Distal Cholangiocarcinoma Research Articles

A Lymph Node Ratio Nomogram Based Prognostic Model for Resected Distal Cholangiocarcinoma

Introduction: Several factors have been described as prognostic factor for resected distal cholangiocarcinoma (dCC), among which lymph node metastasis that can be presented as pN0-N1-N2 and lymph node ratio (LNR). This study aimed to evaluate the prognostic value of LNR on survival and to establish a novel prognostic nomogram to predict the cancer-specific recurrence-free survival (RFS) of dCC. Methods: Between December 2006 and September 2020, patients who underwent pancreaticoduodenectomy (PD) for dCC in 10 centers were identified. Multivariate Cox analysis was used to screen independent risk factors among several prognostic factors. A nomogram prognostic staging model was established, and precision was verified by C-index. Results: A total of 415 cases have been included. Cox regression multivariate analysis indicated the LNR15% (hazard ratio [HR] 2.442, 95% CI 1.348-4.425, p = 0.003), as an independent prognostic factor for recurrence-free survival (RFS) with perineural invasion (HR 3.100, 95% CI 1.183-8.122, p = 0.021) and the radicality of PD (HR 2.276, 95% CI 1.223-4.234, p = 0.009). The C-index of the nomogram, based on the above factors, in the validation set was 0.8. Conclusion: LNR yielded a better prognostic efficiency for RFS than the American Joint Committee on Cancer N stage. The nomogram based on LNR can provide a more accurate prognosis for patients with resected dCC.

S37 The Impact of Early Detection of Malignant Biliary Obstruction by Endoscopic Ultrasound on Clinical Outcomes After Surgical Resection

Introduction: Computerized tomography (CT) scan and endoscopic ultrasound (EUS) are the main diagnostic tools for detecting periampullary cancers. EUS allows the detection of small tumors missed by CT scan in patients presenting with bile duct obstruction. However, the impact of EUS in diagnosing small tumors on clinical outcomes is yet to be explored. This study aimed to compare the tumor recurrence rate and survival benefit of patients following pancreaticoduodenectomy (PD) for periampullary cancers detected by abdominal CT vs. EUS after negative CT. Methods: A retrospective review of the EUS and surgery database from 2009 to 2021. The patients who underwent PD for periampullary cancer were recruited. The patients were divided into CT-guided surgery group (CT group) and EUS-guided surgery group (EUS group). The clinical outcomes between the 2 groups were compared. Results: 429 patients were enrolled. 372 patients were diagnosed by CT scan, and EUS diagnosed 57 patients after CT scans failed to detect the cause of bile duct obstruction. The mean age was 64.7+ 11.9 years. The common presentations included jaundice (79.0 %) and weight loss (66.9%). Pancreatic adenocarcinoma (PDAC) was the most common cancer (43.6%), followed by ampullary cancer (32.4%), distal cholangiocarcinoma (14.2%), and duodenal cancer (9.8%). There were no differences in patient demographics between the two groups regarding age, gender, and underlying diseases. Patients in the CT group had higher serum bilirubin (p=0.025), higher serum alkaline phosphatase (p=0.047), lower serum hematocrit (p=0.043), and larger CBD diameter (p=0.005) compared to the EUS group. The T and M staging were not different between the two groups; however, the percentage of patients with nodal metastasis was higher in the CT group (p=0.014). Multivariate analysis showed a trend towards higher recurrence and 5-year mortality rate in the CT group with odds ratios (OR) of 1.33 (95% CI, 0.82-2.13) and 1.43 (95% CI, 0.84-2.42), respectively. Subgroup analysis of PDAC and cholangiocarcinoma demonstrated a significantly higher mortality rate of patients in the CT group with an OR of 2.82 (95% CI, 1.14-6.99, p=0.026) and a trend toward a higher recurrence rate after surgery with the OR of 1.45 (95% CI, 0.80-2.66) compared to the EUS group. Conclusion: EUS added a diagnostic value in the early detection of periampullary cancers, which may lead to a survival benefit, especially in PDAC and cholangiocarcinoma.

