Recurrence at surgical margin following hepatectomy for colorectal liver metastases is not associated with R1 resection and does not impact survival

BackgroundResection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival.MethodsClinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined.ResultsDuring the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001).ConclusionThe incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases.     

Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases

BACKGROUND: The aim of this study was to examine the relationship between surgical margin status and site of recurrence after potentially curative liver resection for colorectal metastases using an ultrasonic dissection technique. METHODS: Between January 2000 and December 2003, 176 patients underwent liver resection with curative intent for colorectal metastases at a single institution. Demographics, operative data, pathological margin status, site of recurrence and long-term survival data were collected prospectively and analysed. RESULTS: On pathological analysis, resection margins were positive in 43 patients, negative by 1-9 mm in 110, and clear by more than 9 mm in 23 patients. At a median follow-up of 33 months, 133 of 176 patients had developed a recurrence, only five of whom had recurrence at the surgical margin. Recurrence at the surgical margin was not significantly related to the size of the margin. Overall, the median time to recurrence was 12.6 months, which was independent of surgical margin size, although there was a significantly higher proportion of patients with multiple metastases in the group with a positive margin (P = 0.008). Margin status did not correlate significantly with either recurrence-free or overall survival. CONCLUSION: The rate of recurrence at the surgical margin was low and a positive margin was not associated with an increased risk of recurrence either at the surgical margin or elsewhere.     

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

Background

Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.

Methods

Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.

Results

The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.

Conclusions

Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.     

Resection of Colorectal Liver Metastases: Is a Resection Margin of 3 mm Enough?

Background

A safety margin of ≥10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in this distance.

Methods

A total of 333 patients were included in a multicenter trial after resection of colorectal liver metastases. Dissection of the liver had been performed with a CUSA^®, UltraCision^®, or water-jet dissector. The size of the resection margin was correlated with recurrence risk and survival.

Results

The median hepatic recurrence-free survival reached 35 months for all patients; median recurrence-free survival was 24 months and overall survival was 41 months. Univariate analysis of different groups denoting the extent of resection margin (≥10 mm, 6–9 mm, 3–5 mm, 1–2 mm, 0 mm (R1)) indicated that a margin of 1–2 mm leads to a significantly reduced median hepatic recurrence-free survival of 20 months (p = 0.004) and recurrence-free survival of 19 months (p = 0.011). Patients with R1 resection had the worst prognosis. Overall survival was not influenced by the size of the resection margin. Surgical margins were significantly reduced in simultaneous resections of four or more liver metastases and in cases in which metastatic infiltration of central liver segments was present. At multivariate analysis, resection margins of 1–2 mm and 0 mm were independent predictors of hepatic recurrence and overall recurrence.

Conclusion

The indication for resection of metastases can be safely extended to cases in which tumors sit closer than 1 cm to nonresectable structures.     

Cryosurgery of close or positive margins after hepatic resection for primary and metastatic hepatobiliary malignancies

Obtaining a one-centimeter negative margin is an important factor in preventing disease recurrence after surgery for hepatic tumors. Cryotherapy of the resected edge has been used to achieve optimal margin clearance in cases in which the alternative would be an extended high-risk liver resection. The effect of this technique on margin recurrence was examined. Between 1994 and 2001 a total of 56 patients underwent cryosurgery with or without resection for primary and metastatic hepatobiliary malignancies. A 5-cm cryotherapy lollipop probe was used to ablate surgical margins less than one centimeter in 13 of these patients. There were seven colorectal metastases, three hepatocellular carcinomas, and three gallbladder carcinomas. The median size of the colorectal and hepatocellular lesions was 3 cm (range 2-14 cm), and all gallbladder primaries were T2 tumors. All tumors except three were located centrally in the liver requiring cryoablation of margins at segments 4, 5, and 8. Most patients had one site frozen (n = 9) with a median target temperature of -190 degrees C and a median of two freeze-thaw cycles. Final pathological analysis of the resected specimens revealed nine close (<1 cm) and four positive margins. With a median follow-up of 16 months seven patients are alive with no evidence of disease and six have developed recurrences with three of them dying of their disease. Only one (8%) of the initial recurrences was at the cryoablated margin. Cryosurgery of the resection edge facilitates liver resection for malignant tumors when margins are close or positive. Because disease recurrence at the cryoablated margin is low this technique may allow more patients to undergo effective surgical treatment of their hepatobiliary cancers.     

