S. Fenwick

Hepatic resection and transplantation for primary carcinoid tumors of the liver.

Objective:To discuss the diagnosis and management of primary carcinoid tumors of the liver in light of our experience and a literature review. Summary Background Data:Carcinoid tumors of the liver are rare and pose a diagnostic and management dilemma. This series is the largest reported and the only one to include liver transplantation as a treatment option. Methods:Between March 1994 and May 2002, we treated 8 patients (4 male, 4 female) with primary hepatic carcinoid tumors. Carcinoid syndrome complicated only 1 of the cases. Treatment was by liver resection in 6 patients and orthotopic liver transplantation in 2. Results:The diagnosis was confirmed histologically with light microscopy and immunohistochemistry in the absence of an alternative primary site. Six patients remain alive and disease free after follow-up of more than 3 years: 39, 43, 45, 50, 50, and 95 months. Two patients are recently postoperative. Conclusions:Active exclusion of an extrahepatic primary site is essential for the diagnosis of primary carcinoid of the liver. The mainstay of treatment should be liver resection, although liver transplantation may be considered in patients with widespread hepatic involvement. A radical surgical approach is warranted as this disease carries a better prognosis than for other primary hepatic tumors and for secondary hepatic carcinoids.

The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases

BACKGROUND & AIMS Cyclooxygenase-2 (COX-2) is a potential target for chemotherapy of colorectal cancer (CRC). We tested the antineoplastic activity of the selective COX-2 inhibitor rofecoxib on human CRC liver metastases by measuring surrogate markers of tumor growth and angiogenesis in a randomized, double-blind, placebo-controlled trial. METHODS Patients undergoing liver resection surgery for metastatic disease were randomized to receive rofecoxib 25 mg daily or placebo before surgery (duration, >14 days). The apoptosis index (AI; neocytokeratin 18), proliferation index (PI; Ki-67), and microvessel density (MVD; CD31) were measured in metastases by immunohistochemistry. The effect of rofecoxib on COX-2-positive HCA-7 human CRC cell PGE(2) synthesis, proliferation, and apoptosis in vitro was also investigated. RESULTS Patients who received rofecoxib (n = 23) and placebo (n = 21) were well matched regarding clinical and metastasis characteristics. The mean (range) duration of rofecoxib therapy was 26 (14-46) days. Rofecoxib-treated metastases had a 29% decrease in MVD (mean, 25.1 [SEM, 2.7] per hpf) compared with placebo-treated tissue (32.5 [SEM, 4.5] per hpf; P = 0.15). There was little difference in AI (rofecoxib mean, 2.03% [SEM, 0.43%] vs. placebo 1.39% [SEM, 0.39%]) or PI (rofecoxib 54.7% [SEM, 5.1%] vs. placebo 52.6% [SEM, 5.6%]). Rofecoxib-induced growth arrest and apoptosis of HCA-7 cells occurred only at concentrations (>10 micromol/L), which were significantly higher than the IC(50) for COX-2 inhibition. CONCLUSIONS Rofecoxib may negatively regulate angiogenesis in human CRC liver metastases. The absence of a significant, direct effect of rofecoxib on epithelial cells in liver metastases in vivo mirrors the lack of activity on human CRC cells at pharmacologically relevant concentrations in vitro.

Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases†

The evidence surrounding optimal follow‐up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time.

Randomized clinical trial of prehabilitation before planned liver resection

Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4‐week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis.

Microwave ablation with or without resection for colorectal liver metastases

BACKGROUND Ablation with or without resection for colorectal liver metastases has been suggested as a potential method of improving survival if complete surgical resection is not possible. This study assessed the safety and efficacy of surgical microwave ablation (MWA) with or without resection for colorectal liver metastases. METHODS A retrospective case series was reviewed. Data was extracted for all patients treated with open MWA with or without resection for colorectal liver metastases. Endpoints included postoperative 30-day morbidity and mortality, local treatment failure, disease free survival and overall survival. RESULTS A total of 43 patients with technically irresectable disease were treated with MWA; 28 underwent combined MWA and resection, whilst 15 underwent MWA as the sole treatment modality. Overall post-operative morbidity was 35%, 30-day postoperative mortality 2%. At a median follow-up of 15 months, local treatment failure was observed in 4% of ablated lesions. 3-year OS was 36% for MWA group, compared to 45% for the combined ablate/resect group with 3-year DFS of 32% and 8% respectively. CONCLUSION Microwave ablation with or without resection is a safe and effective method of achieving local disease control. Ablation with or without resection is associated with good long-term outcomes, and may be a suitable treatment option for small non-resectable colorectal liver metastases.

Cyclooxygenase-2 expression in colorectal cancer liver metastases

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n=25; score 2, n=29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan–Meier survival analysis and log rank test, both P=0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.

Combined Ablation and Resection (CARe) as an Effective Parenchymal Sparing Treatment for Extensive Colorectal Liver Metastases

Background Combined intra-operative ablation and resection (CARe) is proposed to treat extensive colorectal liver metastases (CLM). This multicenter study was conducted to evaluate overall survival (OS), local recurrence-free survival (LRFS), hepatic recurrence-free survival (HRFS) and progression-free survival (PFS), to identify factors associated with survival, and to report complications. Materials and Methods Four centers combined retropectively their clinical experiences regarding CLM treated by CARe. CLM characteristics, pre- and post-operative chemotherapy regimens, surgical procedures, complications and survivals were analyzed. Results Of the 288 patients who received CARe, 210 (73%) had synchronous and 255 (88%) had bilateral CLM. Twenty-two patients (8%) had extrahepatic disease. Median follow-up was 3.17 years (95%CI 2.83–4.08). Median OS was 3.33 years (95%CI 3.08–4.17) and 5-year OS was 37% (95%CI 29–45). One- and 5-year LRFS from ablated lesions were 87.9% (95%CI 83.3–91.2) and 78.0% (95%CI 71–83), respectively. Median HRFS and PFS were 14 months (95%CI 11–18) and 9 months (95%CI 8–11), respectively. One hundred patients experienced complications: 29 grade I, 68 grade II–III–IV, and three deaths. In the multivariate models adjusted for center, the occurrence of complications was confirmed as a major independent factor associated with 3-year OS (HR 1.80; P = 0.008). Five-year OS was 25.6% (95%CI 14.9–37.6) for patients with complications and 45% (95%CI 33.3–53.4) for patients without. Conclusions Recent strategies facing advanced CLM include non-anatomic resections, portal-induced hypertrophy of the future remnant liver and aggressive medical preoperative treatments. CARe has the qualities of an approach that allows effective tumor clearance while maintaining good tolerance for the patient.

Cholecystectomy-related bile duct and vasculobiliary injuries

Combined vasculobiliary injury is a serious complication of cholecystectomy. This study examined medium‐ to long‐term outcomes after such injury.

The Liverpool uveal melanoma liver metastases pathway: Outcome following liver resection

To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma.

Uveal Melanoma UK National Guidelines

The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.