Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Background Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. Methods From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. Results One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). Conclusions Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. Presented at the Society for Surgery of the Alimentary Tract 48th Annual Meeting, May 2007, Washington, DC.     

Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Colorectal Liver Metastases Treated with Systemic Chemotherapy

Background  Whether neutrophil-to-lymphocyte ratio (NLR) predicts survival of patients with colorectal liver metastases (CLM) treated with systemic chemotherapy remains unclear. Methods  Clinicopathologic data were reviewed for patients with CLM treated with chemotherapy and resection (n = 200) or chemotherapy only (n = 90). Univariate and multivariate analyses for prognostic factors were performed. In the resection group, whether chemotherapy normalizes high NLR and the effect of NLR normalization on survival were evaluated. Results   In the resection group, patients with preoperative NLR > 5 had a worse 5-year survival rate than patients with NLR ≤ 5 (19% vs. 43%; P = 0.009), and NLR > 5 was the only independent preoperative predictor of worse survival (P = 0.016; hazard ratio [HR] = 2.22; 95% confidence interval [95% CI], 1.16–4.25). In the nonresection group, patients with prechemotherapy NLR > 5 had a worse 3-year survival rate than patients with NLR ≤ 5 (0% vs. 23%; P = 0.0002), and NLR > 5 was the only independent predictor of worse survival (P = 0.001; HR = 2.91; 95% CI, 1.54–5.50). In the resection group, chemotherapy normalized high NLR in 17 of 25 patients, and these 17 patients had better survival than the 8 patients with high NLR both before chemotherapy and before surgery (P = 0.021). Conclusion   NLR independently predicts survival in patients with CLM treated with chemotherapy followed by resection or chemotherapy only. When chemotherapy normalizes high NLR, improved survival is expected.     

Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

Two-Stage Resection for Bilobar Colorectal Liver Metastases: R0 Resection Is the Key

Background

Two-stage liver resection (2-SLR) is used clinically in conjunction with portal vein embolization for bilobar disease to increase the number of patients suitable for liver resection. The long-term outcomes after 2-SLR for multiple bilobar colorectal liver metastases (CLM) was examined.

Methods

Patients who sought care between November 2003 and April 2006 with multiple CLM considered suitable for 2-SLR were prospectively followed. Clinicopathological data were collected. Surgical outcomes were defined as complete clearance of tumor (R0/R1/R2), postoperative morbidity (within 3 months), 30 day mortality, disease-free survival (DFS), and overall survival (OS).

Results

A total of 131 patients with CLM underwent liver resection during the study period, 38 of whom were planned for a 2-SLR for multiple bilobar disease. Only 33 (87%) completed the 2-SLR with a curative intent. Five patients did not undergo stage II resection because of disease progression. The postoperative morbidity was 11 and 33% after stage I and stage II liver resections, respectively. Five patients (13%) encountered postoperative complications specific to liver surgery. The median interval from stage II resection to disease recurrence in the R0 group was 18 months versus 3 months in the R1/R2 group (P < 0.001). R0 resection with curative intent versus R1/R2 noncurative resection has a significantly longer period of DFS (P < 0.001) and OS (P = 0.04).

Conclusions

The 2-SLR combined with portal vein embolization is an effective and safe method for resecting previously unresectable multiple bilobar CLM. However, a positive resection margin leads to poor DFS and OS.

     

