Major hepatectomy for perihilar cholangiocarcinoma

Background/purpose

Hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as “perihilar cholangiocarcinoma”. The principle of surgical treatment is hemi-hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma.

Methods

Using the Kaplan–Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy.

Results

Right hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1-, 3-, and 5-year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT.

Conclusions

Major hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long-term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins.     

Liver transplantation for unresectable perihilar cholangiocarcinoma

Patients with unresectable, stage I and II perihilar cholangiocarcinoma were treated with neoadjuvant external beam irradiation, brachytherapy, and 5-fluorouracil and/or oral capecitabine prior to liver transplantation. Fifty-six patients underwent treatment between 1993 and 2003. Four patients died and 4 had disease progression prior to completion of neoadjuvant therapy. Forty-eight patients underwent operative staging and 14 had findings precluding transplantation. Twenty-eight patients underwent transplantation and 6 patients are awaiting transplantation. Three patients died from perioperative complications, and 4 developed recurrent disease 22 to 63 months after transplantation. Actuarial patient survival was 54% at 5 years for all 56 patients, 64% for 48 operatively staged patients, and 84% for 34 patients with negative staging operations. Actuarial survival was 88% at 1 year and 82 % 5 years after transplantation. Neoadjuvant chemoradiotherapy with liver transplantation achieves excellent results for patients with localized, regional lymph node negative, hilar cholangiocarcinoma.     

Surgical morbidity in the first year after resection for perihilar cholangiocarcinoma

BackgroundSurgery for perihilar cholangiocarcinoma (pCCA) is associated with high morbidity and mortality rates. The impact of surgery for pCCA may affect patients after discharge. The aim of this study was to investigate all morbidity and mortality during the first year after surgery for pCCA.MethodsAll consecutive liver resections for suspected pCCA between 2000 and 2019 at two tertiary referral centers were included. All morbidity and mortality until one year after surgery was collected retrospectively, including readmissions and reinterventions. All recurrences within the first year were scored to calculate disease-free survival.ResultsIn 250 patients, the major morbidity rate was 61% (152/250), in-hospital mortality was 15% (37/250) and 90-day mortality was 16% (40/250). In the 213 discharged patients, 98 patients (46%) suffered 260 surgical complications. These complications required 185 readmissions in 92 patients (43%) and 400 reinterventions in 110 patients (52%), including 330 radiological (83%), 61 endoscopic (15%) and 9 surgical reinterventions (2%). One-year overall survival was 77% and one-year disease-free survival was 70%. Out of the 20 patients who died within the first year after discharge, 15 died of recurrent disease and 3 due to surgery related complications and 2 of unknown causes.ConclusionReadmissions, reinterventions and complications are frequent throughout the first year after surgery for pCCA in tertiary referral hospitals. These adverse events warrants treatment of these complex patients in high expertise centers offering intensive perioperative care and close follow-up of patients after discharge.     

Imaging and surgical planning for perihilar cholangiocarcinoma

Recent advances in multidetector computed tomography (MDCT) offer several benefits for management of perihilar tumors. Resection planning for perihilar cholangiocarcinoma should consider two factors: safety and curability. Recognition of individual anatomic variations is particularly important for avoiding intraoperative injury. In particular, hepatic arterial variations often restrict resection procedures. Extent of both longitudinal and vertical invasion by biliary tumors can be estimated from multiplanar reconstruction (MPR) images. Longitudinal extent of resection can be planned based on two anatomic landmarks, the U point and the P point, readily identifiable in preoperative 3‐dimensional (3D) images and by intraoperative inspection. Concerning vertical invasion, when direct vascular invasion is suspected from a finding of attachment of tumor and vessels such as portal veins and/or hepatic arteries without a thin low‐density plane of separation shown by MPR, these vessels should be resected en bloc with the tumor. Surgical team members can plan and simulate details of vascular resection and reconstruction using 3D images. Reduced operative morbidity and increased R0 resection rates are expected because of better planning of procedures. These techniques soon may increase long‐term survival for patients with perihilar cholangiocarcinoma.     

Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases

BackgroundThe aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.MethodsConsecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.ResultsIn the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97–2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09–2.69) were independent poor prognostic factors in the resected cohort.ConclusionPatients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.     

Single-center experience of liver transplantation for perihilar cholangiocarcinoma

BackgroundTraditionally, curative resection was considered the cornerstone of treatment for perihilar cholangiocarcinoma. More recently, liver transplantation (LT) offered an alternative for patients with unresectable disease. The purpose of this study was to assess our experience with perihilar cholangiocarcinoma and LT.MethodsA perihilar cholangiocarcinoma protocol was commenced in 2006 whereby diagnosed patients were enrolled onto an institutional registry for LT consideration. Data on patient progression and oncologic outcomes were assessed.ResultsFifty-eight patients were initially enrolled onto the protocol and 38 proceeded to LT following neoadjuvant chemoradiation (mean age 55.6 ± 11.4 years). Mean time to LT was 3.7 ± 2 months and, among those transplanted, 14 (37%) had underlying primary sclerosing cholangitis (PSC). Thirteen (34%) patients developed malignant recurrence and there were no differences in disease recurrence between PSC (n = 3) and non-PSC (n = 10) patients (p = 0.32). Overall patient survival was 91%, 58% and 52% at 1-, 3- and 5-years corresponding with 81%, 52% and 46% graft survival, respectively.ConclusionRigorous patient selection and chemoradiation treatment algorithms can be highly effective in treating perihilar cholangiocarcinoma. For appropriately selected candidates, LT can provide a 52% 5-year survival for patients who would otherwise have no surgical treatment option.     

Conditional survival in patients with unresectable perihilar cholangiocarcinoma

Background

Conditional survival is the life expectancy from a point in time for a patient who has survived a specific period after presentation.The aim of the study was to estimate conditional survival for patients with unresectable perihilar cholangiocarcinoma.

Indications for portal vein embolization in perihilar cholangiocarcinoma

Preoperative portal vein embolization (PVE) is often performed as a routine procedure before extended hepatectomy to minimize postoperative liver failure. However, the indications for PVE in perihilar cholangiocarcinoma (PCCA), which differ between institutions, remain controversial. In the present study, we examined the indications for PVE in patients with PCCA. A comprehensive meta‐analysis of PVE was performed using the PubMed, Medline, and Cochrane databases. The present study, which included 3033 patients (45 publications), compared the results of 836 cases in the PCCA group and 2197 cases in the other hepatic tumor (OHT) group. In the PCCA group, percent future remnant liver (%FRL) and ratio of %FRL to indocyanine green (ICG) were used as criteria in 71% and 25% of cases, respectively, and a %FRL < 40% was used as indication for PVE in 90% of cases. The rates of resection of the bile duct, simultaneous pancreaticoduodenectomy, and reconstruction of the portal vein and hepatic artery were high in the PCCA group (P < 0.001). Mortality after hepatectomy was 3.7% in the PCCA group and 1.9% in the OHT group (P < 0.001). The indication for PVE in PCCA patients is %FRL < 40% in many institutions. The indications for PVE in PCCA patients should be distinguished from those in other hepatic tumors because of the complex surgery required for PCCA.     

The prognostic role of tumor-associated unilateral portal vein occlusion in perihilar cholangiocarcinoma

