Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and combined resection-radiofrequency ablation. A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. Population-based audit of colorectal cancer management in two UK health regions. Colorectal Cancer Working Group, Royal College of Surgeons of England Clinical Epidemiology and Audit Unit. Nonoperative management of primary colorectal cancer in patients with stage IV disease. Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients. First-line chemotherapy vs bowel tumor resection plus chemotherapy for patients with unresectable synchronous colorectal hepatic metastases. Postoperative surveillance in patients with colorectal cancer who have undergone curative resection: a prospective, multicenter, randomized, controlled trial. Detection of cervical high-grade squamous intraepithelial lesions from cytologic samples using a novel immunocytochemical assay (ProEx C). Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal.
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.
                Retrospective review of a prospectively collected database.
                Major hepatobiliary center.
                Between January 1, 1999, and August 30, 2006, 258 patients with colorectal liver metastases underwent hepatic resection with or without RFA.
                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.
                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.
                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. A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.
                This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.
                Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.
                Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.
                This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased. To obtain information on the contemporary management of colorectal cancer in the UK to assist in the development of management guidelines, an independent, 1-year population audit was carried out in Trent Region and Wales.
                Data were collected on all patients admitted to hospital with a new diagnosis of colorectal cancer in a 1-year period.
                Of 3520 patients, 3221 (91.5 per cent) had surgery. Emergency/urgent operations were carried out as the first procedure in 552 (17.1 per cent). Resection of the primary disease was achieved in 2859 (81.2 per cent) and this was deemed curative in 2070 (58.8 per cent). Twenty-one per cent of all patients had metastatic disease at presentation. Overall, 30-day operative mortality was 7.6 per cent (21.7 per cent for emergency/urgent and 5.5 per cent for scheduled/elective procedures). Anastomotic dehiscence occurred in 105 patients (4.9 per cent); this was 3.9 per cent after colonic resections and 7.9 per cent after anterior rectal resections. Elective rectal excision resulted in a permanent stoma in 486 of 1054 patients (46 per cent).
                This initial report from a comprehensive, independent audit of colorectal cancer management shows improvement in some aspects of treatment as evidenced by improved anastomotic dehiscence and stoma rates when compared with previous studies. However, there has been little improvement in the proportion of patients presenting with advanced disease, and curative resection rates remain low. Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease.
                A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease.
                Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group).
                Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer. Surgical resection of primary colorectal cancer (CRC) in patients with stage IV disease at initial presentation remains controversial. Although bowel resection to manage symptoms such as bleeding, perforation, or obstruction has been advocated, management of asymptomatic patients has not been well defined. Patient-dependent factors (performance status, comorbid disease) and extent of distant metastases are among the considerations that impact on the decision to proceed with surgical management in asymptomatic stage IV CRC patients. We postulated that selected patients might benefit from elective resection of the asymptomatic primary CRC. The extent of distant metastases was objectively measured by several methods to identify potential prognostic variables that may help guide patient selection in this population.
                We reviewed hospital and colorectal service databases for the years 1996 to 1999. Stage IV patients who had colorectal resections with gross residual metastatic disease were identified (n = 209). Among these 209 patients, 82 patients operated on for symptoms (obstruction, perforation, bleeding, or pain) were excluded, leaving 127 patients who underwent elective resection of their asymptomatic primary CRC. Over the same time period, 103 stage IV patients who did not undergo resection were identified. Data on patient characteristics and clinical management were collected. A radiologist performed an independent review of available CT scans to assess extent of liver disease. The chi-square test was used for analysis of categoric data and Student's t-test for continuous variables. Survival was determined by the Kaplan-Meier method and distributions compared by the log rank test. Multivariate analysis was performed using Cox regression.
                The resected group could be easily distinguished from the nonresected group by a higher frequency of right colon cancers (p = 0.03) and metastatic disease restricted to the liver (p = 0.02) or one other site apart from the primary tumor (p = 0.02). Resected patients had prolonged median (16 versus 9 months, p < 0.001) and 2-year (25% versus 6%, p < 0.001) survival compared with patients never resected. Univariate analysis identified three significant prognostic variables (number of distant sites involved, metastases to liver only, and volume of hepatic replacement by tumor) in the resected group. Volume of hepatic replacement was also a significant predictor of survival in Cox multivariate regression analysis (p = 0.01). Subsequent to resection of asymptomatic primary CRC, 26 patients (20%) developed postoperative complications. Median hospital stay was 6 days. Two patients (1.6%) died within 30 days of surgery.
                Stage IV patients selected for elective palliative resection of asymptomatic primary colorectal cancers had substantial postoperative survival that was significantly better than those never having resection. Limited metastatic tumor burden and less extensive liver involvement were associated with better survival and a higher likelihood of benefit from elective bowel resection in asymptomatic patients with incurable stage IV CRC. Bowel resection followed by chemotherapy is a better management strategy than immediate chemotherapy in asymptomatic patients with colorectal cancer and unresectable liver-only metastases at presentation.
