Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy

OBJECTIVE: To investigate whether sinusoidal injury (SI) was associated with a worse outcome after hepatectomy in patients with colorectal liver metastases (CRLM). BACKGROUND: Correlation between SI and oxaliplatin-based chemotherapy (OBC) was recently shown in patients with CRLM. However, it has yet to be fully clarified whether SI affects liver functional reserve and outcome after hepatectomy. PATIENTS AND METHODS: Between 2003 and 2005, 90 patients with CRLM who underwent an elective hepatectomy after preoperative chemotherapies were included. Diagnosis of SI was established pathologically in the nontumoral liver parenchyma of the resected specimens, and perioperative data were assessed in these patients. RESULTS: OBC was significantly associated with a higher incidence of SI. Preoperative indocyanine green retention rate at 15 minutes (ICG-R15) and postoperative value of total-bilirubin were significantly higher, and hospital stay was significantly longer in patients presenting with SI. Multivariate analysis showed that female gender, administration of 6 cycles or more of OBC, abnormal value of preoperative aspartate aminotransferase >36 IU/L, or abnormal value of preoperative ICG-R15 (>10%) were preoperative factors significantly associated with SI. Among patients undergoing a major hepatectomy, SI was significantly associated with higher morbidity and longer hospital stay. CONCLUSION: The present study suggests that SI resulted in a poorer liver functional reserve and in a higher complication rate after major hepatectomy. Therefore, female patients who received 6 cycles or more of OBC, or presenting with abnormal preoperative aspartate aminotransferase and ICG-R15 values should be carefully selected before deciding to undertake a major hepatectomy.     

Repeat hepatectomy for colorectal liver metastases

This study includes 16 patients (9 men, 7 women; mean age 64 years) who underwent a total of 19 repeat hepatectomies for metastasis after colon (n=7) or rectal (n=9) carcinoma. All patients were reoperated for recurrent liver metastasis after the first resection (mean, 21 months; range, 7-40 months), and three had a third hepatectomy 13, 24, or 65 months after the second. Perioperative mortality was 0% and morbidity was 37%. The 3- and 5-year survival rates after the second resection were 56.8% and 28.4%, respectively, with a median survival of 42.3 months. Seven patients died (mean survival, 25.7 months; range, 9-58 months) before the end of the study. Six patients were alive with one or more recurrences, and three (24, 51, and 173 months of follow-up) were alive without known recurrence. Survival rates for repeat resections of colorectal liver metastases in selected patients were comparable with those obtained after resection of a first liver metastasis.     

大肠癌肝转移术前化疗后的最佳手术时机

化疗联合手术治疗已逐渐成为结直肠癌肝转移病人的标准治疗方式。对于可切除的大肠癌肝转移病人是否需要术前化疗仍存在争议。存在预后不良因素时应接受术前化疗,术前化疗不应＞6周期。不可切除的肝转移病人均应接受术前化疗,术前化疗后定期复查,如转化为可切除,应立即切除。一般认为,停用化疗4周后可以手术切除肝转移灶,但如果联合贝伐单抗,应在停止治疗6~8周后进行手术。     

Repeat hepatectomy for colorectal liver metastases.

OBJECTIVE: The authors assess the long-term results of repeat hepatectomies for recurrent metastases of colorectal cancer and determine the factors that can predict survival. SUMMARY BACKGROUND DATA: Safer techniques of hepatic resection have allowed surgeons to consider repeat hepatectomy for colorectal metastases in an increasing number of patients. However, higher operative bleeding and increased morbidity have been reported after repeat hepatectomies, and the long-term benefit of these procedures needs to be evaluated. STUDY POPULATION: Sixty-four patients from a group of 243 patients resected for colorectal liver metastases were submitted to 83 repeat hepatectomies (64 second, 15 third, and 4 fourth hepatectomies). Combined extrahepatic surgery was performed in 21 (25%) of these 83 repeat hepatectomies. RESULTS: There was no intraoperative or postoperative mortality. Operative bleeding was not significantly increased in repeat hepatectomies as compared to first resections. Morbidity and duration of hospital stay were comparable to first hepatectomies. Overall and disease-free survival after a second hepatectomy were 60% and 42%, respectively, at 3 years and 41% and 26%, respectively, at 5 years. Factors of prognostic value on univariate analysis included the curative nature of first and second hepatectomies (p = 0.04 and p = 0.002, respectively), an interval between the two procedures of more than 1 year (p = 0.003), the number of recurrent tumors (p = 0.002), serum carcinoembryonic antigen levels (p = 0.03), and the presence of extrahepatic disease (p = 0.03). Only the curative nature of the second hepatectomy and an interval of more than 1 year between the two procedures were independently related to survival on multivariate analysis. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies, with no mortality and comparable morbidity. Combined extrahepatic surgery can be required to achieve tumor eradication. Repeat hepatectomies appear worthwhile when potentially curative.     

