Combining E-PASS model and disease specific risk factors to predict severe morbidity after liver and bile duct resection for perihilar cholangiocarcinoma

BackgroundEstimation of physiologic ability and surgical stress system (E-PASS) has been shown to be effective in predicting morbidity after surgery for perihilar cholangiocarcinoma (PHCC). Nevertheless, E-PASS does not include an assessment of the disease specific risk factors. The aim of the study was to estimate the combined impact of E-PASS and specific preoperative factors on major morbidity for PHCC patients.MethodsA retrospective analysis of a prospectively collected data was performed. Severe morbidity according to complication comprehensive index was defined as ≥40 points. A value of comprehensive risk score (CRS) ≥1 was taken as critical.ResultsMultivariate analysis of perioperative data from 122 patients revealed significant impact of five factors (CRS ≥1, future liver remnant volume <50%, T4 stage, moderate and severe cholangitis, INR) on the risk of severe morbidity after resection. The AUC for the combination of these factors was classified as good predictive value (0.810, 95% CI 0.729–0.891) and poor predictive value (0.673, 95% CI 0.573–0.773) for CRS alone (p = 0.040).ConclusionA combination of E-PASS with disease specific risk factors is a reliable predictive model for major morbidity for patients undergoing radical surgery for PHCC.     

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.     

Left- versus right-sided hepatectomy with hilar en-bloc resection in perihilar cholangiocarcinoma

BackgroundMajor liver resections with portal vein resection (PVR) have emerged as the preferred treatment for patients with perihilar cholangiocarcinoma (pCCA). Whether the resection of the liver should be preferably performed as left- (LH) or right-sided hepatectomy (RH) with or without hilar en-bloc technique is still subject of ongoing debate.MethodsBetween 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. Perioperative, pathological and survival data from all consecutive patients undergoing hilar en-bloc resection for pCCA were analyzed retrospectively. Patients undergoing hepatoduodenectomy (n = 8) or ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) (n = 2) were excluded from the analysis.ResultsTumor grading, microvascular invasion, lymphovascular invasion, N-category, T-category, R-status and UICC-tumor staging were similar in the RH (n = 45) and LH (n = 36) groups. Perioperative morbidity and mortality were higher after RH compared to LH (mortality: 15.6% (7/45) vs. 8.3% (3/36) p = 0.003). Three-year (62% vs. 51%) and the 5-year OS (30% vs. 46%) were comparable between LH and RH groups respectively (p = 0.519, log rank).ConclusionsThe present study supports the concept of surgically aggressive therapy in pCCA. LH and RH hilar en-bloc resection demonstrate a comparable long-term survival, suggesting that LH hilar en-bloc resections are feasible and safe in high-volume centers.     

The morbidity, mortality, and prognostic factors for ampullary carcinoma and distal cholangiocarcinoma

BACKGROUND/AIMS: Ampullary carcinoma and distal cholangiocarcinoma are potentially more amenable to pancreaticoduodenectomy for long-term survival than pancreatic carcinoma. The aims of this study are to evaluate experience with ampullary carcinoma and distal cholangiocarcinoma at a single institution. METHODOLOGY: Seventy-two consecutive patients with ampullary carcinoma and distal cholangiocarcinoma who underwent radical resection at Chiba University Hospital from 1985 to 2001. Clinicopathological factors for survival were evaluated by univariate and multivariate analyses in a retrospective study. RESULTS: Pancreaticoduodenectomy was performed in 37 of 38 patients for ampullary carcinoma and 29 of 34 patients for distal cholangiocarcinoma. The morbidity rates of patients with ampullary carcinoma and distal cholangiocarcinoma were 21.1% and 20.6%, and mortality rates were 0% and 2.9%, respectively. The cumulative 5-year survival rates in cases of ampullary carcinoma and distal cholangiocarcinoma were 63% and 45%, respectively. By univariate analysis, pancreatic invasion, lymph node metastasis, and duodenal invasion were significant prognostic factors for ampullary carcinoma. Perineural invasion and histological grade, but not lymph node metastasis, were significant factors for distal cholangiocarcinoma. Multivariate analysis indicated that lymph node metastasis was the only independent prognostic factor for ampullary carcinoma, and that perineural invasion was the only independent prognostic factor for distal cholangiocarcinoma. CONCLUSIONS: The overall mortality of 1.4% and the cumulative 5-year survival rates for ampullary carcinoma and distal cholangiocarcinoma are acceptable. Ampullary carcinoma with lymph node metastasis and distal cholangiocarcinoma with perineural invasion have higher risk of recurrence.     

