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Objective: The aim of this study was to describe the surgeon's ability to accurately predict the margin following resection of colorectal liver metastases (CRLMs)., Background: The decision to resect CRLM is based on the surgeon's ability to predict tumor-free resection margins. However, to date, no study has evaluated the accuracy of surgeon margin prediction., Methods: In this single-institution prospective study, the operating attending and fellow independently completed a preoperative and postoperative questionnaire describing their expected resection margin in 100 consecutive cases (200 assessments) of CRLM resections. In cases with multiple metastases, the closest margin was assessed as the margin of interest for the primary outcome. Surgeon assessments were compared with the gold-standard histopathologic assessment., Results: After excluding aborted cases, 190 preoperative and 190 postoperative assessments from 95 cases were included in the analysis. The pathologic margin was noted to be wide (≥1 cm), 1 mm to 1 cm, narrow (<1 mm), and positive in 28 (29.5%), 55 (57.9%), 5 (5.3%), and 7 (7.4%) cases, respectively. The 88 cases with negative margins were all predicted to be negative. None of the cases with positive margins were predicted to be positive. Ninety-one (48%) preoperative and 104 (55%) postoperative predictions were accurate. The sensitivity of predicting a margin <1 mm was 8.3% preoperatively and 16.7% postoperatively. The positive predictive value for preoperative and postoperative predictions of margin <1 mm was 18.2% and 26.7%, respectively., Conclusions: Surgeons are inaccurate at predicting positive and close surgical margins following resection of CRLM. A predicted close margin should not necessarily preclude resection., Competing Interests: A.C.W. consults for Biosapien and Histosonics and received honorarium for teaching by Medtronic and AstraZeneca. J.A.D.’s spouse is employed by American Regent Pharmaceuticals. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate whether patient-controlled epidural analgesia (PCEA) improves postoperative pain during ambulation following elective open hepatectomy., Background: Strategies to alleviate postoperative pain are a critical element of recovery after surgery. However, the optimal postoperative pain management strategy following open hepatectomy remains unclear., Methods: We conducted a prospective, nonblinded, randomized comparison of PCEA (intervention) versus intravenous patient-controlled analgesia (IV PCA; control) for postoperative pain following elective open hepatectomy. The primary end point was pain during ambulation on postoperative day (POD) 2. The study was powered to detect a clinically significant 2-point difference on the pain numeric rating scale (NRS). Secondary end points included pain at rest, morbidity, time to return of bowel function, and length of stay., Results: From 2015 to 2020, 231 patients were randomized (116 patients in the PCEA arm and 115 in the IV PCA arm). The incidence of epidural failure was 3% (n=4/116), with no epidural-related complications. Patients in the PCEA arm had a <2-point difference in NRS pain scores during ambulation on POD 2 vs. IV PCA (median 4.0 vs. 5.0, P <0.001). There was no difference in overall complications between the PCEA and IV PCA arms (33% vs. 40%, P =0.276). Secondary outcomes, including pain scores at rest, were similar between the study arms., Conclusions: PCEA was safe following open hepatectomy and was associated with a small difference in pain with activity on POD 2 that did not reach our pre-specified definition of clinical significance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Controversy exists regarding the safety and feasibility of minimally invasive resection for lesions in segments 7 or 8. We compare outcomes of minimally invasive surgery (MIS) and Open parenchymal sparing liver resections at two high-volume centers., Methods: From 2003 to 2016 we identified patients who underwent MIS or Open resections for lesions in segments 7 or 8 at two institutions (MSKCC and SGH). Outcomes were compared using univariate and multivariate analyses., Results: Two-hundred and forty-five patients underwent resection of lesions in segments 7 or 8 (MIS 30% and Open 70%). Compared to the Open group, the MIS group had longer operative time (223 ± 88 vs 188 ± 72 minutes, P = .003), lower blood loss (297 ± 287 vs 448 ± 670 mL, P = .03), and shorter mean length of stay (5.2 ± 7.4 vs 8.3 ± 11.7 days, P < .001), which remained significant on multivariate analysis. No differences in Pringle time, rate of postoperative complications, or R0 resections were detected., Conclusions: With appropriately selected patients treated by experienced MIS hepatopancreatobiliary surgeons, MIS resection of segments 7 or 8 is safe with similar rates of complications and R0 resections, with significantly less blood loss and shorter length of stay., (© 2020 Wiley Periodicals LLC.)