Impact of repeat hepatectomy on recurrent colorectal liver metastases

BACKGROUND. Hepatic recurrence is seen in approximately 40% of patients undergoing hepatectomy for colorectal metastases. This study was designed to assess the risks and clinical benefits of repeat hepatectomy for those patients. METHODS. Twenty-six patients underwent repeat hepatectomy for hepatic recurrence, and their clinical data were retrospectively reviewed for operative morbidity and mortality, performance level, and survival. RESULTS. There was no operative mortality after repeat hepatectomy. Operative bleeding was significantly increased in the second hepatectomy; but operating time, duration of hospital stay, and performance status after the second hepatectomy were comparable with those of the initial hepatectomy. The median survival time from the second hepatectomy was 31 months, and the 3- and 5-year survival rates were 62% and 32%, respectively. A short disease-free interval (6 months or less) between the initial hepatectomy and diagnosis of hepatic recurrence in the remnant liver was significantly associated with poor survival after the second hepatectomy. CONCLUSIONS. Repeat resection contributed to clinical benefits for selected patients with hepatic recurrence after the initial hepatectomy for colorectal liver metastases. However, appearance of hepatic recurrence within 6 months or less after the initial hepatectomy is a poor prognostic factor for repeat hepatectomy.     

Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases

BACKGROUND: We investigated perioperative complications of hepatic arterial infusion chemotherapy preceding major hepatectomy for multiple bilobar colorectal cancer metastases. No consensus exists concerning operative feasibility or perioperative course in patients undergoing major liver resection with neoadjuvant chemotherapy--partly because such chemotherapy is considered hepatotoxic, increasing the risk of postoperative liver failure. METHODS: Clinicopathologic data were available for 41 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent major liver resection with or without prior hepatic arterial chemotherapy. Data concerning operative feasibility, postoperative liver function, complication rates, and histologic findings in the non-neoplastic liver were analyzed retrospectively. RESULTS: Prehepatectomy and postoperative day 1 platelet counts were lower (P < .01 and P < .05), alkaline phosphatase on postoperative day 3 was higher (P < .01), and prothrombin time on day 1 was more prolonged (P < .01) in the chemotherapy group. No significant difference was seen between groups in intraoperative data, morbidity, or duration of hospitalization. Histologic examination of adjacent non-neoplastic liver confirmed mild to severe fatty degeneration in 91% of the patients undergoing neoadjuvant chemotherapy, compared with 53% in those without neoadjuvant chemotherapy (P = .023). Although the number of neoplasms in chemotherapy patients was greater than that of the other group, overall and disease-free survival rates were comparable between groups. CONCLUSIONS: Despite mild postoperative liver dysfunction, pre-resection hepatic arterial chemotherapy did not increase morbidity.     

Influence of pre-surgical chemotherapy on liver parenchyma and post-surgical outcome of patients subjected to hepatectomy due to colorectal carcinoma metastases

IntroductionThe aim of the study was to evaluate the relationship between the pre-surgical administration of a chemotherapy regime based on irinotecan or oxaliplatin and the development of non-alcoholic fatty liver disease (NAFLD) or sinusoidal obstruction syndrome (SOS), and the influence of these histological changes on the outcome of patients after surgical intervention.Patients and methodA prospective study which included 45 patients surgically intervened due to colorectal cancer liver metastases between May 2005 and July 2009. Demographic data and the variables before during and after the operation were collected. A specimen of the resection was obtained for histological analysis following the classification parameters of the NAFLD (NASH index) and SOS scale.ResultsNeoadjuvant chemotherapy was given before the resection in 22 cases (study group) and 23 patients made up the control group (no chemotherapy). Borderline or diagnostic steatohepatitis was observed in 4 of the 7 patients (57.2%) who were given preoperative irinotecan (P=0.001). Seven of the 15 patients (46.7%) treated with oxaliplatin developed a moderate or severe SOS (P=0.002). There were no differences in morbidity or mortality associated to the NAFLD grade, but there was a higher rate of liver complications and longer mean hospital stay in patients with moderate/severe SOS (P=0.004 and P=0.021, respectively).ConclusionsTreatment with irinotecan was significantly associated with an increase in the incidence of steatohepatitis, but did not increase the morbidity or mortality. Patients treated with oxaliplatin had a higher incidence of SOS, an increase in liver complications and a longer mean hospital stay.     