BackgroundWhile a certain degree of tumor infiltration of the portal vein is common in patients with perihilar cholangiocarcinoma (pCCA) scheduled for surgery, complete tumor-associated portal vein occlusion (PVO) is less frequently observed. Here, we analyzed the impact of PVO on perioperative and oncological outcomes in pCCA patients.MethodsBetween 2010 and 2019, 127 patients with pCCA underwent surgery in curative intent at our department of which 17.3% (22/127) presented with PVO. Extensive group comparisons were conducted and the association of cancer-specific (CSS) and disease-free survival (DFS) with PVO and other clinico-pathological characteristics were assessed using Cox regression models.ResultsPatients without PVO showed a median CSS of 65 months (3-year-CSS = 64%, 5-year-CSS = 53%) compared to 31 months (3-year-CSS = 43%, 5-year-CSS = 17%) in patients with PVO (p = 0.025 log rank). Patients with PVO did also display significant perioperative mortality (22.7%, 5/22) compared to patients without PVO (14.3%, 15/105, p = 0.323). Further, PVO (CSS: HR = 5.25, p = 0.001; DFS: HR = 5.53, p = 0.001) was identified as independent predictors of oncological outcome.ConclusionsPVO has been identified as an important prognostic marker playing a role in inferior oncological outcome in patients with pCCA. As PVO is also associated with notable perioperative mortality, surgical therapy should be considered carefully in pCCA patients.     

Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma

Cholangiocarcinoma(CCC) is the most aggressive malignant tumor of the biliary tract. Perihilar CCC(pCCC) is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results. Besides its clinical presentation, a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis. Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure. During staging iter, magnetic resonance can obtain satisfactory cholangiographic images, while invasive techniques should be used if bile duct samples are needed. Consistently, to improve diagnostic potential, bile duct drainage is not necessary in jaundice, while it is indicated in refractory cholangitis or when liver hypertrophy is needed. Once resecability criteria are identified, the extent of liver resection is secondary to the longitudinal spread of CCC. While in the past type IV pCCC was not considered resectable, some authors reported good results after their treatment. Conversely, in selected unresectable cases, liver transplantation could be a valuable option. Adjuvant chemotherapy is the standard of care for resected patients, while neoadjuvant approach has growing evidences. If curative resection is not achieved, radiotherapy can be added to chemotherapy. This multistep curative iter must be carried on in specialized centers. Hence, the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.     

Cystic micropapillary neoplasm of peribiliary glands with concomitant perihilar cholangiocarcinoma

We report a case of a 75-year-old man with cystic micropapillary neoplasm of peribiliary glands detected preoperatively by radiologic examination. Enhanced computed tomography showed a low-density mass 2.2 cm in diameter in the right hepatic hilum and a cystic lesion around the common hepatic duct. cholangiocarcinoma, right hepatectomy with caudate lobectomy and bile duct resection were performed. Pathological examination revealed perihilar cholangiocarcinoma mainly involving the right hepatic duct. The cystic lesion was multilocular and covered by columnar lining epithelia exhibiting increased proliferative activity and p53 nuclear expression; it also contained foci of micropapillary and glandular proliferation. Therefore, the lesion was diagnosed as a cystic micropapillary neoplasm of peribiliary glands and resembled flat branch-type intraductal papillary mucinous neoplasm of the pancreas. Histological examination showed the lesion was discontinuous with the perihilar cholangiocarcinoma. Immunohistochemistry showed the cystic neoplasm was strongly positive for MUC6 and that the cholangiocarcinoma was strongly positive for MUC5 AC and S100 P. These results suggest these two lesions have different origins. This case warrants further study on whether this type of neoplasm is associated with concomitant cholangiocarcinoma as observed in pancreatic intraductal papillary mucinous neoplasm with concomitant pancreatic duct adenocarcinoma.     

Progress in diagnosis and surgical treatment of perihilar cholangiocarcinoma

Cholangiocarcinomas are heterogeneous biliary tract tumors that cause devastating disease. Perihilar cholangiocarcinoma (PHC) is the most common type of biliary tract cancer and are associated with a high mortality. Diagnoses of PHC depend on the results of its clinical presentation, serum biomarkers and imaging techniques. Pre-operative managements including pre-operative biliary drainage (PBD) and portal vein embolization (PVE) could reduce mortality. The best chance of long-term survival and potential cure is surgical resection with negative surgical margin. Lymph node metastasis over N2 nodes precludes long-term survival. The benefit of concomitant vascular resection remains uncertain. Liver transplantation combined with neoadjuvant chemotherapy with radiotherapy is a promising option in highly selected patients with unresectable tumors. Herein, an overview is provided of developments in diagnosis, peri-operative management and surgical treatment among patients with PHCs.     