                Retrospective study.
                University hospital.
                Sixty-five consecutive symptom-free colorectal cancer patients with unresectable synchronous metastases confined to the liver undergoing bowel tumor resection plus systemic chemotherapy (42 patients [resection group]) or chemotherapy first (23 patients [chemotherapy group]).
                Long-term survival and identification of prognostic indicators of outcome.
                In the resection group, the mean and median overall survival times were shown to be significantly better than those in the chemotherapy group (P = .03). Performance status, basal serum levels of lactic dehydrogenase and alkaline phosphatase, percentage of liver involvement, potentially curative resection of the bowel tumor, and type of treatment (resection vs chemotherapy) were demonstrated to be the only variables significantly correlated with long-term survival. On multivariate analysis, performance status, extent of liver involvement, and type of treatment were shown to be the only covariates independently associated with survival rate. The rate of liver metastasis downstaging with subsequent curative hepatic resection was clearly associated with good performance status, limited liver involvement, and resection of the bowel tumor.
                Achieving complete cure in asymptomatic colorectal cancer patients with unresectable synchronous liver-only metastases appears to be mostly the result of shrinkage and resection of hepatic metastases. In patients with good performance status and limited liver involvement, bowel tumor resection appears to be the best treatment option for this purpose. Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability.
                Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added.
                A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm.
                A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least. Routine liquid-based cytology (LBC) provides excellent sensitivity for the detection of cervical high-grade squamous intraepithelial lesion (HSIL); however, its specificity is low. Consequently, many women who have atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology undergo unnecessary colposcopy. The authors hypothesized that a novel immunocytochemical assay (ProEx C) that can be performed on LBC slides had a significantly higher positive predictive value (PPV) for biopsy-proven HSIL compared with routine LBC.
                The ProEx C immunocytochemical assay utilizes a cocktail of monoclonal antibodies directed against proteins associated with aberrant S-phase cell cycle induction (topoisomerase IIA, minichromosome maintenance protein 2). The ProEx C reagents were validated in the authors' laboratory for staining and scoring reproducibility, open-vial stability, and accuracy before a retrospective analysis using these reagents was performed on 317 residual cytology samples. Sensitivity, specificity, PPV, and negative predictive value (NPV) for the detection of biopsy-proven HSIL were determined.
                The ProEx C assay was validated successfully in the authors' cytology laboratory. Using biopsy-proven HSIL as an endpoint, the ProEx C assay yielded a sensitivity of 85.3%, specificity of 71.7%, PPV of 44.6%, and NPV of 94.8%. Compared with the routine LBC results in the same cohort, the ProEx C sensitivity for biopsy-proven HSIL was 70.6% greater than HSIL+ cytology (50% vs. 85.3%). ProEx C also showed a 114% increase in PPV relative to ASC-US cytology (21.1% vs. 44.6%).
                The ProEx C immunocytochemical assay can be integrated into a clinical cytology laboratory and may increase the PPV of LBC for biopsy-proven HSIL. Transcatheter arterial chemoembolization (TACE) improves the treatment of hepatocellular carcinoma (HCC) by causing tumour necrosis and shrinkage. Fifty-two patients with resectable large HCC (defined as a maximal tumour diameter of 10 cm or more) were prospectively randomized into two groups: group 1 comprised 24 patients who had 1-5 sessions of TACE before operation; group 2 consisted of the other 28 patients, on whom surgery was performed without delay. Tumour volume was reduced to a mean (s.d.) of 42.8 (15.3) per cent in 16 patients in group 1, but remained unchanged in four and increased in size in a further four. Patients in group 1 had a slightly longer operating time (5.5 versus 4.6 h, P = 0.09), a higher rate of concomitant resection of adjacent organs (58 versus 25 per cent, P = 0.03) and a higher rate of histological invasion to these organs (33 versus 4 per cent, P = 0.01). No difference was found between the two groups in operative blood loss, operative morbidity and mortality rates, and pathological staging. The disease-free survival rate in the two groups was similar, but the incidence of extrahepatic cancer recurrence was higher in group 1 (57 versus 23 per cent, P = 0.03). The actuarial survival rate was also significantly worse in group 1 when determined from the time of detection of the tumour (P = 0.03) or from operation (P = 0.01). It is concluded that preoperative TACE for resectable large HCC should be avoided because it does not provide complete necrosis in large tumours and results in delayed surgery and difficulty in the treatment of recurrent lesions, without any benefit.
There is no high quality evidence on biopsy versus resection for HGG that can be used to guide management. The single included RCT is of inadequate methodology to reach reliable conclusions. Further large multi-centred RCTs are required to conclusively answer the question of whether biopsy or resection is the best initial surgical management for HGG.