精准肝切除在结直肠癌肝转移中的应用价值

目的 探讨精准肝切除在结直肠癌肝转移治疗中的应用价值.方法 回顾性分析2006年10月至2009年10月天津医科大学附属肿瘤医院收治的85例结直肠癌肝转移患者的临床资料.根据治疗方法分为常规组43例和精准组42例.常规组:术前常规检测评估肝肾功能,增强CT和B超检查评估肿瘤情况;根据术前检查结果行解剖性肝段切除.精准组:除常规组进行的各项检查外,还采用吲哚菁绿排泄试验评估肝脏储备功能;通过CT对肝动脉、肝静脉和门静脉进行三维重建,并测量肝脏体积及剩余肝脏体积;术中使用低中心静脉压;采用术中超声检查明确切除范围并保护好周围脉管结构,进行精确的解剖性肝段切除.观察比较两组患者术中、术后及预后的情况.计量资料采用t检验,计数资料采用x2检验.结果 两组患者均无围手术期死亡.常规组和精准组术中全肝血流阻断时间分别为(35±25)min和(64±39)min,出血量分别为(685±524)ml和(486±360)ml,两组比较,差异有统计学意义(t=4.116,-2.033,P＜0.05);术中输血量分别为(228±398)ml和(160±330)mJ,两组比较,差异无统计学意义(t=-0.861,P＞0.05).常规组和精准组患者术后第1天ALT分别为(672±284)U/L和(344±158)U/L,第7天ALT分别为(332±161)U/L和(125±93)U/L;住院时间分别为(18±10)d和(12±6)d;术后并发症发生率分别为26%(11/43)和7%(3/42),两组比较,差异有统计学意义(t=-6.541,-7.232,-3.915,x2=5.251,P＜0.05).常规组和精准组患者术后1年肝脏肿瘤复发率分别为37%(16/43)和21%(9/42);术后1年生存率分别为88%(38/43)和93%(39/42),两组患者预后比较,差异无统计学意义(x2=0.110,0.501,P＞0.05).结论 对于结直肠癌肝转移患者,精准肝切除较常规肝切除创伤小,恢复快,更加安全、有效.

Abstract：

Objective To evaluate precise hepatectomy for liver metastases of colorectal cancer. Methods The clinical data of 85 patients with liver metastases of colorectal cancer who were admitted to the Cancer Hospital of Tianjin Medical University from October 2006 to October 2009 were retrospectively analyzed. Forty-two patients received precise hepatectomy(precise group) and 43 received routine hepatectomy (routine group). Evaluation of the hepatic and renal functions and detection of the tumors' condition were done before carrying out anatomical liver resection for patients in the routine group. Hepatic functional reserve of patients in the precise group was detected by indocyanine green excretion test. Hepatic artery, hepatic vein and portal vein were three-dimensionally reconstructed according to the data of computed tomography. The liver volume and residual liver volume of the patients were calculated. Hepatic resection was guided by intra-operative ultrasound in the precise group. Periand postoperative conditions and the results of follow-up of patients in the two groups were compared. All data were analyzed using the t test or chi-square test. Results No perioperative mortality was observed in the two groups.Time of hepatic blood flow occlusion and blood loss were (35±25)minutes and (685 ± 524) ml in the routine group, and (64±39) minutes and (486±360) ml in the precise group, respectively, with a significant difference between the two groups(t=4.116,-2.033, P＜0.05). The volumes of blood transfusion of the routine group and the precise group were (228±398) ml and (160±330)ml, respectively, with no significant difference between the two groups (t=-0.861, P＞0.05). The postoperaive levels of alanine transaminase at day 1 and day 7 were (672±284)U/L and (332±161)U/L in the routine group, and (344±158)U/L and (125 ±93) U/L in the precise group, respectively, with a significant difference between the two groups (t=-6.541,-7.232,P＜0.05). The length of hospital stay and postoperative mobidity were (18±10)days and 26% (11/43) in the routine group, and (12±6)days and 7%(3/42) in the precise group, respectively, with a significant difference between the two groups (t=- 3.915, x2=5.251, P＜0.05). The 1-year tumor recurrence rate and 1-year survival rate were 37% (16/43) and 88% (38/43) in the routine group, and 21% (9/42) and 93% (39/42) in the precise group, with no significant difference between the two groups (x2= 0.110, 0. 501, P＞0.05). Conclusion Precise hepatectomy is superior to routine hepatectomy in aspect of minimal trauma, quick recovery, efficacy and safety.     

