Perihilar cholangiocarcinoma presents unique challenges in perioperative management, requiring a comprehensive approach to optimize patient outcomes.
This case study focuses on the multidisciplinary management and innovative interventions performed in the perioperative care of a patient with hilar cholangiocarcinoma.
A comprehensive assessment and treatment strategy involving neoadjuvant therapy and interventional radiology techniques were implemented. Neoadjuvant chemotherapy was administered to reduce tumor size and improve resectability. The crucial role of interventional radiology in managing postoperative complications is highlighted, particularly in the case of massive pulmonary embolism.
The neoadjuvant therapy successfully reduced tumor size, enabling an R0 surgical resection. Additionally, interventional radiology interventions, such as percutaneous pharmaco-mechanical thrombectomy, effectively addressed the life-threatening complication of massive pulmonary embolism.
This article highlights the importance of a collaborative, multidisciplinary approach in managing complex oncological surgeries, especially regarding the hospital’s rescue capacity for severe postoperative complications. Emergent management with interventional radiology had a central role in resolving life-threatening complications.
Cholangiocarcinoma (CCA) is a rare neoplasm, with high mortality, originating in the bile ducts. Its incidence is higher in Eastern countries due to the endemic prevalence of liver parasites. Factors such as metabolic syndrome, smoking, and pro-inflammatory conditions are also linked to the disease. Clinical features include asthenia, abdominal pain, cholestasis, and increased serum levels of CEA and CA19-9.
The aim of this study was to evaluate CCA prevalence, survival, and potential prognostic and therapeutic implications in a patient cohort and assess correlations with clinical laboratory data and possible associated risk factors.
This is a retrospective study of the clinical and histological data of patients diagnosed with CCA at Santa Casa de Misericórdia in Porto Alegre, Brazil, between 2016 and 2021.
There was a 56% prevalence of CCA in women, with intrahepatic localization in 55.4% of cases and unifocality in 85.6% of patients. The mean age of the patients was 63 years (26–89 years), with a mean tumor size of 5.5 cm. The median survival time was 7 months (0 to >50). CA19-9 was altered in 81% of patients, whereas GOT/GPT was altered in 62.5% and gamma-glutamyl transferase/alkaline phosphatase/bilirubin in 69.1% of patients. Mortality was higher among patients with extrahepatic CCA.
Risk factors such as smoking, cholecystectomy, cirrhosis, intrahepatic lithiasis, and transplantation should be considered individually by the attending physician for radiological monitoring and incidental discovery of the neoplasm. Lack of timely identification by the attending physician can delay diagnosis, increasing mortality.
Intrahepatic cholangiocarcinoma (iCCA) was considered a contraindication for liver transplantation. However, recent studies have shown that highly selected cases of patients with a good response to neoadjuvant therapy may achieve acceptable survival rates when following liver transplantation.
To present two cases of patients with iCCA, without extrahepatic disease, who underwent living donor liver transplantation after receiving neoadjuvant chemotherapy.
Two cases of patients with histopathological diagnosis of locally advanced iCCA, ineligible for resection and without evidence of extrahepatic disease, are presented.
These patients underwent at least nine sessions of neoadjuvant chemotherapy, including Gemcitabine and Cisplatin, with or without the addition of immunobiological agents, resulting in a radiological tumor response. They subsequently underwent living donor liver transplantation. The average follow-up time was 15 months, with no clinical or radiological signs of disease.
In well-selected patients without extrahepatic disease, living donor liver transplantation represents a potential therapeutic option for iCCA.
Liver transplantation represents the best therapeutic modality in end-stage chronic liver disease, severe acute hepatitis, and selected cases of liver tumors.
To describe a double retransplant in a male patient diagnosed with Crohn's disease and complicated with primary sclerosing cholangitis, severe portal hypertension, and cholangiocarcinoma diagnosed in the transplanted liver.
A 48-year-old male patient diagnosed with Crohn's disease 25 years ago, complicated with primary sclerosing cholangitis and severe portal hypertension. He underwent a liver transplantation in 2018 due to secondary biliary cirrhosis. In 2021, a primary sclerosing cholangitis recurrence was diagnosed and a liver retransplantation was indicated. Recipient's hepatectomy was very difficult by reason of complex portal vein thrombosis requiring extensive thromboendovenectomy. Intraoperative ultrasound with liver doppler evaluation was performed. Two suspicious nodules were incidentally diagnosed in the donor's liver and immediately removed for anatomopathological evaluation.
After pathological confirmation of carcinoma, probable cholangiocarcinoma, at frozen section, the patient was re-listed as national priority and a new liver transplantation was performed within 24 hours. The patient was discharged after 2 weeks.