Treatment strategy for hepatic metastases of colorectal cancer

Over the past 25 years, 125 patients with colorectal liver metastases underwent 167 hepatectomies in our department. The 1-, 3-, and 5-year survival rates after the initial hepatectomy were 90%, 58%, and 51%, respectively, and those after repeated hepatectomy were 88%, 60%, and 42%, respectively. The predictive factors significantly associated with poor prognosis after initial hepatectomy were maximal diameter of metastasis (> or = 5 cm), distribution pattern in the liver (multiple bilobar), number of nodules (> or = four), and presence of extrahepatic metastases. A disease-free interval of > 6 months after initial hepatectomy was a significant factor for prolongation of survival after repeat hepatectomy. Patients with hilar node metastases at the initial hepatectomy did not receive a survival benefit from hepatectomy, while 5 patients underwent repeat hepatectomy with lymphadenectomy for remnant liver and hilar node metastases with a disease-free interval of > 8 months and 4 of them survived for > 5 years. Our treatment strategies for colorectal hepatic metastases are as follows: 1) hepatectomy is the first choice for < 4 liver metastases without extrahepatic disease; 2) a careful evaluation for liver resection is performed for patients with > or = 4 liver metastases receiving hepatic arterial infusion chemotherapy because of the high frequency of hepatic and/or extrahepatic recurrence after initial hepatectomy; 3) the presence of hilar node metastases at the initial hepatectomy should be excluded from surgical indications; 4) simultaneous single metastasis limited to the lung is an indication for lung resection; and 5) a suitable indication for repeat hepatectomy for hepatic recurrence is patients with a longer disease-free interval. Aggressive surgery based on the optimum patient selection can contribute to clinical benefit, including long-term survival in patients with colorectal liver metastases.     

Treatment of adrenal metastases after hepatic resection of a hepatocellular carcinoma

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not been well characterized. METHODS: Of 562 patients who underwent hepatic resection for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years at the time of hepatic resection). RESULTS: The mean diameter of the primary tumors was 5 cm, and all were located in the right lobe of the liver. The mean interval from hepatic resection to recurrence was 18 months. Seven patients underwent treatment of intrahepatic recurrence. To treat the adrenal metastases, surgical resection was performed in 4 patients, and transcatheter arterial embolization was performed in 1 patient. The patients treated had no other extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6 cm. There was no hospital mortality. With surgical resection, 1 patient has been alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often large at the time of diagnosis. Since surgical resection was a safe procedure, and some patients could be alive for a long time, it should be performed whenever possible.     

Survival after hepatic resection for malignant tumours.

A retrospective analysis of 194 patients who underwent hepatic resection for primary or metastatic malignant disease from January 1962 to December 1988 was undertaken to determine variables that might aid the selection of patients for hepatic resection. Hepatic metastases were the indication for resection in 126 patients. The 5-year survival rate was 17 per cent. For patients with resected metastases from colorectal cancer (n = 104), the survival rate at 5 years was 18 per cent. The 5-year survival rate was 27 per cent when the resection margin was > 5 mm compared with 9 per cent when the margin was < or = 5 mm (P < 0.01). No patient with extrahepatic invasion, lymphatic spread, involvement of the resection margin or gross residual disease survived to 5 years, compared with a 23 per cent 5-year survival rate for patients undergoing curative resection (P < 0.02). The survival rate of patients with poorly differentiated primary tumours was nil at 3 years compared with a 20 per cent 5-year survival rate for patients with well or moderately differentiated tumours (P not significant). The site and Dukes' classification of the primary tumour, the sex and preoperative carcinoembryonic antigen level of the patient, and the number and size of hepatic metastases did not affect the prognosis. The 5-year survival rate for patients with hepatocellular carcinoma (n = 42) was 25 per cent. An improved survival rate was found for patients whose alpha-fetoprotein level was normal (37 per cent at 5 years) compared with those having a raised level (nil at 3 years) (P < 0.01). Involvement of the resection margin, extrahepatic spread and spread to regional lymph nodes were associated with an 8 per cent 5-year survival rate versus 44 per cent for curative resection (P < 0.005). The presence of cirrhosis, the presence of symptoms, and the multiplicity and size of the tumour did not affect the prognosis. The 5-year survival rate of 11 patients with hepatic sarcoma was 25 per cent. No patient with peripheral cholangiocarcinoma survived to 1 year in contrast to patients with hilar cholangiocarcinoma, all four of whom survived for more than 14 months.     