Early adjuvant intraportal chemotherapy after hepatectomy for metastases of colorectal origin

EAIPC was tested in a preliminary study, with continuous 600 mg/m2/day 5 FU with twelve consecutive patients after curative hepatectomies for colo-rectal metastases. The aim of this study is to reduce the frequency of recurrences inside the remaining liver. The numerous reasons explaining this kind of treatment are detailed. Results about technic problems and tolerance are analysed. This work should be initiate a prospective randomized study to evaluate the efficiency of the EAIPC.     

Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases

Background

Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated.

Methods

A prospective database over a 15‐year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy.

Results

Overall median survival in groups A and B were 36 (2–137) months and 33 (2–137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease‐free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high‐ and low‐risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings.

Conclusion

Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease‐free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.     

Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases

AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome.METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed.RESULTS: Fifty-three patients (50%) received surgery alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02).CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.     

The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases

HYPOTHESIS: The purpose of this study was to examine the validity of the clinical risk score (CRS), a prognostic tool developed by Fong et al, when translated to another center. DESIGN: This study assesses 5 independent preoperative prognostic criteria, nodal status of the primary lesion, disease-free interval, number of hepatic metastases, size of the largest metastasis, and preoperative carcinoembryonic antigen level, to determine a preoperative CRS for each patient included in the study. SETTING: The hepatobiliary unit of The Queen Elizabeth Hospital, Adelaide, South Australia. PATIENTS: Medical records of patients admitted to The Queen Elizabeth Hospital undergoing potentially curative hepatic resection for colorectal metastases during the period of July 1993 to April 2003 were included in the study.Main Outcome Measure The primary outcome measure of the study was survival. The calculated CRS was analyzed with respect to patient postoperative survival. RESULTS: During the 10-year period, 77 patients underwent hepatic resection. Overall survival rates for 1, 3, and 5 years were found to be 80.9%, 57.5%, and 42.3%, respectively. One- and 5-year survival rates for CRSs of 0 and 1 were found to be 93.8% and 72.5%, respectively; for scores of 2 and 3, 76.6% and 31.2%, respectively;and for scores of 4 and 5, 75% and 0%, respectively. No patient with a CRS greater than 3 survived more than 2 years. CONCLUSION: This study validates the CRS, finding it to be highly predictive of patient outcome and survival.     

Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases

BACKGROUND: Extrahepatic disease has always been considered an absolute contraindication to hepatectomy for liver metastases. The present study reports the long-term outcome and prognostic factors of patients undergoing resection of extrahepatic disease simultaneously with hepatectomy for liver metastases. METHODS: From January 1987 to January 2001, 111 (30 per cent) of 376 patients who had hepatectomy for colorectal liver metastases underwent simultaneous resection of extrahepatic disease with curative intent. RESULTS: Surgery was considered R0 in 77 patients (69 per cent) and palliative (R1 or R2) in 34 patients (31 per cent). The mortality rate was 4 per cent and the morbidity rate 28 per cent. After a median follow-up of 4.9 years, the overall 3- and 5-year survival rates were 38 and 20 per cent respectively. The 5-year overall survival rate of patients with R0 resection only (n = 75) was 29 per cent. The difference in survival between patients with and without extrahepatic disease discovered incidentally at operation was significant, as was the number of liver metastases. CONCLUSION: Extrahepatic disease in patients with colorectal cancer who also have liver metastases should no longer be considered an absolute contraindication to hepatectomy. However, the presence of more than five liver metastases and the incidental intraoperative discovery of extrahepatic disease remain contraindications to hepatic resection.