcinoma: A Landmarking-Based Analysis.

ASO Author Reflections: Dynamic Prediction of Survival After Curative Resection of Intrahepatic Cholangiocarcinoma: A Landmarking-Based Analysis.

Factors of Early Recurrence After Resection for Intrahepatic Cholangiocarcinoma.

Two-thirds of patients undergoing liver resection for intrahepatic cholangiocarcinoma experience recurrence after surgery. Our aim was to identify factors associated with early recurrence after resection for intrahepatic cholangiocarcinoma. Patients with intrahepatic cholangiocarcinoma undergoing curative intent resection (complete resection and lymphadenectomy) were included in two centers between 2005 and 2021 and were divided into three groups: early recurrence (< 12months after resection), delayed recurrence (> 12months), and no recurrence. Patients experiencing early (< 90days) postoperative mortality were excluded. Among 120 included patients, 44 (36.7%) experienced early recurrence, 24 (20.0%) experienced delayed recurrence, and 52 (43.3%) did not experience recurrence after a median follow-up of 59months (IQR: 26-113). The median recurrence-free survival was 16months (95% CI: 9.6-22.4). Median overall survival was 55months (95% CI: 45.7-64.3), while it was 25months for patients with early recurrence (p < 0.001). Patients with early recurrence had significantly larger tumors (59.1% of tumors > 70mm in early vs. 58.3% in delayed vs. 26.9% in no recurrence group, p = 0.002), multiple lesions (65.9% vs. 29.2% vs. 11.5%, p < 0.001), and positive lymph nodes (N +) (38.6% vs. 37.5% vs. 11.5%, p = 0.005). In multivariable analysis, presence of multiple lesions (OR: 9.324; 95% CI: 3.051-28.489; p < 0.001) and positive lymph nodes (OR: 3.307. 95% CI: 1.001-11.011. p = 0.05) were associated with early recurrence. Early recurrence after curative resection of intrahepatic cholangiocarcinoma is frequent and is associated with the presence of multiple lesions and positive lymph nodes, raising the question of surgery's futility in this context.

Recurrence after Curative Resection for Intrahepatic Cholangiocarcinoma: How to Predict the Chance of Repeat Hepatectomy?

(1) Background: Tumor recurrence after liver resection (LR) for intrahepatic cholangiocarcinoma (ICC) is common. Repeat liver resection (RLR) for recurrent ICC results in good survival outcomes in selected patients. The aim of this study was to investigate factors affecting the chance of resectability of recurrent ICC. (2) Methods: LR for ICC performed between January 2001 and December 2020 were retrospectively reviewed. Patients who had undergone first LR were considered for the study. Data on recurrences were analyzed. A logistic regression model was used for multivariable analysis of factors related to RLR rate. (3) Results: In total, 140 patients underwent LR for ICC. Major/extended hepatectomies were required in 105 (75%) cases. The 90-day mortality was 5.7%, Clavien–Dindo grade 3, 4 complications were 9.3%, N+ disease was observed in 32.5%, and the median OS was 38.3 months. Recurrence occurred in 91 patients (65%). The site of relapse was the liver in 53 patients (58.2%). RLR was performed in 21 (39.6%) patients. Factors that negatively affected RLR were time to recurrence ≤12 months (OR 7.4, 95% CI 1.68–33.16, p = 0.008) and major hepatectomy (OR 16.7, 95% CI 3.8–73.78, p < 0.001) at first treatment. Survival after recurrence was better in patients who underwent RLR as compared with not resected patients (31 vs. 13.2 months, p = 0.02). (4) Conclusions: Patients with ICC treated at first resection with major hepatectomy and those who recurred in ≤12 months had significantly lower probability to receive a second resection for recurrence.

Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

BackgroundPlasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear.MethodsTo evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors.ResultsResults showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs.ConclusionsPeritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

Redefining Conditional Overall and Disease-Free Survival After Curative Resection for Intrahepatic Cholangiocarcinoma: a Multi-institutional, International Study of 1221 patients

ObjectivesTo assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC). MethodsCS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at “x” years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at “x” years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for “x” years postoperatively. ResultsAmong 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence. ConclusionCS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence.

