An evaluation study of trace element content in colorectal liver metastases and surrounding normal livers by X-ray fluorescence

Background Trace elements are involved in many key pathways involving cell cycle control. The levels of trace metals such as iron, copper, and zinc in colorectal liver metastases have not previously been assessed. Methods The trace element content in snap-frozen cancerous liver tissue from patients who underwent liver resection for colorectal liver metastases was compared with the normal surrounding liver (distant from the cancer) using X-ray fluorescence (XRF). Results X-ray fluorescence was performed on a total of 60 samples from 30 patients. Of these 29 matched pairs (of cancer and normal liver distant from cancer from the same patient) were eligible for univariate analysis. Iron (0.00598 vs. 0.02306), copper (0.00541 vs. 0.00786) and zinc (0.01790 vs. 0.04873) were statistically significantly lower in the cancer tissue than the normal liver. Iron, copper, and zinc were lower in the cancer tissue than in the normal liver in 24/29 (82.8%), 23/29 (79.3%), and 28/29 (96.6%) of cases respectively. Multivariate analysis of the 60 samples revealed that zinc was the only trace element decreased in the cancer tissue after adjusting for the other elements. Zinc levels were not affected by any of the histopathological variables. Conclusion Iron, copper, and zinc are lower in colorectal liver metastases than normal liver. An investigation into the pathways underlying these differences may provide a new understanding of cancer development and possible novel therapeutic targets.     

Classifying the Stage IV Colorectal Cancer: Prognostic Impact of Radical Resection for Colorectal liver Metastases and Proposal for a New Staging System

Currently, there is no universally accepted system to classify the stage IV colorectal cancer. Here, we analyze the prognostic impact of radical resection for colorectal liver metastases and propose a new staging system for stage IV colorectal cancer. A retrospective review was undertaken of 126 consecutive patients who underwent surgical treatment for colorectal liver metastases from January 1997 to January 2004. Based on the overall survival rates (Kaplan–Meier method) and surgical outcomes, we propose a new staging system for stage IV colorectal cancer. Patients were divided into two groups: patients who underwent initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22), and patients who underwent palliative resection for unresectable liver metastases (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years were 68.2 % (15/22), 40.9 % (9/22), and 18.2 % (4/22), respectively. The overall survival rates in group 2 at 1, 3, and 5 years were 54.8 % (57/104), 16.3 % (17/104), and 0 % (0/104), respectively. There was a significant difference in overall survival rates between both groups (p < 0.05). Based on the study results, we propose a new staging system where all distant metastases are grouped within stage IV and subclassified into resectable (R0 resection) and unresectable stages. Curative surgical treatment is a critical prognostic factor in colorectal liver metastases. The proposed new staging system for stage IV colorectal cancer is simple and is clinically useful to estimate the prognosis.     

Timing of Hepatectomy for Resectable Synchronous Colorectal Liver Metastases: For Whom Simultaneous Resection Is More Suitable - A Meta-Analysis

Background

The optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.

Methods

A systemic search for major databases and relevant journals from January 2000 to April 2013 was performed. The primary outcomes were postoperative mortality, morbidity, overall survival and disease-free survival. Other outcomes such as number of patients need blood transfusion and length of hospital stay were also assessed. Baseline analyses were conducted to find and correct potential confounding factors.

Results

22 studies with a total of 4494 patients were finally included. After correction of baseline imbalance, simultaneous and staged resections were similar in postoperative mortality (RR = 1.14, P = 0.52), morbidity (RR = 1.02, P = 0.85), overall survival (HR = 0.96, P = 0.50) and disease-free survival (HR = 0.97, P = 0.87). Only in pulmonary complications, simultaneous resection took a significant advantage (RR = 0.23, P = 0.003). The number of liver metastases was the major factor interfering with selecting surgical strategies. With >3 metastases, simultaneous and staged strategies were almost the same in morbidity (49.4% vs. 50.9%). With ≤3 metastases, staged resection caused lower morbidity (13.8% vs. 17.2%), not statistically significant.