Objective: To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM)., Background: Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection., Methods: Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders., Results: Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors., Conclusion: Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

Background: Obesity and metabolic syndrome are associated with inflammatory hepatic parenchymal disease (HPD) and increased risk for recurrence after resection of colorectal liver metastases (CRLM). The independent impact of HPD on recurrence patterns has not been well defined., Methods: The nonalcoholic fatty liver disease activity score (NAS) was used to quantify HPD including steatosis and fibrosis for all patients with completely resected CRLM between April 2003 and March 2007. Clinicopathologic factors, perioperative history, and outcomes were compared with the NAS. Fisher's exact test was used to examine the association between severe HPD (NAS ≥ 3) with clinical and perioperative characteristics. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS). The cumulative incidences of recurrence [any intrahepatic recurrence (IHR), extrahepatic recurrence only (EHR), and death without recurrence (DWR)] were estimated using competing risks methods., Results: Among the 357 patients included in this study, microsteatosis was noted in 124 (35%) patients, severe HPD in 31 (9%), steatohepatitis in 14 (4%), and sinusoidal injury in 36 (10%). After median follow-up of 127 months (range 4-175 months), 10-year RFS was 22% [95% confidence interval (CI) 17-27%]. Ten-year cumulative incidence for IHR, EHR, and DWR was 37%, 30%, and 12%, respectively. After controlling for confounders, NAS ≥ 3 was independently associated with higher risk of IHR [hazard ratio (HR) 1.76, 95% CI 1.07-2.90, p = 0.027] and lower risk of EHR (HR 0.18, 95% CI 0.04-0.75, p = 0.019) on multivariable analysis., Conclusions: Severe HPD was associated with increased IHR risk and decreased EHR risk. Future investigation into whether improving HPD from reversible etiologies can reduce the risk for IHR is warranted.

Objective: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM)., Background: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied., Methods: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed., Results: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200 μg/L, and clinical risk score (CRS) ≥4. Factors associated with worse RFS were node-positive primary tumor, ≥4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut., Conclusions: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA ≤ 200 μg/L and CRS < 4.

Background: Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia., Study Design: We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide., Results: We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively., Conclusions: This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to evaluate outcomes after resection of colorectal liver metastases (CRLM) and concurrent extrahepatic disease (EHD), and to define prognostic factors., Background: There is increasing evidence to support resection of liver metastases and concurrent EHD in selected patients. Long-term survival data are lacking, and prognostic factors are not well defined., Methods: Retrospective review of 219 patients was undertaken between January 1992 and December 2012, who underwent hepatectomy for CRLM and resection of synchronous EHD. Survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. A scoring system for prognostication was developed., Results: The median, 3, 5, and 10-year overall survival were 34.4 months, 49%, 28%, and 10%, respectively. Disease recurred in 185 patients (90.2%) at a median of 8 months. There were 8 actual 10-year survivors. The site of EHD affected survival, with portal, retroperitoneal nodes and multiple sites associated with the worst prognoses. The size of the largest CRLM, the number of CRLM, unfavorable site of EHD, and progression of CRLM on neoadjuvant therapy were associated with overall survival on univariate and multivariate analyses. Three variables, assigned 1 point each, were used to create an EHD risk score: largest CRLM greater than 3 cm, greater than 5 CRLM, and unfavorable site of EHD. The resulting score was prognostic of overall and recurrence-free survival., Conclusions: Long-term survival is possible after resection of liver metastases and concurrent EHD, but true cure is rare. A proposed scoring system may identify patients most likely to benefit from surgery.

Objective: To evaluate the efficacy of surgical treatment for patients with isolated breast cancer liver metastases (BCLM)., Background: Single-arm retrospective studies have shown promising results associated with surgery for isolated BCLM; however, this treatment remains controversial and its role is not well-defined., Methods: A review of 2150 patients with BCLM who underwent treatment in a single institution was conducted, and 167 (8%) patients with isolated BCLM were identified. A case-control study was conducted to compare outcomes in patients with isolated BCLM who underwent surgery and/or ablation to patients who underwent conventional medical therapy., Results: A total of 167 patients were included (surgery/ablation: 69; medical: 98), with a median follow-up for survivors of 73 months. Patients in the surgical cohort more frequently had estrogen receptor-positive tumors and received adjuvant chemotherapy and radiotherapy for their primary breast tumor. The hepatic tumor burden was less and the interval from breast cancer diagnosis to BCLM was significantly longer (53 vs 30 months) in the surgical cohort. Patients undergoing surgical treatment had a median recurrence-free interval of 28.5 months (95% confidence interval (CI): 19-38) with 10 patients (15%) recurrence free after 5 years. There was no significant difference in overall survival (OS) between the surgical and medical cohorts (median OS: 50 vs 45 months; 5-year OS: 38% vs 39%)., Conclusions: Hepatic resection and/or ablation was not associated with a survival advantage. However, significant recurrence-free intervals can be accomplished with surgical treatment. Surgical intervention might be considered in highly selected patients with the goal of providing time off of systemic chemotherapy.