Five-year follow-up after pancreatoduodenectomy performed for malignancy: A single-centre study.

The aim of this study was to describe short- and long-term outcomes of patients who underwent pancreatoduodenectomy (PD) at a typical United Kingdom hepatopancreatobiliary unit. A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (PDAC), ampullary adenocarcinoma (AA), or distal cholangiocarcinoma (CC) from September 1st, 2006 to May 31st, 2015 was carried out. The following information was obtained: demographics, comorbidities, preoperative investigations, neoadjuvant treatment, operative details, postoperative management, complications, adjuvant treatment, five-year recurrence, and five-year survival. Effects of selected preoperative variables on short- and long-term outcomes were investigated. Of 271 included patients, 57.9% had PDAC, 25.8% had AA, and 16.2% had CC. In total, 67.9% experienced morbidity and 17.3% developed a Clavien-Dindo grade ≥ III complication. The 90-day mortality was 3.3%. Clinically-relevant postoperative pancreatic fistula, bile leak, gastrojejunal leak, postpancreatectomy haemorrhage and delayed gastric emptying affected 8.1%, 4.1%, 0.0%, 9.2%, and 19.9% of patients, respectively. American Society of Anesthesiologists grade III-VI correlated with overall morbidity (p = 0.002) and major morbidity (p = 0.009), but not 90-day mortality or five-year survival. The same pattern was observed in patients with a preoperative serum bilirubin > 29 μmol/L and/or a neutrophil/lymphocyte ratio > 3.1. Five-year cancer recurrence and five-year survival were 68.3% and 22.5%, respectively. PDAC patients had higher five-year recurrence but lower five-year survival rates (both p = 0.001). In our series, the majority of patients experienced a complication. However, few patients experienced major morbidity. Surgical risk factors did not affect five-year survival.

FGFR2 Inhibition in Cholangiocarcinoma.

Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10-22%) and the nearly exclusive occurrence of FGFR2 fusions in 10-15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.

Robotic approach mitigates the effect of major complications on survival after pancreaticoduodenectomy for periampullary cancer.

Major complications (MCs) after pancreaticoduodenectomy (PD) are a known independent predictor of worse oncologic outcomes. There are limited data on the effect of major complications on long-term outcomes after robotic PD (RPD). The aim of this study is to compare the effect of MC on overall (OS) and disease-free survival (DFS) after RPD and open PD (OPD). This is a single-center, retrospective review of a prospectively maintained database of all patients undergoing PD for periampullary cancer including ampullary adenocarcinoma, distal cholangiocarcinoma, and duodenal carcinoma. Univariate analysis was performed on all clinical, pathologic, and treatment factors. MCs were defined as Clavien-Dindo ≥ grade 3. Kaplan-Maier survival analysis was performed with log-rank test for group comparison. Multivariable Cox regression analysis was used to identify factors associated with overall survival (OS) in both the OPD and RPD groups. A total of 190 patients with ampullary carcinoma (n = 98), cholangiocarcinoma (n = 55), and duodenal adenocarcinoma (n = 37) were examined over the study period with 61.1% (n = 116) undergoing RPD and 38.9% (n = 74) undergoing OPD. There was no significant difference in patient demographics between the RPD and OPD cohorts. Furthermore, R0 resection rates, tumor size, and lymph node involvement were similar between the RPD and OPD cohorts. OPD had higher rate of MC (40.5% vs 28.3% in RPD, p = 0.011) including clinically relevant pancreatic fistula (25.7% vs 8.6%, p = 0.001) and wound infection (34.5% vs 13.8%, p < 0.001). MCs were associated with a lower OS in the OPD cohort (HR = 2.18, 95%CI 1.0-4.55, p = 0.038). MCs were not associated with OS in the RPD cohort (HR = 1.55, 95%CI 0.87-2.76, p = 0.14). MCs are associated with worse patient outcomes after OPD but not after RPD. Robotic approach mitigates and possibly abrogates the negative effects of MCs on patient outcomes after PD for malignancy and is associated with improved adjuvant chemotherapy completion rates.