临界可切除肝癌行肝动脉灌注化疗联合肝动脉栓塞术转化治疗的疗效

背景与目的 对于临界可切除的原发性肝癌,目前我国原发性肝癌诊疗指南（2022年版）推荐仍是肝动脉插管化疗栓塞术（TACE）、外科手术切除或系统抗肿瘤治疗。当前原发性肝癌的术前转化治疗已经取得了很大的进展,但对于具体转化治疗方案尚在探索中。本研究探讨临界可切除肝癌行FOLFOX方案的肝动脉灌注化疗（HAIC）联合肝动脉栓塞术（TAE）局部转化治疗的真实世界疗效。方法 收集2019年4月—2022年2月采用FOLFOX方案的HAIC联合TAE转化治疗的22例临界可切除（CNLC分期Ⅱb期）原发性肝癌患者的临床资料,根据改良实体瘤疗效评价（mRECIST）标准评估肿瘤客观缓解率（ORR）、疾病控制率（DCR）,分析转化手术切除率和术后标本的病理缓解率以及转化治疗后手术与未手术患者的预后情况。结果 22例患者均完成HAIC联合TAE治疗,主要不良反应包括上腹痛、低热、短期的肝功能损害等,但没有发生不可逆的严重并发症。转化治疗后,肿瘤ORR、DCR分别为63.6%、86.3%,但有3例（13.6%）患者出现肿瘤进展。转化治疗结束后14例患者行肝癌手术切除,转化手术切除率为63.6%,手术顺利,均能达到R₀切除,无术后死亡病例。术后病理检查有10例（71.4%）为主要病理缓解（MPR）,但无1例能达到完全病理缓解（CPR）。14例手术患者的无复发生存期平均为14.7个月;手术患者的总生存期明显优于未手术患者（22.7个月vs. 13.2个月,P=0.018）。结论 HAIC联合TAE转化治疗对于临界可切除肝癌具有良好的耐受性,是安全可行的,能取得较高ORR、DCR和转化手术切除率。虽然大多数术前转化治疗后能达到MPR,但CPR较低,手术切除仍是肝癌转化治疗后患者获得长期生存的关键。     

Pathologic Response to Preoperative Chemotherapy in Colorectal Liver Metastases: Fibrosis, not Necrosis, Predicts Outcome

Background

Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown.

Methods

Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed.

Results

Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68?%) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46?%, P?P?P?=?.05) but similar rates of necrosis (30 vs. 31?%, P?=?.30). In patients receiving preoperative chemotherapy, overall pathologic response ??75?% (5?year, 83 vs. 47?%, P?P?P?=?.04) and bevacizumab (P?=?.05) were marginally associated with overall pathologic response and fibrosis, respectively.

Conclusions

Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.     

Extended Preoperative Chemotherapy Does Not Improve Pathologic Response and Increases Postoperative Liver Insufficiency After Hepatic Resection for Colorectal Liver Metastases

Background

The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM.

Methods

A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1–8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared.

Results

Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups.

Conclusions

Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.     

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.     

Favorable Outcome After Repeat Resection for Colorectal Liver Metastases

Background

The rate of recurrence after liver resection for colorectal liver metastases (CLM) is high, and repeat resection (RR) is reserved with curative intent in selected patients. This study evaluated the benefit of RR for recurrence after liver resection for CLM.

Methods

Data were collected on 287 consecutive patients who underwent primary curative hepatectomy between January 1999 and October 2008 for CLM at our institution.

Results

After median follow-up of 63 months, 211 patients (73 %) developed recurrence and RR was conducted in 102 (48 %) patients. Five-year overall survival (OS) was significantly higher in the RR group than in those patients not selected for RR (70 vs. 45 %, P = 0.002). On multivariate analyses, RR was identified as an independent factor for good prognosis. According to the first recurrence sites, 5-year OS after recurrence was significantly better in patients with liver or lung only recurrence (55, 51 %, respectively) than in locoregional/lymph node metastases and other/multiple sites recurrence (33, 9.0 %, respectively). In patients with liver- or lung-only recurrence, 5-year OS after recurrence was significantly higher in RR patients than in those without RR (liver; 67 and 0 %, lung; 88 and 24 %, respectively; P < 0.001).

Conclusion

Given similar indication criteria as the primary CLM, nearly half of all recurrence cases after liver resection for CLM could be salvaged by RR. In patients with liver-or lung-only recurrence, RR warrants a favorable outcome.     

Comparison of long-term survival outcome after curative hepatectomy between selected patients with non-colorectal and colorectal liver metastasis: A propensity score matching analysis

BackgroundLiver resection is an established treatment of choice for colorectal liver metastasis (CLM). However, the role of hepatectomy for non-colorectal liver metastasis (NCLM) is less clear.Patients and methodFrom 2004 to 2017, 264 patients received curative hepatectomy for NCLM (n = 28) and CLM (n = 236). Propensity score (PS) matching was performed between two groups, with respect to the significant confounding factors. Short-term and long-term outcomes were compared between PS matched groups. Univariate analysis was performed to identify prognostic factors affecting overall and recurrence-free survival.ResultsAfter PS matching, there were 28 patients in NCLM group and 56 patients in CLM group. With a median follow-up of 34 months, there was no significant difference in 5-year overall survival rate between NCLM and CLM groups (62% vs. 39%) (P = 0.370). The 5-year recurrence-free survival rate was also comparable between NCLM and CLM groups (23% vs. 22%) (P = 0.707). Use of pre-operative systemic therapy (hazard ratio: 2.335, CI 1.157–4.712), multifocal tumors (hazard ratio: 1.777, CI 1.010–3.127), tumor size (hazard ratio: 1.135, CI 1.012–1.273), R1 resection (hazard ratio: 2.484, CI 1.194–5.169) and severe complications (hazard ratio: 6.507, CI 1.454–29.124), but not tumor type (NCLM vs. CLM), were associated with poor overall survival.ConclusionHepatectomy for NCLM can achieve similar oncological outcomes in selected patients as those with CLM. Significant prognostic factors were identified associating with worse overall survival.     