Background: In recent years, increasingly sophisticated tools have allowed for more complex robotic surgery. Robotic hepatectomy, however, is still in its infancy. Our goals were to examine the adoption of robotic hepatectomy and to compare outcomes between open and robotic liver resections., Methods: The robotic hepatectomy experience of 64 patients was compared to a modern case-matched series of 64 open hepatectomy patients at the same center. Matching was according to benign/malignant diagnosis and number of segments resected. Patient data were obtained retrospectively. The main outcomes and measures were operative time, estimated blood loss, conversion rate (robotic to open), Pringle maneuver use, single non-anatomic wedge resection rate, resection margin size, complication rates (infectious, hepatic, pulmonary, cardiac), hospital stay length, ICU stay length, readmission rate, and 90-day mortality rate., Results: Sixty-four robotic hepatectomies were performed in 2010-2014. Forty-one percent were segmental and 34 % were wedge resections. There was a 6 % conversion rate, a 3 % 90-day mortality rate, and an 11 % morbidity rate. Compared to 64 matched patients who underwent open hepatectomy (2004-2012), there was a shorter median OR time (p = 0.02), lower median estimated blood loss (p < 0.001), and shorter median hospital stay (p < 0.001). Eleven of the robotic cases were isolated resections of tumors in segments 2, 7, and 8., Conclusions: Robotic hepatectomy is safe and effective. Increasing experience in more centers will allow definition of which hepatectomies can be performed robotically, and will enable optimization of outcomes and prospective examination of the economic cost of each approach.

Background: Improvements in liver surgery have led to decreased mortality rates. Symptomatic perihepatic collections (SPHCs) requiring percutaneous drainage remain a significant source of morbidity., Study Design: A single institution's prospectively maintained hepatic resection database was reviewed to identify patients who underwent hepatectomy between January 2004 and February 2012., Results: Data from 2173 hepatectomies performed in 2040 patients were reviewed. Overall, 200 (9%) patients developed an SPHC, the majority non-bilious (75.5%) and infected (54%). Major hepatic resections, larger than median blood loss (≥360 ml), use of surgical drains, and simultaneous performance of a colorectal procedure were associated with an SPHC on multivariate analysis. Non-bilious, non-infected (NBNI) collections were associated with lower white blood cell (WBC) counts, absence of a bilio-enteric anastomosis, use of hepatic arterial infusion pump (HAIP), and presence of metastatic disease, and resolved more frequently with a single interventional radiology (IR) procedure (85 vs. 46.5%, p < 0.001) more quickly (15 vs. 30 days, p = 0.001)., Conclusions: SPHCs developed in 9% of patients in a modern series of hepatic resections, and in one third were non-bilious and non-infected. In the era of modern interventional radiology, the need for re-operation for SPHC is exceedingly rare. A significant proportion of minimally symptomatic SPHC patients may not require drainage, and strategies to avoid unnecessary drainage are warranted.

Objective: To compare surgical outcomes between matched central hepatectomy (CH) and extended hepatectomy (EH) groups., Background: Surgical choices for centrally located liver tumours are limited. The traditional EH harbours substantial risks, whereas CH is an alternative parenchymal-sparing resection that may improve peri-operative morbidity., Methods: A review of 4661 liver resections at a single institution was performed. The cases (CH) were matched in a 1:1 ratio with EH controls., Results: The CH group was matched for demographic, tumour and laboratory factors with either right EH or combined (right/left) EH groups (n = 63 per group). Colorectal liver metastases were the most common diagnosis occurring in 70% of the patients. Higher intra-operative blood loss was observed in the right EH(P = 0.01) and combined EH groups (P < 0.01) compared with the CH group. There was a trend towards lower 90-day morbidity in the CH group (43%) compared with the right EH(59%, P = 0.1) and combined EH groups (56%, P = 0.2). The length of hospital stay was significantly longer in the control groups (P < 0.01 for both). The control groups had significantly higher post-operative bilirubin and International Normalized Ratio (INR) levels compared with the CH group. A post-operative bilirubin higher than 4 mg/dl was observed in 2% of the CH group compared with 39% of the right EH group (P < 0.01) and 52% of the combined EH group (P < 0.01). No differences in the rates of bile leak/biloma, post-hepatectomy liver failure or 90-day mortality were found., Conclusions: CH, as compared with EH, was safe and associated with a shorter hospital stay and less post-operative liver dysfunction. CH should be considered in patients with centrally located tumours amenable to such a resection., (© 2015 International Hepato-Pancreato-Biliary Association.)

