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.     

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。     

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.     

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.     

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.     

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.     

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.     

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.

New staging system and a registry for perihilar cholangiocarcinoma

Perihilar cholangiocarcinoma is one of the most challenging diseases with poor overall survival. The major problem for anyone trying to convincingly compare studies among centers or over time is the lack of a reliable staging system. The most commonly used system is the Bismuth-Corlette classification of bile duct involvement, which, however, does not include crucial information such as vascular encasement and distant metastases. Other systems are rarely used because they do not provide several key pieces of information guiding therapy. Therefore, we have designed a new system reporting the size of the tumor, the extent of the disease in the biliary system, the involvement of the hepatic artery and portal vein, the involvement of lymph nodes, distant metastases, and the volume of the putative remnant liver after resection. The aim of this system is the standardization of the reporting of perihilar cholangiocarcinoma so that relevant information regarding resectability, indications for liver transplantation, and prognosis can be provided. With this tool, we have created a new registry enabling every center to prospectively enter data on their patients with hilar cholangiocarcinoma (www.cholangioca.org). The availability of such standardized and multicenter data will enable us to identify the critical criteria guiding therapy.     

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.     

Preoperative combined radiotherapy and chemotherapy for rectal cancer does not affect early postoperative morbidity and mortality in low anterior resection

PURPOSE: It is not yet known whether preoperative combined radiotherapy and chemotherapy for rectal cancer affects postoperative mortality and morbidity. We therefore evaluated early postoperative complications in patients given adjuvant radiotherapy and chemotherapy before surgery for middle and lower rectal adenocarcinoma. METHODS: Between 1994 and 1998, 41 patients underwent combined preoperative pelvic radiotherapy and chemotherapy at our institution. Most of the patients had 45 Gy (1.8 Gy/day/25 fractions) during five weeks plus 5-fluorouracil (350 mg/m²/day) and low-dose leucovorin (10 mg/m²/day) bolus on Days 1 to 5 and 29 to 33. Surgery was performed four to six weeks after completion of adjuvant therapy. The 41 patients (Group A) were retrospectively compared with 30 patients (Group B) who, in the same period, underwent surgery without preoperative adjuvant therapy. The groups were homogeneous for age, gender, preoperative risk factors, operating surgeon, and pathologic stage. Mean distance of the tumor from the anal verge was shorter in Group A patients (P=0.031). RESULTS: There were seven major postoperative complications in each group. No significant differences were found between the groups for morbidity and mortality rates. Considering all patients, more postoperative complications were found in patients scored as American Society of Anesthesiologists 3, in those with a preoperative hemoglobin value <10 g/dl, and in those without a diverting stoma (P=0.0048,P=0.0453, andP=0.0033, respectively). At multivariate analysis, independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 343;P=0.022), diverting stoma (relative risk, 159;P=0.010), type of surgical procedure (relative risk, 38.9;P=0.048), preoperative hemoglobin value (relative risk, 9.72;P=0.061), and intraoperative blood loss (relative risk, 1;P=0.027). In Group A patients, the absence of diverting stomas was associated with major postoperative complications (P=0.0307), and independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 56;P=0.111) and absence of a diverting stoma (relative risk, 22.42;P=0.222). CONCLUSION: Early postoperative complications after resection for middle and lower rectal adenocarcinoma are affected by intraoperative and preoperative risk factors and absence of diverting stomas, but not by preoperative adjuvant therapy.     

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.