Major Hepatectomy for Colorectal Metastases: Is Preoperative Portal Occlusion an Oncological Risk Factor?

Background  This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). Methods  Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. Results  21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. Conclusion  Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM. L. Mueller and C. Hillert contributed equally to this work.     

Chemotherapy With Bevacizumab Does Not Affect Liver Regeneration After Portal Vein Embolization in the Treatment of Colorectal Liver Metastases

Background  Blockage of vascular endothelial growth factor (VEGF) in murine models has been shown to impair liver regeneration after partial hepatectomy. The aim of this study was to evaluate the effects of chemotherapy with or without bevacizumab (monoclonal antibody anti-VEGF) on liver regeneration after portal vein embolization (PVE) in the treatment of colorectal liver metastases and its possible effect on postoperative outcome after major liver resection. Methods  Records of 65 consecutive patients treated with or without preoperative chemotherapy (with or without bevacizumab) and PVE for colorectal liver metastases from September 1995 to February 2007 were reviewed from a prospective database. Future liver remnant (FLR) volume, degree of FLR hypertrophy after PVE, morbidity, mortality, and survival were analyzed. Results  Preoperative PVE was performed after chemotherapy in 43 patients and without chemotherapy in 22 patients. Among the 43 patients treated with chemotherapy, 26 received concurrent bevacizumab. After a median of 4 weeks after PVE, there was no difference in FLR volume increase among patients treated with or without chemotherapy. Similarly, there was no statistically significant difference in degree of FLR hypertrophy among patients treated without (mean, 10.1%) or with chemotherapy, with or without bevacizumab (8.8% and 6.8%) (P = .11). Forty-eight (74%) of 65 patients underwent extended right or right hepatectomy after PVE. No differences in morbidity and mortality were observed among patients treated with or without preoperative chemotherapy (with or without bevacizumab). Conclusion  Preoperative chemotherapy with bevacizumab does not impair liver regeneration after PVE. Liver resection can be performed safely in patients treated with bevacizumab before PVE. Presented at The Society of Surgical Oncology, 61st Annual Cancer Symposium, Chicago, IL, March 13–16, 2008.     

Laparoscopic Liver Surgery for Patients with Hepatocellular Carcinoma

Background Laparoscopic hepatectomy is feasible for hepatocellular carcinoma (HCC) today. This is a retrospective study of the patients with HCC treated by liver resection with a totally laparoscopic approach. Methods This study recruited 116 patients (92 male, 24 female) that underwent laparoscopic liver resection (LR) for HCC. Patients were divided into two groups: group I: (n = 97, 78 male,19 female) those with a volume of resection less than two segments; group II: (n = 19, 14 male, 5 female) those with a volume of resection of more than two segments. The distribution of the tumor-node–metastasis (TNM) stage of patients in the two groups was not significantly different. Results Patients resumed full diet on the second or third day after the operation, and the average length of hospital stay was 6 days. The operation time was 152.4 ± 336.3 min and 175.8 ± 57.4 min, while blood loss was 101.6 ± 324.4 mL and 329.2 ± 338.0 ml, for groups I and II, respectively. Five patients (5.2%) in group I and three patients (15.8%) in group II required blood transfusion (p = 0.122). The mortality rate was zero among our patients and complication rates were 6.2% and 5.2% for groups I and II, respectively. The 1-year, 3-year, and 5-year survival rates were 85.4%, 66.4%, and 59.4% for group I, and 94.7%, 74.2%, and 61.7% for group II, respectively, with no significant difference between two groups (p = 0.1237). Conclusion Laparoscopic liver resection is a procedure of significant risk and is more technically demanding in comparison with traditional open method. There was no significant difference in survival rates, based on the volume of resection. Laparoscopic surgery should be performed in selected patients as the postoperative quality of life of patients is better than that with open resection.     

Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas

We examined the effect of preoperative chemoradiotherapy on the ability to obtain pathologically negative resection margins in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between 1987 and 2000, 100 patients underwent Whipple resection with curative intent for primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six margins (proximal and distal superior mesenteric artery, proximal and distal superior mesenteric vein, pancreas, retroperkoneum, common bile duct, and hepatic artery) was undertaken by either frozen section (pancreas and common duct) or permanent section. A margin was considered positive if tumor was present less than 1 mm from the inked specimen. Margins noted to be positive on frozen section were resected when-ever possible. Of the 100 patients treated, 47 (47%) underwent postoperative radiation and chemotherapy (group I) and 53 (53%) received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32 patients) or gemcitabine (21 patients). Patient demographics and operative parameters were similar in the two groups, with the exception of preoperative tumor size (CT scan), which was greater in group II (P <0.001), and number of previous operations, which was greater in group II (P <0.0001). Statistical analysis of the number of negative surgical margins clear of tumor was performed using Fisher’s exact test. All patients (100%) had six margins assessed for microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%) of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47 patients without preoperative therapy had more than one margin with disease extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group receiving preoperative therapy (P = 0.013). Survival analysis reveals a significant increase in survival in margin-negative patients (P = 0.02). Similarly, a strong trend toward improved disease-free and overall survival is seen in patients with a single positive margin vs. multiple margins. Overall, we find a negative impact on survival with an increasing number of positive margins (P = 0.025, hazard ratio 1.3). When stratified for individual margin status, survival was decreased in patients with positive superior mesenteric artery (P = 0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a significant increase in disease-free or overall survival for patients receiving preoperative therapy (P = 0.07). Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

Preoperative Chemotherapy and the Outcome of Liver Resection for Colorectal Metastases

Background Neoadjuvant systemic chemotherapy is being increasingly used prior to liver resection for colorectal metastases. Oxaliplatin has been implicated in causing structural changes to the liver parenchyma, and such changes may increase the morbidity and mortality of surgery. Patients and Methods A retrospective study was undertaken of 101 consecutive patients who had undergone liver resection for colorectal metastases in two HPB centers. Preoperative demographic and premorbid data were gathered along with liver function tests and tumor markers. A subjective assessment of the surgical procedure was noted, and in-hospital morbidity and mortality were calculated. The effect of preoperative chemotherapy on short-term and long-term outcome was analyzed, and actuarial 1 and 3 year survival was determined. Results Patients who received neoadjuvant chemotherapy had a higher number of metastases (median 2, range 1–8 versus median 1, range 1–5; P = 0.019) and more had synchronous tumors (24 patients versus 8; P < 0.001). Overall morbidity was 37% and hospital mortality was 3.9%. Operative and in-hospital outcome was not influenced by chemotherapy. Long-term survival was worse in patients who had received preoperative chemotherapy (actuarial 3-year survival 62% versus 80%; P = 0.04). Conclusions This study shows no evidence that neoadjuvant chemotherapy, and in particular oxaliplatin, increases the risk associated with liver resection for colorectal metastases. Long-term outcome is reduced in patients receiving preoperative chemotherapy, although they have more advanced disease.     

Major Liver Resections Synchronous with Colorectal Surgery

Background Surgical strategy in liver metastases synchronous to colorectal cancer remains controversial. The aim of this study was to evaluate feasibility and short-term outcomes of major hepatectomies synchronous to colorectal surgery. Methods Between January 1985 and December 2004, 79 patients underwent major hepatectomy for metastases synchronous to colorectal cancer; 31 underwent synchronous hepatectomy and colorectal surgery, and 48 underwent delayed liver resection. Results The synchronous group had a higher rate of right colectomy (38.7% vs. 18.8%, P = .0499) and larger metastases (8 vs. 5.3 cm, P = .0032). Mortality (one patient in synchronous group), morbidity, and anastomotic leak rates were similar in the two groups. Colon-related morbidity did not cause adjunctive liver complications. Hospitalization in delayed hepatectomies was shorter (10.4 days vs. 13.9 days, P = .0021). Blood and plasma transfusions were higher in synchronous resections (41.9% vs. 16.7%, P = .0131 and 54.8% vs. 31.3%, P = .0370); no differences were found in the last 10 years. Considering both surgical procedures (colorectal + liver resection), in delayed hepatectomies, morbidity was higher (56.3% vs. 32.6%, P = .0369) and hospitalization was longer (20.5 vs. 13.9 days, P = .00001). Nine patients underwent major hepatectomy at the same time as anterior rectal resection with no mortality (morbidity 22.2%, mean hospitalization 12.4 days). Conclusions Major hepatectomies can be safely performed at the same time as colorectal surgery in selected patients with synchronous metastases with similar short-term results, even in the presence of rectal cancer.     

