Ana L. Gleisner

Simultaneous resections of colorectal cancer and synchronous liver metastases: A multi-institutional analysis

BackgroundThe safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections.MethodsClinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985–2006 were reviewed.Results610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (≥ three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008].ConclusionsSimultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific.

Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: Implications for transplant eligibility

Objective:To examine the diagnostic agreement of preoperative needle core biopsy (NCB) grading of hepatocellular carcinoma (HCC) compared with the final surgical pathologic tumor grade. Summary Background Data:Some centers have adopted protocols for selecting patients with HCC for transplantation based on tumor grade as determined by preoperative NCB. The validity of NCB to predict final tumor grade has not been previously assessed. Methods:A total of 211 patients who underwent hepatic resection, open radiofrequency, or transplantation for HCC between 1998 and 2004 were identified. Clinicopathologic, NCB, and surgical data were collected and analyzed using χ2 and κ statistics. Results:A total of 120 (67.4%) of the 178 who underwent resection or transplantation had an NCB. On preoperative NCB, the majority of HCC cases were classified as well-differentiated (n = 35; 37.6%) or moderately differentiated (n = 44; 47.3%), while 14 (15.1%) cases were categorized as poorly differentiated. In contrast, when tumor grading was based on the final surgical specimen, there was a significantly higher proportion of HCC cases graded as poorly differentiated (well-differentiated, n = 34; 36.6%; moderately differentiated, n = 33; 35.5%; poorly differentiated, n = 26; 27.9%) (P < 0.05). The overall percent agreement of NCB and surgical pathology to determine tumor grade was poor (κ = 0.18, P < 0.0001). Whereas final pathologic tumor grade predicted the presence of microscopic vascular invasion (well, 15.7%; moderate; 31.9%, poor; 58.4%; P = 0.001), NCB grade did not (well, 23.7%; moderate, 28.0%; poor, 25.4%; P = 0.65). Conclusions:Selection of candidates for transplantation based on NCB tumor grade may be misleading, as NCB tumor grade often did not correlate with grade or presence of microscopic vascular invasion on final pathology. Clinicomorphologic criteria (tumor size, number) should remain the major determinants of eligibility for transplantation.

Colorectal Liver Metastases Recurrence and Survival Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection-Radiofrequency Ablation

HYPOTHESIS Although radiofrequency ablation (RFA) is increasingly an accepted option for patients with colorectal liver metastases, patients treated with resection vs RFA may have different tumor biology profiles, which might confound the relationship between choice of liver-directed therapy and outcome. DESIGN Retrospective review of a prospectively collected database. SETTING Major hepatobiliary center. PATIENTS Between January 1, 1999, and August 30, 2006, 258 patients with colorectal liver metastases underwent hepatic resection with or without RFA. MAIN OUTCOME MEASURES Evaluation of outcome following resection alone, combined resection-RFA, and RFA alone using 3 statistical methods (paired-match control, Cox proportional hazards multivariate model, and propensity index) to identify and adjust for potential confounding variables. RESULTS The median number of hepatic lesions was 2, and the median size of the largest lesion was 3.0 cm. One hundred ninety-two patients (74.4%) underwent resection alone, 55 patients (21.3%) underwent resection-RFA, and 11 patients (4.3%) underwent RFA alone. Patients who underwent resection-RFA had significantly increased risk of extrahepatic failure at 1 year vs patients who underwent resection alone or RFA alone (P < .05). On matched control and multivariate analyses, patients who underwent RFA with or without resection had significantly worse disease-free and overall survival than patients who underwent resection alone. Propensity score methods revealed that the aggregate distribution of clinical risk factors for resection-RFA was markedly different from that for resection alone. This suggested a lack of comparability to allow for statistical comparisons in the assessment of causal inferences regarding the efficacy of RFA therapy. CONCLUSION Although results of matched control and multivariate analyses suggested that RFA with or without resection was associated with worse outcome, propensity score methods revealed that the resection-RFA and resection-alone groups were different with regard to baseline tumor and treatment-related factors, making causal inferences about the efficacy of RFA unreliable.

Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified

To date, no consensus has been reached regarding which primary tumor subtypes are managed appropriately with hepatic metastectomy. Specifically, the role of hepatic resection for metastatic periampullary or pancreatic adenocarcinoma remains controversial.

Patterns of Recurrence Following Liver Resection for Colorectal Metastases: Effect of Primary Rectal Tumor Site

HYPOTHESIS Patients with rectal adenocarcinoma are at increased risk of locoregional recurrence compared with patients with colon cancer. This may affect the pattern of recurrence and survival rates following hepatic resection of liver metastases from rectal adenocarcinoma. DESIGN Retrospective review of a prospectively collected cancer center database. PATIENT AND METHODS From April 1, 1984, to December 31, 2005, 582 patients with liver metastases from a primary colorectal adenocarcinoma underwent hepatic resection. Clinical and pathological factors were analyzed using Cox regression analyses and log-rank tests. RESULTS Of 582 patients, 141 (24.2%) had liver metastases from a primary rectal tumor site. Treatment of the primary rectal tumor most frequently included chemoradiation therapy (59.6%) and low anterior resection (63.1%). Most rectal tumors were pathological stage T3/T4 (85.8%) and N1 (68.1%). Treatment directed at the hepatic metastases included resection only (81.5%), resection plus radiofrequency ablation (17.8%), or radiofrequency ablation only (0.7%). With a median follow-up time of 30.7 months, 80 of 141 patients (56.7%) developed recurrence; 23 patients (16.3%) developed recurrence in the pelvis. Of 23 patients with pelvic recurrence, 56.5% also developed recurrence in the liver. The 3- and 5-year survival rates for all patients were 62.4% and 36.4%, respectively. Of 80 patients who had a recurrence following hepatic metastectomy, 23 (28.8%) underwent another operation. Following repeat metastectomy, 3- and 5-year survival rates were 76.7% and 38.6%, respectively. CONCLUSIONS Following resection of hepatic rectal metastases, pelvic recurrence is relatively common, and most patients with pelvic recurrence will also develop recurrence in the liver. Surgery for recurrent disease following hepatic resection of rectal metastases is warranted among well-selected patients.