Conclusions

The number of liver metastases was the major confounding factor for postoperative morbidity, especially in staged resections. Without baseline imbalances, simultaneous took no statistical significant advantage in safety and efficacy. Considering the inherent limitations of this meta-analysis, the results should be interpret and applied prudently.     

MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma

Objective

Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.

Methods

We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.

Results

All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01).

Conclusion

In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.     

Repeat hepatectomy justified in patients with early recurrence of colorectal cancer liver metastases: A systematic review and meta-analysis

BackgroundThe benefit of repeat hepatectomy in patients with early recurrence of colorectal cancer liver metastases (CRLM) is questioned, in particular in those suffering from recurrence within three to six months following initial hepatectomy. The aim of this review was therefore to assess whether disease-free interval was associated with overall survival in patients undergoing repeat hepatectomy for recurrent CRLM.MethodsA systematic review and meta-analysis was conducted, according to PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched from database inception to 6th June 2020. Observational studies describing results of repeat hepatectomy for recurrent CRLM, including (disease-free) interval between hepatic resections and overall survival were included. Patients undergoing repeat hepatectomy within three months or additional resection of extrahepatic disease were excluded from meta-analysis.ResultsThe initial search identified 2159 records, of which 28 were included for qualitative synthesis. A meta-analysis of 15 cohort studies was performed, comprising 1039 eligible patients. Median overall survival of 54.0 months [95 %-CI: 38.6–69.4] was observed after repeat hepatectomy in patients suffering from recurrent CRLM between three to six months compared to 53.0 months [95 %-CI: 44.3–61.6] for patients with recurrent CRLM between seven to twelve months (adjusted HR = 0.89, 95 %-CI: 0.66–1.18; p = 0.410), and 60.0 months [95 %-CI: 52.7–67.3] for patients with recurrent CRLM after twelve months (adjusted HR = 0.70, 95 %-CI: 0.53−0.92; p = 0.012).ConclusionsDisease-free interval is considered a prognostic factor for overall survival, but should not be used as selection criterion per se for repeat hepatectomy in patients suffering from recurrent CRLM.     

Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial

Purpose  Metastatic disease is a major cause of mortality in colorectal cancer patients. Even after complete resection of isolated liver metastases, recurrence develops in the majority of patients. Therefore, development of strategies to prevent recurrent liver metastases is of major clinical importance. The present prospectively randomised phase III trial investigates the efficiency of active specific immunotherapy (ASI) after liver resection for hepatic metastases of colorectal cancer. Methods  Patients with histologically confirmed liver metastases from colorectal cancer were randomised to the vaccination or control group. After complete resection of liver metastases, patients randomised to the vaccination group received six doses of Newcastle disease virus (NDV) infected autologous tumour cell vaccine (ATV-NDV). The primary end-point was overall survival, secondary end-points were disease-free survival and metastases-free survival. Results  Fifty-one patients were enrolled in the study with 50 patients available for analysis. The follow-up period was 116.1 ± 23.8 month in the vaccination arm and 112.4 ± 18.5 month in the control group. In the total patient group, no differences in the primary and secondary end-points were detected. Most interestingly, subgroup analysis revealed a significant advantage for vaccinated colon cancer patients with respect to overall survival [hazard ratio: 3.3; 95%, confidence interval (CI): 1.0–10.4; P = 0.042] and metastases-free survival (hazard ratio: 2.7; 95%, CI: 1.0–7.4; P = 0.047) in the intention-to-treat analysis. Conclusion  Active specific immunotherapy in unselected colorectal cancer patients was not effective for prevention of recurrent metastatic disease. However, in colon cancer patients, ASI with ATV-NDV appears to be beneficial prolonging overall and metastases-free survival.     