Background: Hepatic resection is considered the standard of care for patients with resectable colorectal liver metastases (CRLM), but the benefits of using systemic chemotherapy for these patients have not been completely proven. Although systemic chemotherapy is likely to improve recurrence-free survival (RFS), no differences in overall survival (OS) have been demonstrated to date. This study aimed to compare surgery plus systemic chemotherapy, regardless timing of administration, with surgery alone, analyzing long-term outcomes for patients with CRLM who underwent liver resection with curative intent., Methods: Systematic review and meta-analysis of studies published from January 1991 to December 2013 were used to compare surgery alone and surgery plus chemotherapy for patients with CRLM who underwent liver resection with curative intent. All randomized clinical trials (RCTs) were included in the study. Selection of high-quality observational comparative studies (OCSs) was based on a validated tool, the Methodological Index for Nonrandomized Studies. Comparison of RFS and OS was performed using a fixed-effects model and the hazard ratio (HR)., Results: Concerning OS, 5 studies (3 RCTs and 2 OCSs) comprising 2,475 patients were analyzed, and chemotherapy (1,024 patients) relatively improved OS rates for 23 % of the patients versus surgery alone (HR, 0.77; 95 % confidence interval [CI] 0.67-0.88; p < 0.001). Four studies, totaling 1,592 patients, reported RFS (3 using RCTs and 1 using OCSs), showing that chemotherapy (702 patients) relatively improved RFS for 29 % of the patients (HR, 0.71; 95 % CI 0.61-0.83; p < 0.001)., Conclusion: This meta-analysis demonstrated that the use of chemotherapy for patients with CRLM who underwent resection with curative intent is a worthwhile strategy for improving both RFS and OS.

Purpose: Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up., Methods: Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36 months after last PST. Factors associated with PST, EST, and outcomes were analyzed., Results: Of 952 patients who underwent resection, 594 (62 %) experienced recurrence (median interval = 13 months). Initial recurrences involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29 %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594, most commonly with a single site of recurrence (n = 149). Young age (p = 0.01), negative initial resection margin (p = 0.003), initial tumor size <5 cm (p = 0.006), and recurrence pattern (p < 0.001) were independently associated with PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival was 61 and 43 months in those with recurrence. Median survival of patients undergoing PST was 87 months compared to 34 months for those who did not., Conclusions: Recurrence is common after CLM resection, but 27 % of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.