改良外科Apgar评分对肝门部胆管癌术后并发症的预测价值

目的探讨改良外科Apgar评分(mSAS)对肝门部胆管癌术后并发症的预测能力。方法回顾性分析2013年4月-2019年9月于中国医科大学附属盛京医院因肝门部胆管癌手术的患者188例,分为有并发症组(n=125)和无并发症组(n=63)。比较两组患者的临床资料,包括性别、年龄、CEA、CA19-9、Bismuth-Corlett分型、术前黄疸及Alb水平、外科Apgar评分(SAS)、手术方式等。偏态分布的计量资料两组间比较采用非参数Mann-Whitney U检验。计数资料两组间比较采用χ2检验。多因素分析采用logistic回归模型,并绘制受试者工作特征曲线(ROC曲线)。ROC曲线下面积(AUC)的比较采用Z检验。结果188例患者中125例术后出现了并发症,发生率为66.5%。并发症组与无并发症组间mSAS差异具有统计学意义(χ2=65.685,P<0.001)。mSAS高分组(n=101)术后并发症发生率为40.6%,而mSAS低分组(n=87)术后并发症发生率为96.6%;对并发症进一步分析显示,菌血症、肺部感染、腹腔感染、切口并发症、腹腔出血以及肝衰竭在两组间差异有统计学意义(χ2值分别为15.196、52.245、48.409、5.556、11.087、17.772,P值均<0.05)。多因素回归分析显示,mSAS[优势比(OR)=0.026,95%可信区间(95%CI:0.007~0.099,P<0.001)、手术方式(OR=2.195,95%CI:1.070~4.500,P=0.032)、术前黄疸水平(OR=2.470,95%CI:1.376~4.434,P=0.002)]是影响肝门部胆管癌术后并发症发生的独立因素。mSAS与SAS预测肝门部胆管癌术后出现并发症的AUC分别为0.830(95%CI:0.768~0.880)和0.776(95%CI:0.710~0.834)。mSAS的最佳临界值为6.5,敏感度为96.6%,特异度为59.4%,准确度为76.6%。结论mSAS有助于预测肝门部胆管癌术后并发症的发生。     

Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review

Background: Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase Ⅱ studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA.Data sources: A systematic review of the literature for reports of patients undergoing resection of PH- CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings hilar cholangiocarcinoma, Klatskin, chemoradiotherapy and chemotherapy were used. Data were extracted on demographic profile, dis- ease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. Results: There were seven reports on this topic, with median recruitment period of 14 (range 4–31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9–28) months and 5-year survival 20%. Conclusions: There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.     

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.     

Outcome of surgical treatment of hilar cholangiocarcinoma: a special reference to postoperative morbidity and mortality

Background/purpose

Radical resection for hilar cholangiocarcinoma is still associated with significant morbidity and mortality. The aim of this study was to analyze short-term surgical outcomes and to validate our strategies, including preoperative management and selection of operative procedure.

Methods

We surgically treated 146 consecutive patients with hilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization, and selection of operative procedure based on tumor extension and hepatic reserve. Major hepatectomy was conducted in 126 patients, and caudate lobectomy or hilar bile duct resection in 20 patients.