Elevated serum endothelin-1 levels in patients with colorectal cancer; relevance for prognosis

BACKGROUND: It has been demonstrated that the Doppler Perfusion Index (DPI) is increased in patients who are at risk of developing liver metastases from colorectal cancer. It has been postulated that a circulating hormonal factor is involved in the relative vasoconstriction throughout the splanchnic bed. Endothelin-1 (ET-1), a potent vasoconstrictor which has been associated with tumor growth and is produced by colorectal tumors, may play an important role in this phenomenon. In this paper the prognostic value of serum ET-1 in colorectal cancer is discussed. METHODS: Preoperative serum levels of ET-1 were assessed in three groups of patients: group A underwent resection of the colorectal tumor and remained free of recurrence (n=20); group B developed metachronous liver metastases at least six months after colorectal resection (n=14); and group C presented with colorectal cancer and synchronous liver metastases (n=22). RESULTS: The mean (SD) serum ET-1 levels in groups A, B and C were 1.59 (0.41) pmol/L, 1.70 (0.32) pmol/L and 1.85 (0.47) pmol/L, respectively. These values were significantly different from those of healthy controls (1.22 (0.31), p<0.05). Kaplan-Meier analyses revealed no prognostic value of preoperative serum ET-1 levels. CONCLUSIONS: These preliminary results demonstrate that serum ET-1 levels are raised in patients with colorectal cancer. Serum ET-1 levels do not seem to be of prognostic value for survival.     

KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis

Background

KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.

Methodology/Principal Findings

KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).

Conclusions/Significance

Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.     

Deficiency in Thrombopoietin Induction after Liver Surgery Is Associated with Postoperative Liver Dysfunction

Background and Aims

Thrombopoietin (TPO) has been implicated in the process of liver regeneration and was found to correlate with hepatic function in patients with liver disease. With this investigation we aimed to determine if perioperative TPO levels were associated with postoperative outcome in patients undergoing liver resection.

Methods

Perioperative TPO was analyzed prior to liver resection as well as on the first and fifth postoperative day in 46 colorectal cancer patients with liver metastasis (mCRC) as well as 23 hepatocellular carcinoma patients (HCC). Serum markers of liver function within the first postoperative week were used to define liver dysfunction.

Results

While circulating TPO levels significantly increased one day after liver resection in patients without liver cirrhosis (mCRC) (P < 0.001), patients with underlying liver disease (HCC) failed to significantly induce TPO postoperatively. Accordingly, HCC patients had significantly lower TPO levels on POD1 and 5. Similarly, patients with major resections failed to increase circulating TPO levels. Perioperative dynamics of TPO were found to specifically predict liver dysfunction (AUC: 0.893, P < 0.001) after hepatectomy and remained an independent predictor upon multivariate analysis.

Conclusions

We here demonstrate that perioperative TPO dynamics are associated with postoperative LD. Postoperative TPO levels were found to be lowest in high-risk patients (HCC patients undergoing major resection) but showed an independent predictive value. Thus, a dampened TPO increase after liver resection reflects a poor capacity for hepatic recovery and may help to identify patients who require close monitoring or intervention for potential complications.     

Effect of major liver resection on hepatic ureagenesis in humans

Changes in hepatic ureagenesis following major hepatectomy are not well characterized. We studied the relation between urea synthesis and liver mass before and after major hepatectomy in humans. Fifteen patients scheduled for resection of malignancies in otherwise healthy livers were studied. Pre- and postoperative liver volume was assessed by computerized tomography-volumetry. During surgery, a primed, continuous infusion of [(13)C]urea was administered intravenously, and arterial blood samples were obtained hourly. Indocyanine green clearance was determined before and after resection. Seven patients underwent major hepatectomy, and eight patients underwent minor [<5% functional liver volume (total volume -- tumor volume)] or no resection, serving as controls. Resected functional liver volume in the major hepatectomy group averaged 60%. Urea synthesis per gram of functional liver tissue increased 2.6-fold following major hepatectomy, maintaining whole body urea synthesis. Arterial ammonia remained unchanged throughout the study, whereas following hepatectomy a hyperaminoacidemia occurred. In conclusion, immediately following major hepatectomy, urea synthesis per gram of functional liver tissue increases rapidly and proportionately to the amount of liver tissue resected, maintaining whole body urea synthesis at preoperative levels. This rapid and complete adaptation suggests that the capacity of urea synthesis is not limiting the maximum resectable volume in otherwise healthy livers.     