Background: Liver resection is used to treat primary and secondary malignancies. Historically, these procedures were associated with significant complications, which may affect cancer-specific outcomes. This study analyzed the changes in morbidity and mortality after hepatic resection over time., Study Design: Records of all patients undergoing liver resection for a malignant diagnosis from 1993 to 2012 at Memorial Sloan Kettering were analyzed. Patients were divided into early (1993 to 1999), middle (2000 to 2006), and recent (2007 to 2012) eras. Major hepatectomy was defined as resection of 3 or more segments. Univariate and multivariate analyses were made with t-tests or Mann-Whitney tests., Results: There were 3,875 patients who underwent 4,152 resections for malignancy. The most common diagnosis was metastatic colorectal cancer (n = 2,476, 64% of patients). Over the study period, 90-day mortality rate decreased from 5% to 1.6% (p < 0.001). Perioperative morbidity decreased from 53% to 20% (p < 0.001). The percentage of major hepatectomies decreased from 66% to 36% (p < 0.001). The rate of perioperative transfusion decreased from 51% to 21% (p < 0.001). The spectrum of perioperative morbidity changed markedly over time, with abdominal infections (43% of complications) overtaking cardiopulmonary complications (22% of complications). Peak postoperative bilirubin (odds ratio [OR] 1.1, p < 0.001), blood loss (OR 1.5, p = 0.001), major hepatectomy (OR 1.3, p = 0.031), and concurrent partial colectomy (OR 2.4, p < 0.001) were independent predictors of perioperative morbidity. The mortality associated with trisectionectomy (6%) and right hepatectomy (3%) remained unchanged over time., Conclusions: Morbidity and mortality rates after partial hepatectomy for cancer have decreased substantially as the major hepatectomy rate has dropped. Encouraging parenchymal preservation and preventing abdominal infections are vital for continued improvement of liver resection outcomes., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-induced hepatic injury is associated with increased splenic volume, thrombocytopenia, and decreased long-term survival. The current study investigates the relationship between change in splenic volume after preoperative chemotherapy and development of postoperative complications., Study Design: The study group consisted of 80 patients who underwent resection of CRCLM; half received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the other half did not (n = 40). The study group was compared with two control groups: a normal group composed of patients undergoing cholecystectomy for benign disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC) patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study group, the nontumoral liver was graded for steatosis and sinusoidal injury; operative and outcomes characteristics were also analyzed., Results: Before chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 ± 1.1 mL/kg, significantly higher than normal (2.5 ± 0.8 mL/kg; p < 0.001) and nonmetastatic CRC (2.6 ± 1.3 mL/kg; p < 0.05) patients, with higher splenic volume after 6 months of chemotherapy (4.2 ± 1.7 mL/kg; p < 0.01). After chemotherapy, splenic volume increase was associated with any perioperative complication (p < 0.01) and major complications (p < 0.05). Patients with ≥39% splenic volume increase (maximal chi-square test) were significantly more likely to have major complications (p < 0.01). Spleen volume changes were not correlated with change in platelet count (R(2) = 0.03; p = 0.301)., Conclusions: In patients with CRCLM, the presence of liver metastases and chemotherapy are associated with higher splenic volume. Percent splenic volume increase after 6 months of chemotherapy can aid preoperative risk stratification, as it was an independent predictor of major postoperative complications., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The reliable prediction of hepatocellular carcinoma (HCC) recurrence patterns potentially allows for the prioritization of patients for liver resection (LR) or transplantation., Objectives: The aim of this study was to analyse clinicopathological factors and preoperative Milan criteria (MC) status in predicting patterns of HCC recurrence., Methods: During 1992-2012, 320 patients undergoing LR for HCC were categorized preoperatively as being within or beyond the MC, as were recurrences., Results: After a median follow-up of 47 months, 183 patients developed recurrence, giving a 5-year cumulative incidence of recurrence of 62.5%. Patients with preoperative disease within the MC had better survival outcomes than those with preoperative disease beyond the MC (median survival: 102 months versus 45 months; P < 0.001). Overall, 31% of patients had preoperative disease within the MC and 69% had preoperative disease beyond the MC. Estimated rates of recurrence-free survival at 5 years were 61.8% for all patients and 53.8% for patients with initial beyond-MC status. Independent factors for recurrence beyond-MC status included preoperative disease beyond the MC, the presence of microsatellite or multiple tumours and lymphovascular invasion (all: P < 0.001). A clinical risk score was used to predict survival and the likelihood of recurrence beyond the MC; patients with scores of 0, 1, 2 and 3 had 5- year incidence of recurring beyond-MC of 9.0%, 29.5%, 48.8% and 75.4%, respectively (P < 0.0001)., Conclusions: Regardless of initial MC status, at 5 years the majority of patients remained disease-free or experienced recurrence within the MC after LR, and thus were potentially eligible for salvage transplantation (ST). Incorporating clinicopathological parameters into the MC allows for better risk stratification, which improves the selection of patients for ST and identifies patients in need of closer surveillance., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: After portal vein embolization (PVE), the future liver remnant (FLR) hypertrophies for several weeks. An early marker that predicts a low risk of post-hepatectomy liver failure can reduce the delay to surgery., Study Design: Liver volumes of 153 patients who underwent a major hepatectomy (>3 segments) after PVE for primary or secondary liver malignancy between September 1999 and November 2012 were retrospectively evaluated with computerized volumetry. Pre- and post-PVE FLR volume and functional liver volume were measured. Degree of hypertrophy (DH = post-FLR/post-functional liver volume - pre-FLR/pre-functional liver volume) and growth rate (GR = DH/weeks since PVE) were calculated. Postoperative complications and liver failure were correlated with DH, measured GR, and estimated GR derived from a formula based on body surface area., Results: Eligible patients underwent 93 right hepatectomies, 51 extended right hepatectomies, 4 left hepatectomies, and 5 extended left hepatectomies. Major complications occurred in 44 patients (28.7%) and liver failure in 6 patients (3.9%). Nonparametric regression showed that post-embolization FLR percent correlated poorly with liver failure. Receiver operating characteristic curves showed that DH and GR were good predictors of liver failure (area under the curve [AUC] = 0.80; p = 0.011 and AUC = 0.79; p = 0.015) and modest predictors of major complications (AUC = 0.66; p = 0.002 and AUC = 0.61; p = 0.032). No patient with GR >2.66% per week had liver failure develop. The predictive value of measured GR was superior to estimated GR for liver failure (AUC = 0.79 vs 0.58; p = 0.046)., Conclusions: Both DH and GR after PVE are strong predictors of post-hepatectomy liver failure. Growth rate might be a better guide for the optimum timing of liver resection than static volumetric measurements. Measured volumetrics correlated with outcomes better than estimated volumetrics., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative or remnant liver volume (RLV) after hepatic resection is a critical predictor of perioperative outcomes. This study investigates whether the accuracy of liver surgical planning software for predicting postoperative RLV and assessing early regeneration., Study Design: Patients eligible for hepatic resection were approached for participation in the study from June 2008 to 2010. All patients underwent cross-sectional imaging (CT or MRI) before and early after resection. Planned remnant liver volume (pRLV) (based on the planned resection on the preoperative scan) and postoperative actual remnant liver volume (aRLV) (determined from early postoperative scan) were measured using Scout Liver software (Pathfinder Therapeutics Inc.). Differences between pRLV and aRLV were analyzed, controlling for timing of postoperative imaging. Measured total liver volume (TLV) was compared with standard equations for calculating volume., Results: Sixty-six patients were enrolled in the study from June 2008 to June 2010 at 3 treatment centers. Correlation was found between pRLV and aRLV (r = 0.941; p < 0.001), which improved when timing of postoperative imaging was considered (r = 0.953; p < 0.001). Relative volume deviation from pRLV to aRLV stratified cases according to timing of postoperative imaging showed evidence of measurable regeneration beginning 5 days after surgery, with stabilization at 8 days (p < 0.01). For patients at the upper and lower extremes of liver volumes, TLV was poorly estimated using standard equations (up to 50% in some cases)., Conclusions: Preoperative virtual planning of future liver remnant accurately predicts postoperative volume after hepatic resection. Early postoperative liver regeneration is measureable on imaging beginning at 5 days after surgery. Measuring TLV directly from CT scans rather than calculating based on equations accounts for extremes in TLV., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Acute normovolemic hemodilution (ANH) decreases transfusion rates but adds to the complexity of anesthetic management during hepatectomy. A randomized controlled trial was conducted to determine if selecting patients for ANH using a transfusion nomogram improves management and resource use compared with selection using extent of resection., Study Design: One hundred fourteen patients undergoing partial hepatectomy were randomized to a clinical arm (ANH used for resection of ≥ 3 liver segments) or a nomogram arm (ANH used for predicted probability of transfusion ≥ 50% based on a previously validated nomogram). The primary end point was appropriate management, defined as avoidance of ANH in patients at low risk or use of ANH in patients at high risk for allogeneic red blood cell transfusions., Results: Between September 2009 and May 2011, 58 patients were randomized to the clinical arm and 56 to the nomogram arm. Demographics, diagnoses, extent of resection, blood loss, and incidence and grade of complications did not differ between the 2 groups. There were no differences in perioperative transfusions or laboratory values. Nomogram-based allocation did not change appropriate management overall (80% vs 76% in the clinical arm; p = 0.65), but did result in comparable perioperative outcomes and a trend toward decreased ANH use (30% vs 47%; p = 0.09), particularly in low blood loss (estimated blood loss ≤ 400 mL) cases (12% vs 25%; p = 0.04)., Conclusions: Although allocation of intraoperative management using a transfusion nomogram did not improve appropriate management overall, it more effectively identified low blood loss cases and reduced ANH use in patients least likely to benefit., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients undergoing liver resection for colorectal cancer liver metastasis (CRCLM) are often treated with chemotherapy before surgery. However, the associations between chemotherapy, liver injury, perioperative outcomes, and other confounding factors remain unclear. This study investigates the effect of preoperative chemotherapy for CRCLM on nontumoral liver histology and perioperative outcomes in a contemporary cohort., Study Design: Five hundred six patients underwent hepatic resection for CRCLM between April 2003 and March 2007. Histologic evaluation of nontumoral liver parenchyma for sinusoidal dilatation, steatosis, and steatohepatitis was performed in 384 cases for which tissue was available. Patient factors, tumor characteristics, chemotherapy regimens, histology of nontumoral liver, and perioperative morbidity were analyzed., Results: Two hundred fifty patients (65%) received preoperative chemotherapy for a median duration of 24 weeks. Irinotecan, increased body mass index (BMI), and diabetes mellitus (DM) were associated with hepatic steatosis and steatohepatitis. Sinusoidal dilatation was not associated with chemotherapy or any clinicopathologic factors. Perioperative blood transfusion was independently associated with an increased risk of any complication. Major postoperative complications were independently associated with major (≥ 3 segments) resections (57%) and perioperative blood transfusion. The use of any preoperative chemotherapy decreased the odds of major complications. Liver-related complications were independently associated with major resection and blood transfusion, but not with chemotherapy. Three postoperative deaths (0.8%) occurred, all in patients who were not treated with chemotherapy and had no evidence of liver injury., Conclusions: With appropriate patient selection, liver resection for CRCLM can be safely performed in patients treated with preoperative chemotherapy., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known., Methods: Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection., Results: One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis., Conclusion: In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The potential benefit of adjuvant hepatic arterial infusional floxuridine (HAI-FUDR) in addition to modern systemic chemotherapy using oxaliplatin or irinotecan remains unknown for patients with resected liver-confined colorectal metastases (CRLM). The principle aim of this study was to compare outcomes in patients receiving modern systemic chemotherapy with or without HAI-FUDR., Methods: Between 2000 and 2005, 125 patients underwent resection of CRLM followed by adjuvant HAI-FUDR plus dexamethasone (Dex) and concurrent systemic chemotherapy including oxaliplatin or irinotecan. These patients were compared retrospectively to 125 consecutive patients who received modern systemic chemotherapy alone after liver resection., Results: The median follow-up for all patients was 43 months. There were no differences in clinical risk score, disease-free interval, size of largest CRLM, number of CRLM, or prehepatectomy CEA level between the 2 groups. Adjuvant HAI-FUDR was associated with an improved overall and liver recurrence-free survival (liver RFS) and disease-specific survival (DSS). For the adjuvant HAI-FUDR group, the 5-year liver RFS, overall RFS, and DSS were 75%, 48%, and 79%, respectively, compared to 55%, 25%, and 55% for the systemic alone group (P < 0.01). On multivariate analysis, adjuvant treatment including HAI-FUDR was independently associated with improved liver RFS (HR = 0.34), overall RFS (HR = 0.65), and DSS (HR = 0.39), P < 0.01., Conclusions: Adjuvant HAI-FUDR combined with modern systemic chemotherapy is independently associated with improved survival compared to adjuvant systemic chemotherapy alone. A randomized clinical trial between these 2 regimens is justified.