Failure patterns after curative resection for intrahepatic cholangiocarcinoma: possible implications for postoperative radiotherapy

BackgroundTo explore the patterns of failures and areas at highest risk of recurrence for postoperative intrahepatic cholangiocarcinoma (IHCC), with the aim to guide IHCC adjuvant radiotherapy.MethodsPatients with IHCC who had undergone radical surgery at our institution from July 2010 to August 2017 were retrospectively analyzed. The survival and prognostic factors were analyzed by univariate and multivariate analysis. All sites of recurrence were found out and classified as the surgical margin, regional lymph nodes, liver remnant and distant metastasis. According to the recurring area at highest risk, the target volume of adjuvant radiotherapy was proposed.ResultsThe median follow-up time was 23.5 months (2–85 months). The median recurrence free survival (RFS) and overall survival (OS) were 12.1 months and 24.8 months, respectively. Seventy-three (73/127, 57.5%) IHCC patients developed tumor recurrence. Initial recurrences occurred in the potential postoperative radiotherapy (PORT) volume, remnant liver and distant sits were 46 (46/73, 63.0%), 36 (36/73, 49.3%) and 22 (22/73, 30.1%) cases, respectively. Of the 46 patients whose initial recurrence inside the potential PORT volume, 29 (29/73, 39.7%) developed recurrence only inside the potential PORT volume, including 13 tumor bed recurrences, 7 lymph node metastases, and 9 with both tumor bed recurrences and lymph node metastases. The most common lymph node metastases sites were nodes around the abdominal aorta, followed by lymph nodes along the celiac artery, the common hepatic artery, and in the hepatoduodenal ligament.ConclusionsHigh proportion of the recurrences occurred only inside the potential PORT volume, implying adjuvant radiotherapy might improve the local-regional control. Surgical margins and lymph node stations No.16a2, 9, 8, 12, 13, and 14 are suggested to be included in the radiation volume.

Risk Factors and Outcomes of Early Relapse After Curative Resection of Intrahepatic Cholangiocarcinoma.

Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382–2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061–2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095–2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120–2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367–2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331–2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409–2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.

Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma.

Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation. Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.

Recurrence after curative resection for intrahepatic cholangiocarcinoma: how to predict the chance of repeat hepatectomy?

Recurrence after curative resection for intrahepatic cholangiocarcinoma: how to predict the chance of repeat hepatectomy?

Prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative resection: A retrospective cohort study

BackgroundThe aim of this study is to determine the outcomes and prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative hepatectomy. MethodsClinical, histopathological, and treatment data of 53 patients with recurrent cholangiocarcinoma after curative resection from 2005 to 2015 at our institutes were investigated and analyzed by univariate and multivariate analyses (E-788). ResultsRecurrent cholangiocarcinoma occurred in 53 of 97 patients who underwent curative resection for intrahepatic cholangiocarcinoma. The median overall survival after recurrence was 13.6 months (range, 1–55 months). Multivariate analysis revealed that recurrent treatment without surgery (p = 0.0007), gross appearance except for mass-forming type (p = 0.0183) and bile duct invasion at the initial surgery (p = 0.0093) were significant poor prognostic factors in recurrent cholangiocarcinoma. Median survival of patients after surgical treatment for recurrent cholangiocarcinoma was 36.7 months versus 13.1 months in patients who did not undergo surgery (p = 0.029). ConclusionsSurgical treatment, gross appearance in mass-forming type and the absence of bile duct invasion were independent favorable factors for survival among patients with recurrent cholangiocarcinoma. We recommend surgical treatment for localized recurrence, even if it occurs early after the initial hepatectomy.