Results

The overall 5-year survival rate was 35.5%, with overall in-hospital mortality and morbidity rates of 3.4 and 44%, respectively. Hyperbilirubinemia (total bilirubin >5 mg/dL, persisted for >7 postoperative days) and liver abscess were the most frequent complications. Five among 9 patients with liver failure (total bilirubin >10 mg/dL) encountered in-hospital mortality. Four out of 5 mortality patients had suffered circulatory impairment of the remnant liver due to other complications. Multivariate analysis revealed that operative time is a single independent significant predictive factor (odds ratio, 1.005; 95% confidence interval, 1.000–1.010, P = 0.04) for postoperative complications.

Conclusions

Aggressive resection for hilar cholangiocarcinoma, performed in accordance with strict management strategy, achieved acceptably low mortality. Prolonged operative time was a risk for morbidity following hepatobiliary resection.     

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.     

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.     

Preoperative computed tomography assessment of skeletal muscle mass is valuable in predicting outcomes following hepatectomy for perihilar cholangiocarcinoma

Background

Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with high rates of morbidity and mortality.

Objectives

This study investigated the impact of low skeletal muscle mass on short- and longterm outcomes following hepatectomy for PHC.

Methods

Patients included underwent liver surgery for PHC between 1998 and 2013. Total skeletal muscle mass was measured at the level of the third lumbar vertebra using available preoperative computed tomography images. Sex-specific cut-offs for low skeletal muscle mass were determined by optimal stratification.

Results

In 100 patients, low skeletal muscle mass was present in 42 (42.0%) subjects. The rate of postoperative complications (Clavien–Dindo Grade III and higher) was greater in patients with low skeletal muscle mass (66.7% versus 48.3%; multivariable adjusted P = 0.070). Incidences of sepsis (28.6% versus 5.2%) and liver failure (35.7% versus 15.5%) were increased in patients with low skeletal muscle mass. In addition, 90-day mortality was associated with low skeletal muscle mass in univariate analysis (28.6% versus 8.6%; P = 0.009). Median overall survival was shorter in patients with low muscle mass (22.8 months versus 47.5 months; P = 0.014). On multivariable analysis, low skeletal muscle mass remained a significant prognostic factor (hazard ratio 2.02; P = 0.020).

Conclusions

Low skeletal muscle mass has a negative impact on postoperative mortality and overall survival following resection of PHC and should therefore be considered in preoperative risk assessment.     

Post-operative morbidity results in decreased long-term survival after resection for hilar cholangiocarcinoma

Background

The purpose of the present study was to demonstrate that post-operative morbidity (PM) associated with resections of hilar cholangiocarcinoma (HCCA) is associated with short- and long-term patient survival.

Methods

Between 1998 and 2008, 51 patients with a median age of 64 years underwent resection for HCCA at a single institution. Associations between survival and clinicopathologic factors, including peri- and post-operative variables, were studied using univariate and multivariate models.

Results

Seventy-six per cent of patients underwent major hepatectomy with resection of the extrahepatic bile ducts. The 30- and 90-day operative mortality was 10% and 12%. The overall incidence of PM was 69%, with 68% of all PM as major (Clavien grades III–V). No difference in operative blood loss or peri-operative transfusion rates was observed for patients with major vs. minor or no PM. Patients with major PM received adjuvant chemotherapy less frequently than patients with minor or no complications 29% vs. 52%, P= 0.15. The 1-, 3- and 5-year overall (OS) and disease-specific survival (DSS) rates for all patients were 65%, 36%, 29% and 77%, 46%, 35%, respectively. Using univariate and multivariate analysis, margin status (27% R1), nodal metastasis (35% N1) and major PM were associated with OS and DSS, P < 0.01. Major PM was an independent factor associated with decreased OS and DSS [hazard ratio (HR) = 3.6 and 2.8, respectively, P < 0.05]. The median DSS for patients with major PM was 14 months compared with 40 months for patients who experienced minor or no PM, P < 0.01.

Conclusion

Extensive operations for HCCA can produce substantial post-operative morbidity. In addition to causing early mortality, major post-operative complications are associated with decreased long-term cancer-specific survival after resection of HCCA.     

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.