Mechteld C. de Jong

Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: An international multi-institutional analysis of 1669 patients

Objective(s):To investigate rates and patterns of recurrence in patients following curative intent surgery for colorectal liver metastasis. Background:Outcomes following surgical management of colorectal liver metastasis have largely focused on overall survival. Contemporary data on rates and patterns of recurrence following surgery for colorectal liver metastasis are limited. Methods:One thousand six hundred sixty-nine patients treated with surgery (resection ± radiofrequency ablation [RFA]) for colorectal liver metastasis between 1982 and 2008 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results:At the time of the initial liver-directed surgery, surgical treatment was resection only (90.2%), resection plus RFA (8.0%), or RFA alone (1.8%). While 5-year overall survival was 47.3%, 947 (56.7%) patients recurred with a median RFS time of 16.3 months. First recurrence site was intrahepatic only (43.2%), extrahepatic only (35.8%), intra- and extrahepatic (21.0%). There was no difference in RFS based on site of recurrence (intrahepatic: 16.9 months; extrahepatic: 16.6 months; intra- and extrahepatic: 16.2 month; P > 0.05). Receipt of adjuvant chemotherapy was associated with overall recurrence risk (hazard ratio [HR] = 0.56), while history of RFA (HR = 2.39, P = 0.001) and R1 margin status (HR = 1.36) were predictive of intrahepatic recurrence. Pattern of recurrence and RFS remained similar following repeat surgery for recurrent disease. Conclusions:While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years. The pattern of failure is distributed relatively equally among intrahepatic, extrahepatic, and intra- plus extrahepatic sites. Patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.

Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis of Prognostic Factors and Lymph Node Assessment

PURPOSE To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. PATIENTS AND METHODS From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. RESULTS Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). CONCLUSION Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.

Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis

BACKGROUND As indications for liver resection expand, objective measures to assess the risk of peri-operative morbidity are needed. The impact of sarcopenia on patients undergoing liver resection for colorectal liver metastasis (CRLM) was investigated. METHODS Sarcopenia was assessed in 259 patients undergoing liver resection for CRLM by measuring total psoas area (TPA) on computed tomography (CT). The impact of sarcopenia was assessed after controlling for clinicopathological factors using multivariate modelling. RESULTS Median patient age was 58 years and most patients (60%) were male. Forty-one (16%) patients had sarcopenia (TPA ≤ 500 mm(2) /m(2) ). Post-operatively, 60 patients had a complication for an overall morbidity of 23%; 26 patients (10%) had a major complication (Clavien grade ≥3). The presence of sarcopenia was strongly associated with an increased risk of major post-operative complications [odds ratio (OR) 3.33; P= 0.008]. Patients with sarcopenia had longer hospital stays (6.6 vs. 5.4 days; P= 0.03) and a higher chance of an extended intensive care unit (ICU) stay (>2 days; P= 0.004). On multivariate analysis, sarcopenia remained independently associated with an increased risk of post-operative complications (OR 3.12; P= 0.02). Sarcopenia was not significantly associated with recurrence-free [hazard ratio (HR) = 1.07] or overall (HR = 1.05) survival (both P > 0.05). CONCLUSIONS Sarcopenia impacts short-, but not long-term outcomes after resection of CRLM. While patients with sarcopenia are at an increased risk of post-operative morbidity and longer hospital stay, long-term survival is not impacted by the presence of sarcopenia.

Conditional Survival after Surgical Resection of Colorectal Liver Metastasis: An International Multi-Institutional Analysis of 949 Patients

BACKGROUND Traditionally, survival estimates have been reported solely as survival from the time of surgery, but future survival probability likely changes based on the survival time already accumulated after therapy-otherwise known as conditional survival (CS). We sought to assess the comparative performance of various colorectal liver metastasis prognostic scoring systems, as well as to investigate the CS of patients who underwent resection of colorectal liver metastasis. STUDY DESIGN Between 1982 and 2008, 949 patients who underwent colorectal liver metastasis resection were identified from an international multi-institutional database. Various prognostic scoring systems were evaluated using Cox proportional hazards models and calculated concordance index (c). CS estimates were calculated as CS = S((x+5))/S((x)). RESULTS Overall survival after liver resection was 65% at 3 years and 45% at 5 years, with a median survival of 52 months. All of the prognostic scoring systems had poor-to-moderate prognostic discriminatory ability (Fong c = 0.57, Nordlinger c = 0.56, Memorial Sloan-Kettering Cancer Center nomogram c = 0.58). Using CS, the probability of surviving an additional 5 years, given that the patient had already survived 1, 3, or 5 years, was 41%, 40%, or 50%, respectively. The inadequate performance of the prognostic scoring systems was explained by the fact that as survival from liver resection increased from 0 to 5 years, the 5-year observed CS improved substantially for patients who were initially predicted to have poor survival at the time of surgery. CONCLUSIONS Colorectal liver metastasis prognostic scoring systems have fair-to-moderate performance. CS can provide more accurate prognostic information for patients and physicians after colorectal liver metastasis resection and should be incorporated into the quantification of survival.

The impact of portal vein resection on outcomes for hilar cholangiocarcinoma: a multi-institutional analysis of 305 cases.

BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes hepatectomy, but the role of portal vein resection (PVR) remains controversial. In this study, the authors sought to identify factors associated with outcome after surgical management of hilar cholangiocarcinoma and examined the impact of PVR on survival.