Objective: To assess the effect of increasing body mass index, intra-abdominal fat, and outer abdominal fat on outcome in patients undergoing major hepatectomy., Design: Cohort study., Setting: Memorial Sloan-Kettering Cancer Center., Participants: We studied patients aged 19 to 86 years undergoing major hepatic resection between June 18, 1996, and November 6, 2001. Complications were extracted from a prospective database at a tertiary cancer center., Intervention: A total of 349 patients were grouped according to body mass index for analysis. Preoperative abdominal computed tomographic scans were examined and measurements of perinephric fat (as a surrogate for intra-abdominal fat) and outer abdominal fat taken at uniform anatomical locations., Main Outcome Measures: We compared 30-day mortality and morbidity figures, length of stay, and operating times., Results: Body mass index had an influence on operative time (P = .02) but no significant effect on mortality, frequency of any complications, frequency of severe complications, or length of stay (P = .80, P = .89, P = .16, and P = .81, respectively). Outer abdominal fat had no significant effect on any of the 5 outcome measures. Perinephric fat measurements had a significant effect on most outcome measures (P = .004 for mortality, P = .003 for frequence of complications, P < .001 for frequence of severe complications, and P = .001 for length of stay)., Conclusions: Outer appearances of obesity do not correlate with poor outcomes for major upper abdominal operations. A simple measurement of perinephric fat, as a surrogate for intra-abdominal fat, on preoperative imaging gives a more useful risk assessment for patients undergoing major upper abdominal operations.