Major postoperative complications compromise oncological outcomes of patients with intrahepatic cholangiocarcinoma after curative resection – A 13-year cohort in a tertiary center

Hepatectomy is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative complication and oncological outcome has not been defined. We aimed to elucidate the effect of postoperative complication on long-term survival of ICC patients after curative resection. Data of consecutive patients who had curative resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor were excluded. Clinicopathological data and postoperative events were extracted from database for survival analysis. There were 107 patients in our series. Their median age was 61 years. The median follow-up time was 24 months. The median tumor size was 6cm. Major hepatectomy was required in 52.3% of them. The median operation time and blood loss was 439 minutes and 0.9L respectively. R0 resection was achieved in 88.8% of them. The median length of stay was 11 days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major complications were found in 20.6% of them. Patients with postoperative complications had significantly inferior survival than patients without (3-yr DFS 38% vs. 27%, P=0.001; 3-yr overall: 51% vs. 27%, P<0.001). Multivariable analysis showed that postoperative complication was an independent factor associated with disease-free survival (OR 1.9 95% C.I. 1.10-3.24, P=0.021) and overall survival (OR 2.1, 95% C.I. 1.13-3.93, P=0.018). Postoperative complication has a significant impact on ICC patients' long-term survival. Extra measures such as adjuvant chemotherapy should be considered for patients who develop major complications after surgery.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.

The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

Perioperative blood transfusion does not affect recurrence-free and overall survivals after curative resection for intrahepatic cholangiocarcinoma: a propensity score matching analysis

BackgroundWhether perioperative blood transfusions (PBTs) adversely influence oncological outcomes for intrahepatic cholangiocarcinoma (ICC) patients after curative resection remains undetermined.MethodsOf the 605 patients who underwent curative liver resection for ICC between 2000 and 2012, 93 received PBT. We conducted Cox regression and variable selection logistic regression analyses to identify confounding factors of PBT. Propensity score matching (PSM) and Cox regression analyses were used to compare the overall survival (OS) and disease-free survival (DFS) between the patients with or without PBT.ResultsAfter exclusion, 93 eligible patients (15.4%) received PBT, compared with 512 (84.6%) who did not receive PBT; the groups were highly biased in terms of the propensity score (PS) analysis (0.096 ± 0.104 vs. 0.479 ± 0.372, p < 0.001). PBT was associated with an increased risk of OS (HR: 1.889, 95% CI: 1.446–2.468, p < 0.001) and DFS (HR: 1.589, 95% CI: 1.221–2.067, p < 0.001) in the entire cohort. After propensity score matching (PSM), no bias was observed between the groups (PS,0.136 ± 0.117 VS. 0.193 ± 0.167, p = 0.785). In the multivariate Cox analysis, PBT was not associated with increased risks of OS (HR: 1.172, 95% CI: 0.756–1.816, p = 0.479) and DFS (HR: 0.944, 95% CI: 0.608–1.466, p = 0.799). After propensity score adjustment, PBT was still not associated with OS or DFS after ICC curative resection.ConclusionsThe present study found that PBT did not affect DFS and OS after curative resection of ICC.

Proton beam therapy as a rising option in treating intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) comprises about 10–15% of primary liver cancers, and the incidence is increasing (1,2). The only curative option is surgical resection, and the resectability rate at the time of diagnosis varies from 19% to 74% (3-6). Recent study showed the recurrence rate of 71% after curative resection of ICC, and 59.8% of them had local recurrence only (7). Unresectable ICC has a poor survival which the median overall survival (OS) is around 3 months when untreated (8) and palliative chemotherapy has shown survival benefit. ABC-02 trial showed biliary tract cancer treated with gemcitabine plus cisplatin had better survival than those treated with gemcitabine only (9), and now considered as the first choice chemotherapy in the treatment of unresectable or recurred ICC.

Pathological Confirmation of Para‐Aortic Lymph Node Status as a Potential Criterion for the Selection of Intrahepatic Cholangiocarcinoma Patients for Radical Resection with Regional Lymph Node Dissection