Surgical Treatment of Distal Cholangiocarcinoma.

Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract and has a poor prognosis. dCCA is often clinically silent and patients commonly present with locally advanced and/or distant disease. For patients identified with early stage, resectable disease, surgical resection with negative margins remains the only curative treatment strategy available. However, despite appropriate treatment and diligent surveillance, risk of recurrence remains high with nearly 50% of patients experiencing recurrence at 5 years subsequent to surgical resection; therefore, it is prudent to continue to optimize neoadjuvant and adjuvant therapies in order to reduce the risk of recurrence and improve overall survival. In this review, we discuss the clinical presentation, workup and surgical treatment of dCCA.

Middle and distal bile duct carcinoma, retrospective analysis & short-term and long-term outcomes of surgical therapy.

The prognosis of extrahepatic cholangiocarcinoma is dismal and the only way to achieve long-term survival is surgical resection. While pancreatoduodenectomy (PD) is the standard procedure for distal cholangiocarcinoma (distal bile duct cancer; DBDC), bile duct segmental resection (BDR) can be used as an alternative approach for middle bile duct cholangiocarcinoma (middle bile duct cancer; MBDC). The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal bile duct cholangiocarcinoma patients. A retrospective cohort study of consecutive patients treated for MBDC and DBDC with PD or BDR between 1/2009-12/2019. The patients were divided according to the type of surgical resection (PD and BDR group). Demographic, clinicopathological and histopathological data and overall survival (OS) were evaluated in both groups. OS was estimated using the Kaplan-Meier analysis. The study comprised a total of 62 patients - 45 patients (72.6%) in the PD group and 17 (27.4%) in the BDR group. Patients undergoing BDR were significantly older than those receiving PD (p=0.048). Men predominated in the PD group (N=34/45; 75.6%) while more women were included in the BDR group (N=10/17; 58.8%). Median age was higher in the BDR group (p=0.048). Serious morbidity (Clavien-Dindo III-V) (33.3% vs 11.8%), 30-day and 90-day mortality (4.4% vs 0.0% and 8.9% vs 5.9%, respectively) predominated in the PD group although the differences were not statistically significant, as well as a longer hospital stay (16.0 days vs 11.0 days; p=0.002). Pathological assessments revealed comparable numbers of positive lymph nodes in both groups, but a significantly higher number of total resected lymph nodes in the PD group (p.

Surgery of extrahepatic bile duct cancer - current evidence and recommendations.

Extrahepatic cholangiocarcinoma is a rare disease with poor prognosis, requiring comprehensive multidisciplinary management. Only radical resection gives hope for long-term survival. Most patients have either an unresectable disease or their condition does not allow for radical surgery. The method of choice for resectable perihilar cholangiocarcinoma is en-block liver resection including the extrahepatic bile duct, or pancreatoduodenectomy for distal cholangiocarcinoma. Hepatopancreatoduodenectomy can be performed in selected patients if the entire hepato-choledochus is affected. Liver transplantation after neoadjuvant treatment can be also considered in highly selected patients with unresectable perihilar cholangiocarcinoma. These procedures are technically demanding, are associated with high morbidity and relevant mortality, and must be concentrated in tertiary hepatobiliary centers. Preoperative optimization (bile duct drainage, nutrition, portal venous embolization, etc.) plays a crucial role in reducing postoperative morbidity and mortality.

Bcl-xL as prognostic marker and potential therapeutic target in cholangiocarcinoma.

Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-xL , Mcl-1) is particularly important. In this study, we investigated whether antiapoptotic protein patterns are prognostically relevant and potential therapeutic targets in CCA. Bcl-2 proteins were analysed in a pan-cancer cohort from the NCT/DKFZ/DKTK MASTER registry trial (n=1140, CCA n=72) via RNA-sequencing and transcriptome-based protein activity interference revealing high ranks of CCA for Bcl-xL and Mcl-1. Expression of Bcl-xL , Mcl-1, and Bcl-2 was assessed in human CCA tissue and cell lines compared with cholangiocytes by immunohistochemistry, immunoblotting, and quantitative-RT-PCR. Immunohistochemistry confirmed the upregulation of Bcl-xL and Mcl-1 in iCCA tissues. Cell death of CCA cell lines upon treatment with specific small molecule inhibitors of Bcl-xL (Wehi-539), of Mcl-1 (S63845), and Bcl-2 (ABT-199), either alone, in combination with each other or together with chemotherapeutics was assessed by flow cytometry. Targeting Bcl-xL induced cell death and augmented the effect of chemotherapy in CCA cells. Combined inhibition of Bcl-xL and Mcl-1 led to a synergistic increase in cell death in CCA cell lines. Correlation between Bcl-2 protein expression and survival was analysed within three independent patient cohorts from cancer centers in Germany comprising 656 CCA cases indicating a prognostic value of Bcl-xL in CCA depending on the CCA subtype. Collectively, these observations identify Bcl-xL as a key protein in cell death resistance of CCA and may pave the way for clinical application.

Survival and Causes of Death among Patients with Intrahepatic Cholangiocarcinoma in the United States from 2000 to 2018.

Intrahepatic cholangiocarcinoma (iCCA) has shown a substantial increase in mortality globally. On the contrary, perihilar cholangiocarcinoma and distal cholangiocarcinoma have been decreasing. We aim to evaluate the causes of death after iCCA diagnosis. We studied 8,962 patients with iCCA diagnosed between 2000 and 2018 in the United States. The standardized mortality ratio for each cause of death was calculated. We used R software version 3.5 to perform Kaplan-Meier survival tests and covariate-adjusted Cox models. Of the 8,962 patients diagnosed with iCCA, 7,335 (81.8%) died during the follow-up period with a mean age of death of 67.88 years. The highest number of deaths (4,786; 65.2%) occurred within the first year following iCCA diagnosis. 4,832 (66%) were from iCCA, 2,063 (28%) were from other cancers, and 440 (6%) were from non-cancer causes mainly cardiovascular disease. The overall mean survival after 1 year of diagnosis was 40.8% (39.8-41.9); however, the overall mean survival was 9.8% (9-10.5) after 5 years of diagnosis. The multivariable analysis showed that age, sex, stage, and management of iCCA have a statistically significant impact on survival. Following iCCA diagnosis, about 34% died from non-iCCA causes. The most common non-iCCA cancer cause was liver cancer, and cardiovascular disease represents a substantial percentage of non-cancer deaths. Our findings provide insights into how iCCA survivors should be followed up regarding future risks. The management and follow-up should be tailored to the needs of each patient with iCCA.

Treatment and overall survival of four types of non-metastatic periampullary cancer: nationwide population-based cohort study.

Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin. Patients diagnosed with non-metastatic periampullary cancer in 2012-2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan-Meier analysis and multivariable Cox regression analyses, stratified by origin. Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR=0.62; 95% CI 0.55-0.69) and DC (HR=0.69; 95% CI 0.48-0.98), but not AC (HR=0.87; 95% CI 0.62-1.22) and DA (HR=0.85; 95% CI 0.48-1.50). This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA.

