Treatment of Intrahepatic Cholangiocarcinoma—A Multidisciplinary Approach

Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use.

The Diagnostic Value of the CA19-9 and Bilirubin Ratio in Patients with Pancreatic Cancer, Distal Bile Duct Cancer and Benign Periampullary Diseases, a Novel Approach

Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent evidence has shown that the ratio between CA19-9 and bilirubin levels supports diagnostic distinction of benign or malignant hepatopancreaticobiliary diseases. Here, we investigate the diagnostic value of this ratio in PDAC, dCCA and benign diseases of the periampullary region in a novel fashion. To address this aim, we enrolled 265 patients with hepatopancreaticobiliary diseases and constructed four logistic regression models on a subset of patients (n = 232) based on CA19-9, bilirubin and the ratio of both values: CA19-9/(bilirubin−1). Non-linearity was investigated using restricted cubic splines and a final model, the ‘Model Ratio’, based on these three variables was fitted using multivariable fractional polynomials. The performance of this model was consistently superior in terms of discrimination and calibration compared to models based on CA19-9 combined with bilirubin and CA19-9 or bilirubin alone. The ‘Model Ratio’ accurately distinguished between malignant and benign disease (AUC [95% CI], 0.91 [0.86–0.95]), PDAC and benign disease (AUC 0.91 [0.87–0.96]) and PDAC and dCCA (AUC 0.83 [0.74–0.92]) which was confirmed by internal validation using 1000 bootstrap replicates. These findings provide a foundation to improve minimally-invasive diagnostic procedures, ultimately ameliorating effective therapy for PDAC and dCCA.

Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery

BackgroundThe metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems.MethodsA total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach.ResultAge at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: −0.079 to 0.147), 0.042 (95% CI: −0.062 to 0.139), and 0.040 (95% CI: −0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: −0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003–0.037), and AJCC 7th N system (0.019; 95% CI: 0.002–0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent.ConclusionsThe LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.

Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression

Aldehyde dehydrogenases (ALDHs) play an essential role in regulating malignant tumor progression; however, their role in cholangiocarcinoma (CCA) has not been elucidated. We analyzed the expression of ALDHs in 8 paired tumor and peritumor perihilar cholangiocarcinoma (pCCA) tissues and found that ALDH3B1 and ALDH3B2 were upregulated in tumor tissues. Further survival analysis in intrahepatic cholangiocarcinoma (iCCA, n = 27), pCCA (n = 87) and distal cholangiocarcinoma (dCCA, n = 80) cohorts have revealed that ALDH3B2 was a prognostic factor of CCA and was an independent prognostic factor of iCCA and pCCA. ALDH3B2 expression was associated with serum CEA in iCCA and dCCA, associated with tumor T stage, M stage, neural invasion and serum CA19-9 in pCCA. In two cholangiocarcinoma cell lines, overexpression of ALDH3B2 promoted cell proliferation and clone formation by promoting the G1/S phase transition. Knockdown of ALDH3B2 inhibited cell migration, invasion, and EMT in vitro, and restrained tumor metastasis in vivo. Patients with high expression of ALDH3B2 also have high expression of ITGB1 in iCCA, pCCA, and dCCA at both mRNA and protein levels. Knockdown of ALDH3B2 downregulated the expression of ITGB1 and inhibited the phosphorylation level of c-Jun, p38, and ERK. Meanwhile, knockdown of ITGB1 inhibited the promoting effect of ALDH3B2 overexpression on cell proliferation, migration, and invasion. ITGB1 is also a prognostic factor of iCCA, pCCA, and dCCA and double-positive expression of ITGB1 and ALDH3B2 exhibits better performance in predicting patient prognosis. In conclusion, ALDH3B2 promotes tumor proliferation and metastasis in CCA by regulating the expression of ITGB1 and upregulating its downstream signaling pathway. The double-positive expression of ITGB1 and ALDH3B2 serves as a better prognostic biomarker of CCA.

‘It’s always in the back of my mind’: understanding the psychological impact of recovery following pancreaticoduodenectomy for cancer: a qualitative study

ObjectivesTen per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. There is limited previous research focusing on psychological well-being; unmet support needs impact negatively on quality of life. This paper reports the psychological impact of a pancreatic cancer diagnosis and subsequent pancreaticoduodenectomy, exploring how patients’ lives alter following surgery and how they seek support.DesignInductive qualitative study involving in-depth semistructured interviews with 20 participants who had undergone pancreaticoduodenectomy for pancreatic or distal biliary duct cancer. Interviews were audiorecorded, transcribed and anonymised, and thematic analysis used principles of constant comparison.SettingSingle National Health Service Trust in Northwest England.ParticipantsPatients were eligible for inclusion if they had had pancreaticoduodenectomy for head of pancreas cancer, periampullary cancer or distal cholangiocarcinoma between 6 months and 6 years previously, and had completed adjuvant chemotherapy.ResultsAnalysis identified the following main themes: diagnosis and decision making around surgery; recovery from surgery and chemotherapy; burden of monitoring and ongoing symptoms; adjusting to ‘a new normal’; understanding around prognosis; support-seeking. Participants seized the chance to have surgery, often without seeming to absorb the risks or their prognosis. They perceived that they were unable to control their life trajectory and, although they valued close monitoring, experienced anxiety around their appointments. Participants expressed uncertainty about whether they would be able to return to their former activities. There were tensions in their comments about support-seeking, but most felt that emotional support should be offered proactively.ConclusionsPatients should be made aware of potential psychological sequelae, and that treatment completion may trigger the need for more support. Clinical nurse specialists (CNSs) were identified as key members of the team in proactively offering support; further training for CNSs should be encouraged. Understanding patients’ experience of living with cancer and the impact of treatment is crucial in enabling the development of improved support interventions.