Resection for colorectal cancer in the very old: are the risks too high?

Altogether 277 consecutive patients aged 70 or more who were admitted for resection of colorectal cancer between 1975 and 1985 were studied. The postoperative complications and mortality in the 175 patients aged 70-79 were compared with those in the 102 patients aged 80 or more. The overall mortality was 11%. Mortality was significantly higher after resection in the older age group even when deaths from widespread malignancy were excluded from the analysis. After curative resection mortality was 2% (2/120) in the younger group and 7% (4/60) in the older group, but after palliative resection of tumours with local or distant spread mortality was significantly higher, at 21% (9/44) and 38% (12/32), respectively. An equal but high proportion of patients in both age groups suffered major complications, but complications caused significantly more deaths in the older group. The length of stay in hospital was not significantly different between the age groups.Patients should not be denied resection of a colorectal cancer because of age alone, especially if a curative operation is possible. The increased risk of death from major complications, particularly after palliative resection, should, however, be taken into account when an operation on patients over 80 is being considered.     

Adjuvant liver perfusion in colorectal cancer: initial results of a clinical trial.

Fifty consecutive patients with colorectal cancer but no evidence of secondary deposits in the liver were included in an ongoing controlled clinical trial of adjuvant liver perfusion aimed at reducing the incidence of hepatic metastases. All patients had their primary tumour resected in the standard way. Twenty-six of the patients served as controls, and 24 received fluorouracil, 1 g daily, as a continuous infusion into the portal venous system during the first seven days after operation. The patients were matched for age, sex, and site and stage of the disease. The immediate postoperative mortality and morbidity did not differ significantly between the two groups. During the follow-up period (mean duration 15.5 months), however, six deaths occurred in the control group and only one in the perfusion group. At necropsy four of the controls had multiple liver metastases. Two of the surviving controls developed evidence of liver metastases, and two had a local recurrence. No patient in the perfusion group developed evidence of hepatic metastases. These initial results suggest that adjuvant portal venous perfusion with fluorouracil may reduce the incidence of liver metastases in colorectal cancer.     

Can Microwave Ablation be an Alternative to Resection for the Treatment of Neuroendocrine Liver Metastases?

Objective: Surgical resection of neuroendocrine tumor liver metastases has been proven to improve survival, but the benefit of microwave ablation as an alternative or adjunct to surgery has yet to be assessed. Our hypothesis is that ablation is equal to surgery in terms of local recurrence and survival.Methods: We conducted a retrospective analysis including all patients treated with microwave ablation and/or surgical resection for neuroendocrine liver metastases in our institution between 2008 and 2017.Results: A total of 47 patients and 68 treatments were analyzed, including 34 liver resections, 20 ablations, and 14 combined procedures. A total of 130 individual metastases were treated with ablation, representing a median of 4 per session (range 1–30). While no major complications occurred after ablation, we observed 11 minor and 3 major complications after open surgical resection (P = .0135). Length of stay was significantly shorter after ablation (P = .0008). The majority of patients (33/47, 70.2%) underwent curative procedures, 14 patients underwent (29.8%) debulking procedures. There was no difference in local recurrence rate between tumors treated with ablation or resection. Liver-only disease progression was detected in 29% of the patients and overall progression was detected in 66% of the patients. The mean survival was not significantly different between patients treated with ablation only versus resection with or without ablation (P = .1570). Overall survival was mean 75.3 months (6 to 374 months).Conclusion: Depending on the extent of the liver metastases, microwave ablation might be a safe alternative or addition to resection for neuroendocrine tumor liver metastases with low morbidity and high local efficiency.Abbreviations: CT = computed tomography; MWA = microwave ablation; NET = neuroendocrine tumor; PET = positron emission tomography; RFA = radiofrequency ablation; RFS = recurrence-free survival; SMWA = stereotactic microwave ablation     

Incidence and detection of occult hepatic metastases in colorectal carcinoma.