Recurrence Location After Resection of Colorectal Liver Metastases Influences Prognosis

Aim

To assess the impact of first recurrence location on survival following surgery of colorectal liver metastases.

Methods

A total of 265 consecutive patients with colorectal liver metastases undergoing liver surgery (2000–2011) were categorized according to first site of tumor recurrence. Time to recurrence (TTR) and overall survival (OS) were determined. Uni- and multivariate analysis were performed to identify factors associated with TTR and OS.

Results

Median TTR was 1.16 years following liver resection, and 0.56 years following radiofrequency ablation (RFA). Intrahepatic recurrence following liver resection resulted in a significantly shorter median TTR compared to extrahepatic recurrence. Intrapulmonary recurrence was associated with superior survival compared to other recurrence locations. Such patterns were not observed in the RFA-treated group. Multivariate analysis identified the type of surgical treatment and extra-hepatic first-site recurrence (other than lung) as independent predictors for OS. Pre-operative chemotherapy and simultaneous intrahepatic and extrahepatic recurrence were independent predictors for both TTR and OS.

Conclusions

Patients with intrahepatic recurrence following liver resection have a significantly shorter TTR and OS when compared to patients developing extrahepatic recurrence. Pulmonary recurrence following resection is associated with longer survival. Simultaneous intra- and extrahepatic recurrence is an independent prognostic factor for TTR and OS.     

影响结直肠癌肝转移手术切除患者预后的多因素分析

目的 探讨影响结直肠癌肝转移患者手术切除的预后因素。方法 收集1995-2001年间收治的结直肠癌肝转移手术切除患者103例的资料，用Kaplan-Meier法计算术后生存率，以Cox模型进行多变量分析。结果 患者术后1、3年无瘤生存率分别为73．8％和43．7％，术后1、3年累积生存率分别为7g．6％和49．5％。单因素分析显示：术前血清CEA水平、转移灶与原发灶的治疗间隔时间、术中切缘情况、肝门淋巴结转移、肝内卫星灶的存在与否、肝转移灶的最大直径、数目及有无包膜影响患者的术后肝内复发和术后累积生存率，而术后化疗可以提高患者的累积生存率。多因素分析显示：转移灶与原发灶的治疗间隔时间、切缘情况、肝内卫星灶的存在与否和肝转移灶的最大直径是影响肝内复发和累积生存率的独立因素，而肝门淋巴结转移是影响累积生存率的独立因素，有无包膜是影响肝内复发的独立因素。结论 手术切除是结直肠癌肝转移有效的治疗手段。转移灶与原发灶的治疗间隔时间、切缘情况、肝内卫星灶、肝转移灶的大小和包膜、肝门淋巴结转移等是患者预后的独立影响因素。     

Management of involved or close resection margins in 120 patients with colorectal liver metastases: edge cryotherapy can achieve long-term survival

BACKGROUND: The liver resection margin is prognostically significant for patients with colorectal liver metastases. Management plans for patients with suboptimal resection margins have not been adequately addressed. This article reports the long-term results of edge cryotherapy in 120 patients with suboptimal resection margins. METHODS: A retrospective analysis of prospectively collected clinical data of 120 patients with suboptimal hepatic resection margins was performed. Morbidity, mortality, recurrence, and survival results were analyzed. RESULTS: The median length follow-up was 30 months (range 1 to 139). The median disease-free interval was 19 months (range 2 to 139). Cryosite, remaining liver, and extrahepatic recurrence rates were 10%, 36%, and 47%, respectively. The median survival was 39 months (range 1 to 139), and 1-, 3-, and 5-year survival rates were 89%, 55%, and 36%, respectively. Cryosite and extrahepatic recurrence were independently associated with a reduced survival outcome. COMMENTS: Edge cryotherapy to suboptimal liver resection margins can achieve a lower local recurrence rate and a longer survival advantage.     