The screening for neoplasms in donated organs should be part of our strict daily diagnostic arsenal. Moreover, we argue that, for the benefit of an adequate diagnosis and the feasibility of a safer procedure, the adoption of imaging tests routine for the liver donor is essential, allowing a reduction of the costs and some potential risks of liver transplant procedure.
Cholangiocarcinoma is an aggressive neoplasm that usually requires palliative biliary drainage. Photodynamic therapy (PDT) has been described as a successful adjunct treatment to malignant biliary obstruction.
To describe the use of digital cholangioscope to help provide laser light during biliary PDT session using locally developed light source.
Patient receives intravenous photosensitizer 24 h before the procedure. It starts with a regular duodenoscopy. After identification of the major papilla and retrograde cannulation, the digital cholangioscope is introduced into the common bile duct. Then, the cholangioscopic examination helps to identify the neoplastic stricture. Under direct visualization lighting catheter is advanced through the cholangioscope. Repositioning is recommended every centimeter to cover all strictured area. At the end of the procedure, a final cholangioscopy assesses the bile duct for the immediate result and adverse events.
This procedure was applied in one 82-year-old male due to obstructive jaundice in the last two months. EUS and ERCP revealed a severe dilation of the common bile duct associated with choledocholithiasis. Besides, was revealed dilation of hepatic duct up to a well-circumscribed hypoechoic solid mass measuring 1.8x2 cm compressing the common hepatic duct. The mass was deemed unresectable and the patient was referred for palliative treatment with PDT. He remained asymptomatic for three months. He perished due to complications 15 months after the PDT session.
Digital cholangioscopy-guided biliary PDT is feasible and seems safe and effective as an adjunct modality in the palliation of extrahepatic cholangiocarcinoma.
Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy.
To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma.
The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages.
A protocol proposal for this disease is presented, which needs to be validated for clinical use.
The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.
Biliary intraepithelial neoplasia (BilIN) is defined as a precursor lesion of invasive adenocarcinoma and it can develop both in intrahepatic and extrahepatic bile ducts. BilIN grossly presents as flat lesions but is usually macroscopically and radiologically unidentifiable10,21. Interestingly, in the last decades due to the spread of imaging techniques, focal intrahepatic biliary strictures (FIHS) are more commonly incidentally founded in clinical practice. It is currently unknown which is their correct management and in what percentage they can harbor pre-neoplastic alterations (as BilIN) or malignancy20. Due to the concomitant increase in western countries of intrahepatic cholangiocarcinoma, it would be useful to understand the natural history of FIHS, as they can represent a radiological manifestation of underlying pre-malignant disease: in that perspective, the ideal treatment could be an early surgery to prevent cholangiocarcinoma3,18.
Cholangiocarcinoma is the most common biliary tract malignancy, with a well known unfavorable prognosis. Currently, surgery is the only potential curative treatment but, unfortunately, the majority of patients are diagnosed at late stage or are found to be unresectable during explorative laparotomy3. Interestingly, during the last three decades, the incidence of the intrahepatic subtype of cholangiocarcinoma has increased in Western Europe18.
Cholangiocarcinoma of intrahepatic and extrahepatic bile ducts is known to develop through a multistep carcinogenesis sequence, including biliary intraepithelial neoplasia. BilIN is characterized by a flat or micropapillary growth of atypical biliary epithelium. In 2007 Zen et al10. reported the results of the international consensus on its diagnostic criteria and grading.
In the last 20 years, pathologists have identified two main precursors of invasive cholangiocarcinoma, namely BilIN and intraductal papillary neoplasm of bile duct, both currently included in the WHO classification of tumors of digestive system10. As expected, BilIN and intraductal papillary neoplasm have been identified in the bile ducts of patients suffering of primary sclerosing cholangitis, choledochal cyst and hepatolithiasis, all well known risk factors for cholangiocarcinoma. In 2006, Zen et al.22 reported a series of 110 patients with biliary neoplasm associated to hepatolithiasis, differentiating cases of BilIN and intraductal papillary neoplasm by cytokeratin and mucin immunoistochemical staining; in that series, cholangiocarcinomas arising from BilIN developed tubular adenocarcinoma, while those arising from intraductal papillary neoplasm developed either tubular or colloid carcinomas; moreover, those latter seemed to have a better survival16. Regarding the difference in tumorigenic pathways, BilIN lesions seem to have higher expression of the mucin core protein MUC 1, probably favoring a more invasive phenotype with respect to cholangiocarcinomas harboring form IPNB1. Moreover, many studies have supposed BilIN and IPNB to be biliary counterparts of pancreatic intraepithelial neoplasia intraductal papillary neoplasm and intraductal papillary mucinous neoplasm of the pancreas intraductal papillary neoplasm 8,11,13.