Management of perihilar cholangiocarcinoma in the era of multimodal therapy

Perihilar cholangiocarcinoma (CCA) is the second most common primary malignant tumor of the liver. In the USA, there are approximately 3000 cases of CCA diagnosed annually, with approximately 50–70% of these tumors arising at the hilar plate of the biliary tree. Risk factors include advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, parasitic infection, inflammatory bowel disease, cirrhosis and chronic pancreatitis. Patients typically present with jaundice, abdominal pain, pruritus and weight loss. The mainstays of treatment include surgery, chemotherapy, radiation therapy and photodynamic therapy. Specific preoperative interventions for patients with perihilar CCA include endoscopic retrograde cholangiopancreatography, percutanteous transhepatic cholangiography and portal vein embolization. Surgical resection offers the only chance for curative therapy in perihilar CCA. R0 resection is of utmost importance and has been linked to improved survival. Major hepatic resection is needed to achieve both longitudinal and radial margins negative for tumor. Fractionated stereotactic body radiotherapy has shown promising results in CCA. Perihilar CCA typically presents with advanced disease, and many patients receive systemic therapy; however, the response to current regimens is limited. Orthotopic liver transplantation offers complete resection of locally advanced tumors in select patient groups.     

Outcomes of left trisectionectomy and right hepatectomy for perihilar cholangiocarcinoma

Background

Right hepatectomy (RH) is the standard surgical procedure for perihilar cholangiocarcinoma (PHC) with right-sided predominance in many centers. Although left trisectionectomy (LT) is aggressively performed for PHC with left-sided predominance in high-volume centers, the surgical and survival outcomes of LT are unclear. Therefore, this study aimed to compare the outcomes of LT and RH for PHC.

Surgical management of perihilar cholangiocarcinoma: a Khon Kaen experience

Cholangiocarcinoma is the most common cancer in the northeast of Thailand. Most of the patients present when the disease is in an advanced stage. Improvement of preoperative diagnoses and surgical techniques provide more satisfactory results. Herein we reviewed our 30‐year experience in management of perihilar cholangiocarcinoma in Khon Kaen northeast Thailand. Between 1982 and 2012 we reviewed four specific studies of perihilar cholangiocarcinoma in Srinagarind Hospital, Khon Kaen, Thailand. The first study focused on advanced surgical pathology and palliative surgery, which were used to treat obstructive jaundice cholangiocarcinoma patients. Long‐term survival in this study was rare with a one‐year survival of just 15%. The second study was conducted on 30 consecutive cases of perihilar cholangiocarcinoma who presented with obstructive jaundice without preoperative biliary drainage. All the patients underwent major liver resection with bilio‐enteric reconstruction. Perioperative mortality was 6.7% without a 5‐year survival. The third study aimed to analyze the survival rates and factors affecting survival in extrahepatic CCA patients following surgical treatment at Srinagarind Hospital and concluded that resection margins are an important prognostic factor. The last study objective was the analysis of curative surgical attempt in 99 consecutive perihilar cholangiocarcinoma and results showed that R0 resection could improve long‐term survival. We evaluated four studies of perihilar cholangiocarcinoma in Srinagarind Hospital, Khon Kaen, Thailand from 1982–2012. Viewed chronologically there has been a progressive improvement of diagnosis and surgical treatment during the past 30 years. Despite these advances the 5‐year survival rate remains unsatisfactorily low. Future improvement of patient selection and surgical techniques can lead to a greater survival rate for patients.     

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

AIM To clarify the role of neoadjuvant concurrent chemoradiotherapy(NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma(CCA).METHODS We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows:(1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or(2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS The median disease-free survival(DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were26.0 and 15.1 mo, respectively(P = 0.91). The median overall survival(OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively(P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis(P = 0.01). CONCLUSION NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.