Hepatectomy for Noncolorectal Non-Neuroendocrine Metastatic Cancer: A Multi-Institutional Analysis

BACKGROUND Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases. STUDY DESIGN A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. RESULTS There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003). CONCLUSIONS Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined.

Disappearing colorectal liver metastases after chemotherapy: should we be concerned?

BackgroundWith increasing efficacy of preoperative chemotherapy for colorectal cancer, more patients will present with one or more disappearing liver metastases (DLM) on preoperative cross-sectional imaging.Patients and MethodsA retrospective review was conducted evaluating the radiological response to preoperative chemotherapy for 168 patients undergoing surgical therapy for colorectal liver metastases at Johns Hopkins Hospital between 2000 and 2008.ResultsForty patients (23.8%) had one or more DLM, accounting for a total of 127 lesions. In 22 patients (55%), all DLM sites were treated during surgery. Of the 17 patients with unidentified, untreated DLM, ten patients (59%) developed a local recurrence at the initial site, half of which also developed recurrences in other sites. While the intrahepatic recurrence rate was higher for patients with DLM left in situ (p = 0.04), the 1-, 3-, and 5-year overall survival rate was not significantly different for patients with DLM left in situ (93.8%, 63.5%, and 63.5%, respectively) when compared to patients with a radiological chemotherapy response in whom all original disease sites were surgically treated (92.3%, 70.8%, and 46.2%, respectively; p = 0.66).ConclusionsDLM were frequently observed in patients undergoing preoperative chemotherapy for liver metastases. Survival was comparable in patients with untreated DLM, in spite of high intrahepatic recurrence rates seen in these patients. Therefore, aggressive surgical therapy should be considered in patients with marked response to chemotherapy, even when all DLM sites cannot be identified.

Two-stage strategy for patients with extensive bilateral colorectal liver metastases.

BACKGROUND Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases. The present study assesses the feasibility and outcome of two-stage hepatectomy for the treatment of colorectal liver metastases. METHODS From January 1994 to December 2008, 720 patients underwent liver resections at two institutions for colorectal liver metastases. The feasibility and outcomes of two-staged hepatectomies were evaluated. RESULTS Forty-five patients were eligible for the two-stage approach and both stages were completed in 35 patients (78%). Reasons for failure included disease progression (n= 7), poor performance status (n= 1) and death after the first stage (n= 2). Patients who completed both stages had significantly fewer lesions than patients who failed to complete the second stage (5 vs. 8; P= 0.02). No differences between the two groups were observed with regard to lesion size, receipt of radiofrequency ablation (RFA) or presence of extrahepatic disease. Post-operative morbidity (24% vs. 26%; P= 0.9) and mortality (4% vs. 5%; P= 0.8) was similar between the first and second stages. Median overall survival was 16 months. Three-year survival was significantly worse for patients failing to complete both stages (18%) compared with patients completing both stages (58%) (P < 0.001). Similar survival rates were observed between patients who completed two-stage vs. patients treated with a planned single-stage hepatectomy (58% vs. 53%; P= 0.34). CONCLUSION The two-stage strategy for colorectal liver metastases can be performed with acceptable morbidity and mortality. The second stage will not be feasible in 20-25% of patients. Patients who are able to complete the two-stage approach, however, may have long-term survival comparable to patients treated with a planned single-stage hepatectomy.

Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: A dual-center analysis

Objectives:To analyze the perioperative and long-term outcomes of patients undergoing liver-directed therapy after pancreaticoduodenectomy in a large dual-center cohort of patients. Background:Although aggressive liver-directed therapy may be beneficial, liver-directed therapy may be associated with a high risk of complications after pancreaticoduodenectomy. Methods:Of 5025 patients who underwent pancreaticoduodenectomy at the Johns Hopkins Hospital and the Mayo Clinic between 1970 and 2008, 126 (2.5%), patients were identified who were also treated with either simultaneous or staged liver-directed therapy. Data on demographics, primary tumor, and hepatic metastasis characteristics, as well as details of the liver-directed therapy were collected and analyzed. Results:Primary tumor histology included neuroendocrine carcinoma (34.9%), pancreatic ductal adenocarcinoma (33.4%), distal cholangiocarcinoma (8.7%), ampullary carcinoma (7.1%), duodenal carcinoma (4.0%), or other (11.9%). Liver-directed therapies included hepatic resection alone (45.2%), hepatic resection plus ablation (11.1%), ablation alone (7.9%), transarterial chemoembolization (9.5%), and whole-liver irradiation (22.2%). The overall morbidity following liver-directed therapy was 34.1% and overall mortality was 2.4%. Patients undergoing staged liver-directed therapy (14.5%) versus simultaneous pancreaticoduodenectomy plus liver-directed therapy (7.0%) were more likely to develop a liver abscess (P < 0.05). Of those patients who developed complications, the majority (55.8%) were major (Clavien grade ≥3). Conclusions:Pancreaticoduodenectomy plus liver-directed therapy is associated with considerable morbidity. The incidence of hepatic abscess is increased in patients undergoing staged pancreaticoduodenectomy followed by liver-directed therapy.

Safety and efficacy of curative intent surgery for peri-ampullary liver metastasis

The management of patients with peri‐ampullary liver metastasis remains controversial. We sought to assess the safety and efficacy of curative intent surgery for peri‐ampullary liver metastasis.