Isotope liver scan, ultrasonography, and computed tomography of the liver were performed during the postoperative period in 43 consecutive patients undergoing laparotomy for colorectal carcinoma. Obvious hepatic metastases were detected in six patients at the time of surgery. Eleven patients considered to have a disease-free liver at laparotomy developed hepatic metastases during the two-year follow-up period. These patients were considered to have had occult hepatic metastases at the time of surgery. Postoperative isotope liver scan, ultrasonography, and computed tomography detected the presence of overt metastases in four, five, and six patients respectively. Of the 11 patients with occult metastases, isotope liver scan, ultrasonography, and computed tomography detected one, three, and nine respectively. These observations suggest that 29% of patients undergoing apparently curative resection for colorectal carcinoma possess occult hepatic metastases and that computed tomography is superior to ultrasonography and isotope liver scan in detecting them.     

18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

Background

Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery.

Methods

From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy.

Results

156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490).

Conclusion

In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery.     

Follow-up computed tomography in patients operated on for liver malignancies

The aim of the investigation was to study a role of computed tomography (CT) in choosing treatment policy for patients after hepatectomy. In 186 patients with liver malignancies, 558 follow-up studies were performed 3 months to 8 years after surgery and adjuvant treatment. RESULTS: the permanent change of the liver, which is detectable at postoperative CT, is its outline deformity. Inverted (87%), irregular (56%), and, less frequently, convex (13%) outlines were identified. Among 41 patients who had postoperatively undergone adjuvant chemoembolization, 7 (17%) patients were seen to have a local compact lipidiol concentration adjacent to the resection plane. CT carried out in 19 patients with suspected postoperative complications could recognize the cause of complications (liver abscesses, abdominal fluid, bilomas) in 15 (78.9%) cases. In 20 patients, compact lipidiol accumulation in the vicinity of the resection plane was the most common, but not pathognomonic sign of tumor resection in the resection plane. Thus, CT plays an important role in the follow-up of patients after liver resections for malignancies in both the early and late postoperative periods.     

Arginase as a useful factor for the diagnosis of colorectal cancer liver metastases

The present work is a continuation of studies on arginase as a marker in the diagnosis of colorectal cancer liver metastases (CRCLM). The purpose of the study was the evaluation of the arginase test in comparison with other colorectal cancer tests such as CEA, CA 19-9 and biochemical markers of liver function such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The studies were conducted on blood serum from 85 patients with CRCLM obtained one to two days before tumor resection. The control group comprised 140 healthy blood donors and 81 patients with various non-malignant gastrointestinal diseases. Raised arginase activity was observed in serum of 85% of CRCLM patients, whereas elevated levels of CEA and CA 19-9 were found in 63% and 42% of patients, respectively. The combination of CEA or CA 19-9 with the arginase assay improved their sensitivity, but the sensitivity of the combined parameters was not higher than that of the arginase test itself. AST and ALT activities were increased in about 30% of CRCLM patients. The specificity of the arginase test calculated for 221 control subjects was 76%. It can thus be concluded that the determination of serum arginase activity can be helpful in the diagnosis of patients with colorectal cancer liver metastases.     

Liver Resection for Non-Colorectal,Non-Carcinoid,Non-Sarcoma Metastases: A Multicenter Study

Background

The role of liver resection for non-colorectal, non-neuroendocrine, non-sarcoma (NCNNNS) metastases is ill-defined. This study aimed to examine the oncologic outcomes of liver resection in such patients.

Methods

A retrospective analysis of liver resection for NCNNNS metastases was performed at two large centers. Liver resection was offered selectively in patients with stable disease. Oncologic outcomes were examined using the Kaplan-Meier method.