Liver-Directed Surgery for Metastatic Squamous Cell Carcinoma to the Liver: Results of a Multi-Center Analysis

BackgroundThe role of hepatic resection for metastatic squamous cell carcinoma (SCC) remains unknown. The current study evaluates the role of hepatic resection in patients with metastatic SCC to the liver.MethodsBetween 1988 and 2006, 52 patients underwent hepatic resection of metastatic SCC at eight major cancer centers. Clinicopathologic factors were analyzed with regard to disease-free survival (DFS) and overall survival (OS).ResultsPrimary SCC site was anal (n = 27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7). Treatment of primary SCC was chemotherapy ± radiotherapy alone (n = 29), chemotherapy ± radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty-seven patients underwent resection alone, 2 resection + radiofrequency ablation (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) = 2.02) and positive surgical margin (HR = 2.33). The overall median survival after hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors associated with worse overall survival included synchronous disease (HR = 4.09), hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR = 1.83).ConclusionsThe majority of patients will recur following hepatic resection of SCC. Long-term survival, however, can be achieved following surgical resection of SCC liver metastasis, especially in patients who present with limited metachronous disease amenable to margin negative resection.

Rationale for complete metastasectomy in patients with stage IV metastatic melanoma

Patients with stage IV melanoma have usually been treated with systemic therapies; however, the overall survival for patients with this approach is disappointing. A complete surgical resection of metastatic disease to stage IV sites offers the best chance to maximize survival. This review article will present data supporting the position that if a complete metastasectomy is technically feasible, then surgery should be strongly considered the first option for properly selected patients with stage IV melanoma. J. Surg. Oncol. 2011; 104:420–424.

Nodal status, number of lymph nodes examined, and lymph node ratio: What defines prognosis after resection of colon adenocarcinoma?

BACKGROUND Lymph node ratio (LNR) has been proposed as an optimal staging variable for colorectal cancer. However, the interactive effect of total number of lymph nodes examined (TNLE) and the number of metastatic lymph nodes (NMLN) on survival has not been well characterized. STUDY DESIGN Patients operated on for colon cancer between 1998 and 2007 were identified from the Surveillance, Epidemiology, and End Results database (n = 154,208) and randomly divided into development (75%) and validation (25%) datasets. The association of the TNLE and NMLN on survival was assessed using the Cox proportional hazards model with terms for interaction and nonlinearity with restricted cubic spline functions. Findings were confirmed in the validation dataset. RESULTS Both TNLE and NMLN were nonlinearly associated with survival. Patients with no lymph node metastasis had a decrease in the risk of death for each lymph node examined up to approximately 25 lymph nodes, while the effect of TNLE was negligible after approximately 10 negative lymph nodes (NNLN) in those with lymph node metastasis. The hazard ratio varied considerably according to the TNLE for a given LNR when LNR ≥ 0.5, ranging from 2.88 to 7.16 in those with an LNR = 1. The independent effects of NMLN and NNLN on survival were summarized in a model-based score, the N score. When patients in the validation set were categorized according to the N stage, the LNR, and the N score, only the N score was unaffected by differences in the TNLE. CONCLUSIONS The effect of the TNLE on survival does not have a unique, strong threshold (ie, 12 lymph nodes). The combined effect of NMLN and TNLE is complex and is not appropriately represented by the LNR. The N score may be an alternative to the N stage for prognostication of patients with colon cancer because it accounts for differences in nodal samples.

A multi‐institution analysis of outcomes of liver‐directed surgery for metastatic renal cell cancer

OBJECTIVES Management of liver metastasis (LM) from a non-colorectal, non-neuroendocrine primary carcinoma remains controversial. Few data exist on the management of hepatic metastasis from primary renal cell carcinoma (RCC). This study sought to determine the safety and efficacy of surgery for RCC LM. METHODS A total of 43 patients who underwent surgery for RCC hepatic metastasis between 1994 and 2011 were identified in a multi-institution hepatobiliary database. Clinicopathologic, operative and outcome data were collected and analysed. RESULTS Mean patient age was 62.4 years and most patients (67.4%) were male. The mean tumour size of the primary RCC was 6.9 cm and most tumours (72.1%) were designated as clear cell carcinoma. Nine patients (20.9%) presented with synchronous LM. Among the patients with metachronous disease, the median time from diagnosis of the primary RCC to treatment of LM was 17.2 months (range: 2.1-189.3 months). The mean size of the RCC LM was 4.0 cm and most patients (55.8%) had a solitary metastasis. Most patients (86.0%) underwent a minor resection (up to three segments). Final pathology showed margin status to be negative (R0) in 95.3% of patients. Postoperative morbidity was 23.3% and there was one perioperative death. A total of 69.8% of patients received perioperative chemotherapy. Overall 3-year survival was 62.1%. Three-year recurrence-free survival was 27.3% and the median length of recurrence-free survival was 15.5 months. CONCLUSIONS Resection of RCC hepatic metastasis is safe and is associated with low morbidity and near-zero mortality. Although recurrence occurs in up to 50% of patients, resection can be associated with long-term survival in a well-selected subset of patients.