Strictly related to the topic of cholangiocarcinoma’s pre-neoplastic lesions, nowadays in clinical practice another issue is emerging, regarding focal undetermined intrahepatic biliary duct strictures.
An appropriate diagnostic evaluation is of paramount importance, because it is currently unknown FIHS’ natural history and if they can harbor malignancy or pre-neoplastic lesions19. Based on the accessibility of the biliary tree and the site of the lesion, biliary strictures can be evaluated by endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. Both techniques allow sampling of the strictures and therapeutic biliary stent placing. However, biliary brushing cytology, as reported by Trikudanathan et al.17 in a recent meta-analysis, has a low sensitivity (not exceeding 43%) in detection of cholangiocarcinoma in primary sclerosing cholangitis patients. The same authors, in another meta-analysis, reported that fluorescence in situ hybridization (FISH) was able to increase the sensitivity up to 68%12.
Another reported technique in the evaluation of indeterminate biliary lesions is the SpyGlass single-operator peroral cholangioscopy4,9. Woo et al.19 reported that overall accuracy of SpyGlass visual assessment and SpyBite biopsy for the diagnosis of malignancy were 96.7% and 73.6%, respectively. Similar results were obtained in a Japanese large prospective multicenter study (95.5% and 70.7%)9. Interestingly, this study reported 10 cases of intrahepatic indeterminate biliary lesions, in which accuracy values decreased (80% and 83.3%). A recent meta-analysis by Sun et al.15, considering the usefulness of this diagnostic tool in determining malignancy in biliary lesions, reported sensitivity and specificity of visual assessment and visual guided biopsy of 90-87% and 69-98%, respectively. Currently, no study has demonstrated the ability of CT scan or MRCP, as well as endoscopic or intraductal ultrasound, to differentiate benign from malignant intrahepatic strictures.
Regarding treatment, due to the undefined possibility of FIHS to harbor malignancy, it has been advocated that stricture should be resected whenever, during the diagnostic work-up, a malignant diagnosis is suspected or of course ascertained. Yeo et al.20, in their review, proposed an interesting algorithm treatment for FIHS: after a two level diagnostic work-up, based on non-invasive and invasive diagnostic tools, in case of supposed benign stricture, cholangioscopy with or without biopsy should be performed. If a benign stricture is confirmed, treatment should be reserved only to symptomatic patients and could be surgical or non-surgical (endoscopic, percutaneous). Regarding the surgical technique, in the last decade, we have assisted to the spreading of laparoscopic liver resection worldwide1 and several cases of laparoscopic liver resection for intrahepatic bile duct dilatation with associated hepatolithiasis, a condition quite similar to FIHS, have been described5,6,15. In our centre, we performed in 2019 two cases of left biliary duct stricture who underwent laparoscopic left hepatectomy with final diagnosis of BilIN10,20. In a retrospective Korean series involving 24 patients who underwent surgical resection for bile duct dilatation without demonstrable mass on pre-operative imaging, Kim et al.7 found in half of patients (n=12) malignancy at the final pathology. From a morphological point of view these patients, compared to those with benign bile duct stricture, showed thickening of bile duct wall ≥5 mm and regional lymph node enlargement on CT scan, abrupt cut-off and bile duct separation on cholangiogram. The prospective series by Seo et al.14 on percutaneous transhepatic cholangioscopy included 17 patients with FIHS without stones: a histopathologic diagnosis was obtained in all patients (9 adenocarcinomas, 1 squamous cell carcinoma, 2 hepatocellular carcinomas, 2 adenomas and 3 benign strictures). Of the nine with bile duct adenocarcinoma, eight underwent surgery and a curative resection was possible in seven patients. Interestingly, five patients had early-stage bile duct cancer in which cancer invasion was limited to the mucosa or fibromuscular layer and there was no evidence of lymph node metastasis.
It is raising the fact that FIHS can harbor pre-neoplastic lesions (BilIN). The diagnostic work-up is often inconclusive in order to rule out malignancy, but in literature cholangioscopy with biopsy is emerging as a promising technique to overcome this issue, even if it is not widespread and available in every center as it deserves a specific training and equipment. Whenever the suspicion of malignancy is moderate to high, we believe that surgery is fully justified, as it can represent a kind of preventive treatment of cholangiocarcinoma. Minimally invasive liver resection in this setting could represent the optimal choice. As high level evidence in this topic is still lacking in literature, we call for national and international registers to address the issue of diagnosis and management of focal intrahepatic undetermined strictures.
Desenvolvido por Surya MKT