Results

Fifty-two patients underwent liver resection for NCNNNS metastases. Overall 5-year survival was 58%. Five-year survival was 85% for breast metastases, 66% for ocular melanoma, 83% for other melanomas, 50% for gastro-esophageal metastases, and 0% for renal cell carcinoma metastases. A contemporary colorectal liver metastasis cohort had a survival of 63% (p=0.89).

Conclusions

Liver resection is an effective option in the management of selected patients with NCNNNS metastases which have been deemed stable. Five-year survival rates were comparable to that of a contemporary cohort of patients with colorectal liver metastases in carefully selected patients. Further, larger studies are required to help identify potential prognostic variables and aid in decision-making in this heterogeneous population.     

Role of carcinoembryonic antigen in detection of asymptomatic disseminated disease in colorectal carcinoma.

Fifty one patients were studied prospectively to evaluate the role of sequential determinations of the carcino-embryonic antigen concentration in the detection of asymptomatic disseminated disease after curative resection for colorectal carcinoma. Computed tomography of the liver was performed during the immediate postoperative period in all patients. Serum concentrations of the antigen were estimated at three month intervals for a minimum of two years. Computed tomography at the time of operation detected occult hepatic metastases in 12 patients. Of the remaining 39 patients, six developed local recurrence alone, two developed disseminated disease in the absence of hepatic metastases, and one developed hepatic disease at 10 months, as detected by sequential computed tomography. Of all 13 patients with asymptomatic hepatic metastases, only eight developed an increase in serum carcinoembryonic antigen concentrations before death. The median interval between detection by computed tomography and rise in antigen concentrations was 7.5 months. The corresponding median interval from increase in concentration to death was only 5.5 months. Of the six patients who developed local recurrence alone, only two had raised concentrations of the antigen. These results suggest that increase in the serum carcinoembryonic antigen concentration occurs late in colorectal carcinoma.     

Laparoscopic versus Open Hepatectomy with or without Synchronous Colectomy for Colorectal Liver Metastasis: A Meta-Analysis

Background

To compare short-term and long-term results of colorectal patients undergoing laparoscopic and open hepatectomy. Moreover, outcomes of laparoscopic versus open procedures for simultaneous primary colorectal tumor and liver metastasis resection were compared.

Methods

A systematic search was conducted in the PubMed and EmBase databases (until Oct. 22. 2013) with no limits. Bibliographic citation management software (EndNote X6) was used for extracted literature management. Quality assessment was performed according to a modification of the Newcastle-Ottawa Scale. The data were analyzed using Review Manager (Version 5.1), and sensitivity analysis was performed by sequentially omitting each study.

Results

Finally, 14 studies, including a total of 975 CLM (colorectal liver metastasis) patients, compared laparoscopic with open hepatectomy. 3 studies of them, including a total of 107 CLM patients, compared laparoscopic with open procedures for synchronous hepatectomy and colectomy. Laparoscopic hepatectomy was associated with a significantly less blood loss, shorter hospitalization time, and less operative transfusion rate. In addition, lower hospital morbidity rate (OR = 0.57, 95%CI:0.42–0.78, P = 0.0005) and better R0 resection (OR = 2.44, 95%CI:1.21–4.94, P = 0.01) were observed in laparoscopic hepatectomy. For long-term outcomes, there were no significant differences between two surgical procedures on recurrence and overall survival. In comparison of synchronous hepatectomy and colectomy, laparoscopic procedure displayed shorter hospitalization (MD = −3.40, 95%CI:−4.37–2.44, P<0.00001) than open procedure. Other outcomes, including surgical time, estimated blood loss, hospital morbidity, and overall survival did not differ significantly in the comparison.

Conclusions

Laparoscopic hepatectomy with or without synchronous colectomy are acceptable for selective CLM patients. We suggest standard inclusion criteria of CLM patients be formulated.