The Significance and Clinical Factors Associated With a Subcentimeter Resection of Colorectal Liver Metastases

Background Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse.Methods Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR.Results A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002).Conclusions A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Reduction in recurrence risk for involved or inadequate margins with edge cryotherapy after liver resection for colorectal metastases

HYPOTHESIS: The usefulness of additional edge cryotherapy after liver resection for liver metastases from colorectal cancer to improve involved or inadequate (less than 1 cm) margins is uncertain. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of surgery at a university hospital. PATIENTS: Eighty-six consecutive patients with hepatic metastases from colorectal cancer in whom we applied additional edge cryotherapy to involved or inadequate margins. This group was compared with 134 patients who underwent resection without edge cryotherapy (control group) during the same period. INTERVENTION: Potentially curative treatment was achieved by adding edge cryotherapy to insufficient resection sites in patients not eligible for further resection. MAIN OUTCOME MEASURES: Edge recurrence rate in the study group; validation of an additional treatment to improve curative resectability; and comparison of morbidity and local recurrence rates with the control group. RESULTS: At a median follow-up of 39 months, 47 patients were alive and 39 had died. Local recurrence at the resection site was diagnosed in 9 patients (10%), of which 7 occurred in patients with involved margins and 2 in patients with resection margin less than 1 cm. Thirty-six patients (42%) experienced recurrence in the remnant liver. Extrahepatic recurrence occurred in 38 patients (44%), the lungs being the most common site (22 patients [26%]). CONCLUSIONS: Edge cryotherapy is a potent additional surgical treatment option in patients with liver metastases from colorectal cancer. The percentage of patients who can be treated for cure can be increased, especially if complex liver surgery is demanded.     

Resecting large numbers of hepatic colorectal metastases

Background : Despite the widespread use of surgical resection as a treatment for hepatic colorectal metastases, the value of resecting more than three metastases remains controversial. It was the objective of this study to determine if resection of larger numbers of metastases affects patient survival. Method : The survival of 123 consecutive patients who underwent curative hepatic resection for colorectal metastases between 1989 and 1999 by a single surgeon was analysed retrospectively. Kaplan–Meier survival statistics and Cox regression were used to determine the factors that affected survival, and logistic regression was used to determine the factors that affected the risk of recurrence of hepatic disease. Results : The median survival rate for the whole group of patients was 38 months, with 1, 3 and 5 year survival rates of 88%, 53% and 31% respectively. The survival rate of patients undergoing resection of four to seven metastases (n = 22; 5 year survival = 39%) was not significantly different to that of patients undergoing resection of one to three metastases (n = 91; 5 year survival = 30%), P = 0.9. Age, sex, primary cancer site, hepatic disease distribution, resection margins and adjuvant hepatic arterial chemotherapy (HAC) did not affect survival. Local invasion of the hepatic metastases (relative risk (RR) = 2.9; P = 0.001) and hepatic disease recurrence (RR = 2.1; P = 0.007) were the only factors that independently affected survival. Local invasion of the hepatic metastasis was the only factor associated with an increased risk of hepatic recurrence (RR = 2.8; P = 0.03). Adjuvant HAC did not affect the risk of hepatic recurrence (RR = 1.5, P = 0.4). Conclusion : Although there are no randomized trials that quantify any survival benefit from resection of liver metastases, the comparison of our results with well documented historical evidence indicates that surgical resection of up to seven colorectal liver metastases can result in a significant survival benefit.     

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.     

Indicators of prognosis after hepatic resection for colorectal secondaries.

From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding "high risk" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control.     