Feasibility and Efficacy of Combination Therapy With Preoperative and Postoperative Chemoradiation, Extended Pancreatectomy, and Postoperative Liver Perfusion Chemotherapy for Locally Advanced Cancers of the Pancreatic Head

Background The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy.Methods Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days × 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed.Results After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04).Conclusions A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.     

Liver Resection of Colorectal Liver Metastases in Elderly Patients

Background  

The percentage of elderly patients with colorectal liver metastases (CLM) has increased. Liver resection remains the only curative therapy; data evaluating the outcome in this age group is limited. Aim of the present study was to determine if postoperative morbidity, mortality, and other independent predictors influence survival in patients ≥70 years undergoing liver resection for CLM.     

Radiofrequency Ablation for Metachronous Liver Metastasis from Colorectal Cancer after Curative Surgery

Background We compared outcomes of surgery and radiofrequency thermal ablation (RFA) in patients with metachronous liver metastases. Methods Between October 1995 and December 2005, 59 patients underwent hepatic resection and 30 underwent RFA for metachronous liver metastases. Patients with extra-hepatic metastases, those who underwent both types of treatment, and those with synchronous hepatic metastasis were excluded. Results The two groups had similar mean age, sex ratio, comorbid medical conditions, primary disease stage, and frequency of solitary metastases. Preoperative mean serum carcinoembryonic antigen (CEA) level was significantly higher in the RFA group (13.4 ng/mL vs. 7.7 ng/mL; p = 0.02). Mean diameter of hepatic metastases was significantly greater in the resection than in the RFA group (3.1 cm vs. 2.0 cm; p = 0.001). Recurrence after treatment of metastasis was observed in 18 of 30 (60.0%) RFA and 33 of 59 (56%) resection patients. Local recurrence at the RFA site was observed in 7 of 30 (23%) patients. Time to recurrence (15 vs. 8 months, p = 0.02) and overall survival (56 vs. 36 months, p = 0.005) were significantly longer in the resection than in the RFA group. In the 69 patients with solitary metastases of diameter ≤3 cm, time to recurrence (p = 0.004) and overall survival were significantly greater in the resection group. Conclusions Compared with hepatic resection, RFA for metachronous hepatic metastases from colorectal cancer was associated with higher local recurrence and shorter recurrence-free and overall survival rates, even in patients with solitary, small (≤3 cm) lesions.     

Survival Outcomes of Patients with Colorectal Liver Metastases Following Hepatic Resection or Ablation in the Era of Effective Chemotherapy

The outcome of patients with colorectal liver metastases (CLM) undergoing surgical resection in the era of effective chemotherapy is not widely reported. In addition, factors associated with disease-specific survival (DSS) in a contemporary series of patients are not well defined. Clinical, pathologic, and outcome data for 64 patients with CLM treated by a single surgeon in a multidisciplinary setting from February 2002 to October 2007 were examined. Hepatic resection was combined with radiofrequency ablation (RFA) in 23 (36%) cases. Secondary or tertiary resection was undertaken in 12 (19%) patients. Synchronous CLM were noted in 25 (39%) cases. Neoadjuvant chemotherapy was given to 41 (64%) patients. Following hepatic resection, adjuvant chemotherapy was administered in 52 (81%) cases. There was one (2%) operative mortality. One or more complications were noted in 24 (38%) patients. Median length of hospital stay was 7 (2–7) days. Five-year DSS and overall survival were 72% and 69%, respectively. Bilobar disease (p < 0.001), local tumor extension (p = 0.02), response to neoadjuvant chemotherapy (p = 0.005), preoperative portal vein embolization (p = 0.05), number of hepatic lesions (p = 0.03), positive resection margin (p < 0.001), and node-positive primary disease (p = 0.001) were prognostically significant factors on univariate analysis. On multivariate analysis, bilobar disease (p = 0.02) and local tumor extension (p = 0.02) were the only two independent prognostic factors. We conclude that, in patients with CLM, a multidisciplinary approach encompassing an aggressive surgical policy achieves excellent 5-year survival results with acceptable operative morbidity and mortality. Bilobar disease and local extrahepatic extension of cancer appear to be independent prognostic factors for long-term survival.