Patterns of Post-endoscopic Retrograde Cholangiopancreatography (ERCP) Complications

In the treatment of common bile duct stones and palliative decompression of malignant strictures, endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard. However, there are still concerns about procedure-related complications and patient discomfort. The aim of the study is to evaluate the pattern of post ERCP complications. This prospective observational study was conducted at the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from February to October 2017. A total of one hundred patients who were eligible for ERCP were included in this study but five patients were excluded due to cannulation failure. Clinical examination , biochemical, and radiological investigation were performed before and after ERCP to assess the complication that occurred. The majority of patients in this study were at and below the age of 50 years, with a mean age of 49.74 ± 14.07 years and the age range was between 18 to 80 years. Majority of the subjects were male (54.7%), and male to female ratio was 1.21:1. The highest number of patients were diagnosed as choledocholithiasis (58.9%) followed by proximal cholangiocarcinoma (13.7%), Ca-gallbladder with biliary infiltration (8.4%), Distal cholangiocarcinoma (6.3%), Chronic calcific pancreatitis and Periampullary carcinoma each (3.2%), Suspected SOD &amp; Chronic pancreatitis each (2.1%) and Worm in CBD and benign biliary stricture each (1.1%). In this study, the overall post-ERCP complication was 12.6%, with pancreatitis accounting for 9.4%, bleeding accounting for 2.1%, and cholangitis accounting for 2.1%. From the study, it can be concluded that pancreatitis is the most frequent Post-ERCP complication. Bangladesh Med J. 2021 May; 50(2) : 35-39

Converted-hepatopancreatoduodenectomy for an intraoperative positive ductal margin after pancreatoduodenectomy in distal cholangiocarcinoma.

Pancreatoduodenectomy (PD) is the standard treatment for distal cholangiocarcinoma, and a negative ductal margin (DM0) is indispensable for the long-term survival. When intraoperative frozen sections of ductal margin after PD are positive, converted-hepatopancreatoduodenectomy (C-HPD) is the final option available to gain an additional ductal margin. However, the efficacy of C-HPD remains unclear. Patients who underwent PD or C-HPD for distal cholangiocarcinoma between 2002 and 2019 were analyzed. The type of hepatectomy in C-HPD was restricted to left hepatectomy to prevent posthepatectomy liver failure. Of 203 patients who underwent PD for distal cholangiocarcinoma, 49 patients exhibited intraoperative positive ductal margin (DM1) after PD. Eleven patients underwent C-HPD for intraoperative DM1 after PD, in which intraoperative DM1 with invasive carcinoma (DM1inv) was observed in 3 patients, and intraoperative DM1 with carcinoma in situ (DM1cis) was observed in 8 patients. The median additional ductal margin yielded by C-HPD was 9mm (interquartile range 7-13mm). C-HPD eradicated intraoperative DM1inv in 3 patients, with 2 patients showing DM0 and 1 patient showing DM1cis. Regarding 8 patients who underwent C-HPD for intraoperative DM1cis, 4 patients had DM0, but the others had DM1cis. C-HPD was associated with a high complication rate, but no mortality was observed. The median survival time of patients who underwent C-HPD was 48.8months. C-HPD was able to safely eradicate intraoperative DM1inv after PD. However, the length of the resected bile duct according to C-HPD may not be sufficient to remove intraoperative DM1cis after PD.

Cholangiocarcinoma: a review of the literature and future directions in therapy.

Cholangiocarcinomas (CCA) are a group of rare cancers with an incidence of about 1.26 per 100,000 people. The disease reflects one of three different subtypes: intrahepatic, perihilar or hilar and distal cholangiocarcinoma. The preferred modality of definitive therapy is surgical resection with or without adjuvant therapy, however the majority of patients with this disease do not present at an early stage. Some efforts to improve survival rates have come in the form of offering neoadjuvant therapy prior to surgical resection or liver transplantation. Some new protocols are in the process of development for neoadjuvant therapy. Despite advancements in locally advanced or borderline resectable lesions, most patient present at an advanced stage. The mainstay of treatment for advanced stage disease is chemotherapy regardless of location. The mainstay of treatment in fit patients is the combination of gemcitabine and cisplatin. The addition of nab-paclitaxel to this backbone is currently being evaluated in phase III trial. In addition, the role of targeted therapy is currently being studied extensively through multiple different mutational pathways including isocitrate dehydrogenase-1 (IDH1), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ERBB2 (HER2/neu). CCA remains a significant challenge in medicine, however recent studies have shown that there is significant interest in advancing therapy in the form of neoadjuvant, adjuvant and palliative intent treatment.