Histopathologic excision margin affects local recurrence rate: analysis of 2681 patients with melanomas < or =2 mm thick

OBJECTIVE: Prospective trials have shown that 1-cm and 2-cm margins are safe for melanomas <1 mm thick and > or =1 mm thick, respectively. It is unknown whether narrower margins increase the risk of LR or mortality. SUMMARY BACKGROUND DATA: To determine the relationship between histopathologic excision margin, local recurrence (LR) and survival for patients with melanomas < or =2 mm thick. METHODS: Data were extracted from the Sydney Melanoma Unit database for all patients with cutaneous melanoma < or =2 mm thick, diagnosed up to 1996. Patients with positive excision margins or follow-up <12 months were excluded, leaving 2681 for analysis. Outcome measures were LR (recurrence <5 cm from the excision scar), in-transit recurrence, and disease-specific survival. Factors predicting LR and overall survival were tested with Cox proportional hazards analysis. RESULTS: Median follow-up was 83.8 months. LR was identified in 55 patients (median time to recurrence, 37 months). At 120 months, the actuarial LR rate was 2.9%. Five-year survival after LR was 52.8%. In multivariate analysis, only margin of excision and tumor thickness were predictive of LR (both P = 0.003). When all patients with a margin <0.8 cm in fixed tissue (corresponding to a margin of <1 cm in vivo) were excluded from analysis, margin was no longer significant in predicting LR. Thickness, ulceration, and site were predictive of survival, but margin was not (P = 0.49). CONCLUSIONS: Histopathologic margin affects the risk of LR. However, if the in vivo margin is > or =1 cm, it no longer predicts risk of LR. Patient survival is not affected by margin.     

CRYOTHERAPY OF THE RESECTION EDGE AFTER LIVER RESECTION FOR COLORECTAL CANCER METASTASES

Background : An involved or inadequate (< 1 cm) resection margin is associated with a high rate of local tumour recurrence and reduced survival rates after liver resection for colorectal metastases. This paper assesses whether or not hepatic cryotherapy of the resection edge is suitable to improve local disease control. Methods : From April 1990 to May 1997, we performed cryotherapy of the resection edge in 44 patients after liver resection for colorectal liver metastases with an involved or inadequate resection margin. The reasons for performing edge cryotherapy instead of extension of resection were: proximity of hepatic veins or portal sheath (n= 12); avoidance of extended left or right hemihepatectomy (n= 15); inadequate liver tissue reserve after resection (n= 16); and patient unfit to undergo further major resection (n= 1). Histological examination showed the resection margin to be involved in 24 patients and close (< 1 cm) in 20 patients. Results : Two patients died after surgery. Morbidity consisted of intra-abdominal collections (n= 6), postoperative bleeding (n= 1), wound infection (n= 1) and transient liver failure (n= 1). At a median follow-up of 19 months, 16 patients are alive and disease-free, 26 patients developed recurrence and 15 of them died. Nineteen patients developed recurrence which involved the liver but only five of these were at the resection edge. Median overall and liver disease-free survival was 33 and 23 months, respectively. Conclusions : Cryotherapy of the resection edge after resection of colorectal liver metastases with involved or inadequate resection margins considerably improves local disease control and may allow a greater proportion of patients with liver metastases to undergo potentially curative treatment.     

Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy

Background Hepatic resection is generally accepted as the only potential for long-term survival in patients with colorectal metastases confined to the liver. Despite an unknown benefit, hepatic resection is playing an increasing role in patients with extensive disease. Methods A retrospective review of a prospectively maintained hepatobiliary surgical database was carried out. Outcome after hepatectomy for four or more colorectal hepatic metastases was reviewed. Results Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with four or more colorectal hepatic metastases were resected. Actuarial 5-year survival was 33% for the entire group, with seven actual 5-year survivors. There were no perioperative deaths, and the perioperative morbidity was 28%. Positive margins and extrahepatic disease resection were independently associated with poor outcome. The median disease-free survival was 12 months, with no actuarial disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant chemotherapy, time to recurrence, and resection of recurrent disease were also associated with outcome. Conclusions Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary.     

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

OBJECTIVE: To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. BACKGROUND: Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. METHODS: Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. RESULTS: Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. CONCLUSION: PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.