Background: This study analyzes factors associated with differences in long-term outcomes after hepatic resection for metastatic colorectal cancer over time., Study Design: Sixteen-hundred consecutive patients undergoing hepatic resection for metastatic colorectal cancer between 1985 and 2004 were analyzed retrospectively. Patients were grouped into 2 eras according to changes in availability of systemic chemotherapy: era I, 1985 to 1998; era II, 1999 to 2004., Results: There were 1,037 patients in era I and 563 in era II. Operative mortality decreased from 2.5% in era I to 1% in era II (p = 0.04). There were no differences in age, Clinical Risk Score, or number of hepatic metastases between the 2 groups; however, more recently treated patients (era II) had more lymph node-positive primary tumors, shorter disease-free intervals, more extrahepatic disease, and smaller tumors. Median follow-up was 36 months for all patients and 63 months for survivors. Median and 5-year disease-specific survival (DSS) were better in era II (64 months and 51% versus 43 months and 37%, respectively; p < 0.001); but median and 5-year recurrence-free survival (RFS) for all patients were not different (23 months and 33% era II versus 22 months and 27% era I; p = 0.16). There was no difference in RFS or DSS for high-risk (Clinical Risk Score >2, n = 506) patients in either era. There was a marked improvement in both RFS and DSS for low risk (Clinical Risk Score < or =2, n = 1,094) patients., Conclusions: Despite worse clinical and pathologic characteristics, survival but not recurrence rates after hepatic resection for colorectal metastases have improved over time and might be attributable to improvements in patient selection, operative management, and chemotherapy. The improvement in survival over time is largely accounted for by low-risk patients., (Copyright 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To develop 2 instruments that predict the probability of perioperative red blood cell transfusion in patients undergoing elective liver resection for primary and secondary tumors., Summary Background Data: Hepatic resection is the most effective treatment for several benign and malign conditions, but may be accompanied by substantial blood loss and the need for perioperative transfusions. While blood conservation strategies such as autologous blood donation, acute normovolemic hemodilution, or cell saver systems are available, they are economically efficient only if directed toward patients with a high risk of transfusion., Methods: Using preoperative data from 1204 consecutive patients who underwent liver resection between 1995 and 2000 at Memorial Sloan- Kettering Cancer Center, we modeled the probability of perioperative red blood cell transfusion. We used the resulting model, validated on an independent dataset (n = 555 patients), to develop 2 prediction instruments, a nomogram and a transfusion score, which can be easily implemented into clinical practice., Results: The planned number of liver segments resected, concomitant extrahepatic organ resection, a diagnosis of primary liver malignancy, as well as preoperative hemoglobin and platelets levels predicted the probability of perioperative red blood cell transfusion. The predictions of the model appeared accurate and with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.71., Conclusions: Preoperative factors can be combined into risk profiles to predict the likelihood of transfusion during or after elective liver resection. These predictions, easy to calculate in the frame of a nomogram or of a transfusion score, can be used to identify patients who are at high risk for red cell transfusions and therefore most likely to benefit from blood conservation techniques.