Efficacy of Endobiliary Radiofrequency Ablation in Preserving Survival, Performance Status and Chemotherapy Eligibility of Patients with Unresectable Distal Cholangiocarcinoma: A Case-Control Study.

Background: Cholangiocarcinoma is the most common malignancy of the bile ducts causing intrahepatic, hilar, or distal bile duct obstruction. Most jaundiced patients are diagnosed with unresectable tumors in need for palliative bile duct drainage and chemotherapy. Endobiliary radiofrequency ablation (RFA) is an adjuvant technique that may be applied prior to biliary stenting. The aim of our study was to assess the efficacy of endobiliary RFA prior to stent insertion in patients with unresectable distal cholangiocarcinomas. Methods: Twenty-five patients (eight treated with RFA and stenting and 17 treated with stenting alone) were included in a case-controlled study. We prospectively assessed the impact of RFA on the survival rate, the patient performance status, and the preservation of eligibility for chemotherapy based on the patient laboratory profile. Results: Patients treated with RFA prior to stenting proved to have a significantly longer survival interval (19 vs. 16 months, p = 0.04, 95% CI) and significantly better performance status. Moreover, the laboratory profiles of patients treated with RFA has been proven superior in terms of total bilirubin, liver enzymes, and kidney function, thus making patients likely eligible for palliative chemotherapy. Post-ERCP adverse events were scarce in both the study group and the control group. Conclusion: Given the isolated adverse events and the impact on the patient survival, performance, and laboratory profile, RFA can be considered safe and efficient in the management of patients with unresectable distal cholangiocarcinomas.

Patterns of post endoscopic retrograde cholangiopancreatography (ERCP) complications- experience from an university hospital

In the treatment of common bile duct stones and palliative decompression of malignant strictures, endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard. However, there are still concerns about procedure-related complications and patient discom- fort. To evaluate the pattern of the post ERCP complications. This prospective observational study was conducted at the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from February 2017 to October 2017. A total of one hundred patients who were eligible for ERCP were included in this study but five patients were excluded due to cannulation failure. Clinical examination , biochemical, and radiological investigation were performed before and after ERCP to assess the complication that occurred. The majority of patients in this study were under the age of 50, with a mean age of 49.74 }14.07 years between the ages of 18 and 80 years. Males (54.7%) were predominant than female (45.3%) and male to female ratio was 1.21:1. The most common diagnosis was choledocholithiasis (58.9%) followed by proximal cholangiocarcinoma (13.7%), Carcinoma-gallbladder with biliary infiltration (8.4%), Distal cholangiocarcinoma (6.3%), Chronic calcific pancreatitis and Periampullary carcinoma each (3.2%), Suspected SOD &amp; Chronic pancreatitis each (2.1%) and Worm in CBD and benign biliary stricture each (1.1%). In this study, the overall post-ERCP complication rate was 12.6% with pancreatitis accounting for 9.4%, bleeding accounting for 2.1%, and cholangitis accounting for 2.1%. From the study data it can be concluded that pancreatitis is the most frequent Post-ERCP complication. BSMMU J 2022; 15(1): 50-53

SYNCHRONOUS AND METACHRONOUS TUMORS OF THE BILIARY TREE.

Biliary tract cancers arise in the biliary tract epithelium and include intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal extrahepatic cholangiocarcinoma, and gallbladder cancer. These sites are anatomically contiguous and may appear related, but they are heterogeneous with distinct genetic and molecular signatures. Cholangiocarcinoma is the malignant tumor arising from the epithelium of the biliary tract, first histologically described by Durand-Fardel in 1840. Classification as originating from the intra- and extrahepatic biliary epithelium1 is a common way of classifying these tumors as prognosis and behavior are different in both types. Extrahepatic cholangiocarcinomas are further separated like the Bismuth classification; into upper-third or perihilar (including the confluence of the right and left biliary ducts) tumors; middle-third tumors; and distal bile duct tumors. Performance of a marginnegative resection with regional lymphadenectomy remains the cornerstone of successful treatment of cholangipcarcinoma.