Para-aortic lymph node (PAN) metastasis traditionally has been defined as distant metastasis. Many studies suggest that lymph node metastasis in intrahepatic cholangiocarcinoma (ICC) is one of the strongest prognostic factors for patient survival; however, the status of the PAN was not examined separately from regional lymph node metastasis in these reports. Here, we investigated whether regional lymph node metastasis without PAN metastasis in ICC can be classified as resectable disease and whether curative resection can have a prognostic impact. Between 1998 and 2010, a total of 47 ICC patients underwent hepatic resection and systematic lymphadenectomy with curative intent. We routinely dissected the PANs and had frozen-section pathological examinations performed intraoperatively. If PAN metastases were identified, curative resection was abandoned. We retrospectively investigated the prognostic factors for patient survival after curative resection for ICC without PAN metastases, with particular attention paid to the prognostic impact of lymphadenectomy. Univariate analysis identified concomitant portal vein resection, concomitant hepatic artery resection, intraoperative blood loss, intraoperative transfusion, and residual tumor as significant negative prognostic factors. However, lymph node status was not identified as a significant prognostic factor. The 14 patients with node-positive cancer had a survival rate of 20 % at 5 years. Based on multivariate analysis, intraoperative transfusion was an independent prognostic factor associated with a poor prognosis (risk ratio = 4.161; P = 0.0056). Regional lymph node metastasis in ICC should be classified as resectable disease, because the survival rate after surgical intervention was acceptable when PAN metastasis was pathologically negative.

Intrahepatic Cholangiocarcinoma: Prognostic Factors After Surgical Resection

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor. The resectability rate is low because at the time of diagnosis this disease is frequently beyond the limits of surgical therapy. Curative resection (R0) is the most effective treatment and the only therapy associated with prolonged disease-free survival. Based on the gross appearance of the tumor the Liver Cancer Study Group of Japan (LCSGJ) defined three types: mass-forming type (MF), periductal infiltrating type (PI), intraductal growth (IG) type. The prognostic significance of gross type has been demonstrated in Eastern countries, but this issue has not been clarified in Western countries. The aim of this study was to identify the prognostic factors for survival in a group of patients submitted to surgical resection for ICC. Between 1990 and 2007 a total of 81 consecutive patients with ICC were submitted to surgery. Patients with peritoneal carcinomatosis, extensive vascular involvement, or multiple intrahepatic metastases were excluded from surgical resection. Tumors were classified according to TMN stage (6th edition, 2002) and LCSGJ gross type classification. Tumor gross appearance on the cut surface was categorized into the following types according to the classification proposed by the Liver Cancer Study Group of Japan: MF, PI, or IG type. During the study period 52 patients were submitted to surgical resection with curative intent, whereas in 29 patients surgery was limited to explorative laparotomy. Curative resection (R0) was achieved in 43 patients (83%); and a major hepatic resection was performed in 63% (33/52) of the patients. Extrahepatic bile duct resection was carried out in 36% (19/52) of cases. According to the LCSGJ classification, the MF type was present in 34 patients (65%), the MF + PI type in 13 (25%), the PI type in 3 (6%), and the IG type in 2 (4%). Overall median survival time was 40 months, with a 1-, 3-, and 5-year actuarial survival rates of 83%, 50%, 20%, respectively. Survival was significantly related to the macroscopic gross type, with a median survival of 50 months for patients with the MF type, 19 months for the MF + PI type, 15 months for the PI type, and 17 months for the IG type. At univariate analysis, the macroscopic gross appearance of the tumor, the presence of lymph node metastasis, involvement of extrahepatic bile ducts, the presence of macroscopic vascular invasion, and positive resection margins were significant related to survival. At multivariate analysis, macroscopic vascular invasion and lymph nodes metastases were significant related to survival with hazard ratios of 4.11 and 2.79, respectively. Further statistical analyses were carried out to identify the relation between macroscopic gross type and prognosis. We identified that the MF + PI type tumors were significantly associated with negative prognostic factors, such as the involvement of extrahepatic bile ducts, the presence of lymph nodes metastases, the presence of macroscopic vascular invasion, the presence of perineural invasion, and higher T stage. Curative resection of ICC is the only therapy that can achieve long-term survival. The best results were observed in patients who underwent R0 resection for MF tumors without lymph node metastases or vascular invasion. Important predictive factors related to poor survival are MF + PI macroscopic tumor type, lymph node metastases, and vascular invasion. In these patients, other therapeutic approaches (i.e., adjuvant or neoadjuvant therapy) should be evaluated to improve results.