Background: Surgical resection for patients with hepatic and extrahepatic (EHD) colorectal metastases is controversial. We analyzed our experience with hepatic resection in patients with concomitant EHD. The aims were to characterize survival, recurrence rates, and factors associated with outcome., Methods: From 1992 to 2007, 1,369 patients underwent resection of hepatic colorectal metastases, of whom 127 (9%) had concurrent resection of EHD. Survival and recurrence were compared between patients with and without EHD. Survival data were stratified by site of metastatic involvement. Variables potentially associated with survival were analyzed in univariate and multivariate analyses., Results: Median follow-up was 24 months (range 3-152 months). The 3- and 5-year survival for patients with concomitant EHD were 47% and 26%, respectively, compared with 67% and 49%, for those without EHD (P < 0.001). Among the patients with EHD, multivariate analysis identified higher clinical risk score, incomplete resection of all EHD, EHD detected intraoperatively, and having received neoadjuvant chemotherapy to be independently associated with a worse survival. Patients with portal lymph node metastases had worse survival than those with lung or ovarian metastases. Among patients who had a complete resection of all disease, 95% recurred., Conclusion: Concurrent resection of hepatic and EHD in well-selected patients is associated with a possibility of long-term survival. The presence of limited and resectable EHD should not be an absolute contraindication to resection. The site of EHD and the nearly universal recurrence rate must be taken into consideration.

Purpose: To develop a tool for predicting survival after liver resection for patients with stage IV colorectal cancer. By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure., Patients and Methods: All patients admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between January 1986 and December 1999 were included. A nomogram was developed as a graphical representation of a Cox proportional hazards regression model. The nomogram was verified for discrimination and calibration, both employing bootstrapping to obtain relatively unbiased estimates., Results: Using nodal status of the primary tumor, disease-free interval, size of the largest metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater than chance. The nomogram also had very good calibration., Conclusion: This nomogram is a predictive tool, upon external validation, that can routinely be used to counsel patients in making treatment decisions. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.

Objective: The aim of this study was to determine the results of liver resection for patients with bilateral hepatic metastases from colorectal cancer. We aimed to assess the evolution of the technical approach over time and correlations with morbidity, mortality, and oncologic outcome., Summary Background Data: Although hepatic resection for isolated colorectal metastases to the liver is thought to be beneficial when feasible, resection of bilateral liver metastases carries unique technical issues and is often associated with more aggressive tumor biology. Little has been written specifically about the results achieved in this subset of patients., Methods: Data from a prospectively maintained database of patients undergoing hepatic resection at a single institution over an 11-year time period were reviewed., Results: Resection of bilateral liver metastases from colorectal cancer was accomplished in 443 cases (440 patients) with a 29% incidence of major complications and a 5.4% 90-day mortality. Kaplan-Meier estimated 5-year disease-specific survival was 30% and 5-year recurrence-free survival was 18%. Operative technique changed over time toward a parenchymal-sparing approach as evidenced by the greater use of multiple simultaneous liver resections, wedge resections, and ablations. Similarly, there was a decrease in the use of major hepatectomies. This correlated with decreased mortality without change in disease-specific survival or liver recurrence., Conclusions: Resection of bilateral colorectal liver metastases can be accomplished with acceptable morbidity, mortality, and oncologic results. Increased use of a parenchymal-sparing approach is associated with decreased mortality without compromise in cancer-related outcome.