The state of therapy modalities in clinic for biliary tract cancer.

Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (iCCA), perihilar and distal cholangiocarcinoma (pCCA and dCCA), and gallbladder carcinoma based on the epithelial site of origin. BTCs are highly aggressive tumors associated with poor prognosis due to widespread metastasis and high recurrence. Surgery is the typical curative-intent treatment, yet the cornerstone of cure depends on the anatomical site of the primary tumor, and only a minority of patients (approximately 30%) has an indication necessitating surgery. Similarly, only a small subset of carefully selected patients with early iCCA who are not candidates for liver resection can opt for liver transplantation. Chemotherapy, target therapy, and immunotherapy are the main treatment options for patients who have advanced stage or unresectable disease. The genetic background of each cholangiocarcinoma subtype has been accurately described based on whole gene exome and transcriptome sequencing. Accordingly, precision medicine in targeted therapies has been identified to be aimed at distinct patient subgroups harboring unique molecular alterations. Immunotherapy such as immune checkpoint inhibitors (ICIs) was identified as antitumor responses in a minority of select patients. Current studies indicate that immunotherapy of adoptive cell therapy represents a promising approach in hematological and solid tumor malignancies, yet clinical trials are needed to validate its effectiveness in BTC. Herein, we review the progress of BTC treatment, stratified patients according to the anatomic subtypes of cholangiocarcinoma and the gene drivers of cholangiocarcinoma progression, and compare the efficacy and safety of chemotherapy, targeted therapy, and immunotherapy, which will be conducive to the design of individualized therapies.

Low preoperative psoas muscle mass index is a risk factor for distal cholangiocarcinoma recurrence after pancreatoduodenectomy: a retrospective analysis

BackgroundThis study aimed to investigate whether preoperative muscle mass is associated with the recurrence of distal cholangiocarcinoma after pancreatoduodenectomy (PD).MethodsWe retrospectively examined 88 patients who had undergone PD for distal cholangiocarcinoma. The preoperative psoas muscle mass index (PMI) was measured using computed tomography as an index of muscle mass. We performed multivariate analysis of factors influencing early recurrence and developed a prognostic survival model using independent risk factors for recurrence.ResultsThe cut-off PMI values for recurrence within 1 year of surgery, determined from the receiver operating characteristic curve, were 5.90 cm2/m2 in males and 3.98 cm2/m2 in females. Multivariate analysis of effects associated with early recurrence within 1 year indicated that low PMI (odds ratio [OR] 9.322; 95% confidence interval [CI] 2.832 − 30.678; p = 0.0002) and lymph node metastasis (OR 5.474; 95% CI 1.620 − 18.497; p = 0.0062) were independent risk factors, and the median recurrence-free survival (RFS) of the low and high PMI groups were 21.6 and 81.0 months, respectively (p = 0.0214). The median RFS for zero, one, and two risk factors of low PMI and lymph node metastasis were as follows: zero variables, median not reached; one variable, 15.3 months; two variables: 6 months.ConclusionsLow preoperative PMI may be a risk factor for distal cholangiocarcinoma recurrence after PD.Trial registrationThe Institutional Review Board of St. Marianna University School of Medicine approved this study prior to commencement of data collection and analysis on October 9, 2020 (IRB no. 5006) and waived the informed consent requirement.

PD-6 DNA methylome as a potential biomarker in biliary brushes and bile fluid samples to differentiate between benign and malignant biliary stenosis

The diagnosis of perihilar and distal cholangiocarcinoma (CCA) remains an important clinical challenge. Current detection methods are mostly based on biliary brushing samples with suboptimal sensitivity and/or specificity, leading to late diagnosis and higher mortality rates.