Outcome of Obstructive Jaundice Patients after Endoscopic Retrograde Cholangiopancreatography

Introduction: Obstructive jaundice is frequently encountered worldwide including Bangladesh. Therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP) is one of the procedures to manage obstructive jaundice. Objectives: To ascertain the outcome of obstructive jaundice patients who underwent ERCP. Materials and Methods: It was a hospital based cross sectional observational study, carried out in Gastroenterology Department of Combined Military Hospital (CMH) Dhaka from May 2017 to May 2019. Total 200 patients were included in the study. Verbal consents were taken from patients. Data were collected with a checklist and analyzed by using SPSS 20. Results: Total 200 patients’ mean age±SD was 56.5±14.5 years with range 21 to 92 years and majority were 41 to 60 years 80(40%) followed by 61 to 80 years 78(39%). Etiology of obstructive jaundice were, benign 137(68.5%) and malignant 63(31.5%). Among the benign: 69(34.5%) were choledocholithiasis, 45(22.5%) biliary stricture, 20(10.0%) papillary stenosis and 3(1.5%) biliary warms. Among the malignant: 24(12.0%) were distal cholangiocarcinoma, 21(10.5%) periampullary tumors, 10(5.0%) Klatskin tumor, 4(2.0%) carcinoma head of pancreas, and 4(2.0%) other malignancy. Mean serum bilirubin level 17.6 mg/dl with minimum 0.6mg/dl, maximum 41.3mg/dl; mean alkaline phosphatase (ALP) level 351.4U/L with minimum 111U/L and maximum 1262U/L; mean alanine aminotransferase (ALT) level 118.8 U/L with minimum 28 U/L, maximum 521 U/L; ERCP were successfully done in 188(94.0%) patients with single attempt 171 (85.5%), repeated sessions 17(8.5%) and 12(6.0%) patients unsuccessful ERCP; complications occurred in 17(8.5%)patients, of whom post-ERCP pancreatitis 9(4.5%) and post procedure cholangitis 4(2.0%)patients. Conclusion: Benign etiologies of obstructive jaundice were more common than malignant one. Both benign and malignant etiology of obstructive jaundice can be successfully managed with ERCP with few complications. JAFMC Bangladesh. Vol 16, No 2 (December) 2020: 27-30

A Safe Start Laparoscopic-assisted Pancreaticoduodenectomy in Songklanagarind Hospital, Thailand: Case Report

Total laparoscopic pancreaticoduodenectomy (PD) is a highly complex procedure. Evidence suggests laparoscopic-assisted PD (LAPD) might be an important link in the process of transition from open PD to total laparoscopic PD. We present the first successful LAPD in a female patient with distal cholangiocarcinoma at Songklanagarind Hospital, Thailand in July 2018. The postoperative course was satisfactory without the clinical relevance of complications. No evidence of recurrence was found after 35 months of follow-up. The results ensured the feasibility and safety of LAPD in the initial phase; regarding both complications and oncological outcomes in a high-volume center for open PD.

A Nomogram Based on the Log Odds of Positive Lymph Nodes Predicts the Prognosis of Patients With Distal Cholangiocarcinoma After Surgery

Background: Lymph node (LN) metastasis is considered one of the most important risk factors affecting the prognosis of distal cholangiocarcinoma (DCC). This study aimed to demonstrate the superiority of log odds of positive lymph nodes (LODDS) compared with other LN stages, and to establish a novel prognostic nomogram to predict the cancer-specific survival (CSS) of DCC.Methods: From the Surveillance, Epidemiology and End Results (SEER) database, the data of 676 patients after DCC radical operation were screened, and patients were randomly divided into training (n = 474) and validation sets (n = 474). The prognostic evaluation performance of the LODDS and American Joint Commission on Cancer (AJCC) N stage and lymph node ratio (LNR) were compared using the Akaike information criteria, receiver operating characteristic area under the curve (AUC), and C-index. Multivariate Cox analysis was used to screen independent risk factors, and a LODDS-based nomogram prognostic staging model was established. The nomogram's precision was verified by C-index, calibration curves, and AUC, and the results were compared with those of the AJCC TNM staging system.Results:Compared with the other two stages of LN metastasis, LODDS was most effective in predicting CSS in patients with DCC. Multivariate analysis proved that LODDS, histologic grade, SEER historic stage, and tumor size were independent risk factors for DCC. The C-index of the nomogram, based on the above factors, in the validation set was 0.663. The 1-, 3-, and 5-y AUCs were 0.735, 0.679, and 0.745, respectively. Its good performance was also verified by calibration curves. In addition, the C-index and Kaplan-Meier analysis showed that the nomogram performed better than the AJCC TNM staging system.Conclusion:For postoperative patients with DCC, the LODDS stage yielded better prognostic efficiency than the AJCC N and LNR stages. Compared with the AJCC TNM staging system, the nomogram, based on the LODDS, demonstrated superior performance.