The Impact of Postoperative Complications on Long-Term Outcomes Following Curative Resection for Colorectal Cancer

Background This study aimed to investigate the impact of postoperative complications on long-term survival and disease recurrence in patients who underwent curative resection for colorectal cancer. Method Patients who underwent radical resection for colorectal cancer with curative intent from January 1996 to December 2004 were included. Operative mortality and morbidity were documented prospectively. Factors that might affect long-term outcome were analyzed with multivariate analysis. Results Curative resection was performed in 1657 patients (943 men), and the median age was 70 years (range: 24–94 years). The 30-day mortality was 2.4%, and the complication rate was 27.3%. Age over 70 years (P < .001, odds ratio: 2.06, 95% CI: 1.63–2.61), male gender (P = .001, odds ratio: 1.49, 95% CI: 1.19–1.88), emergency operation (P < .001, odds ratio: 3.14, 95% CI: 2.26–4.35) and rectal cancer (P < .001, odds ratio: 1.41, 95% CI: 1.25–1.61) were associated with a significantly higher complication rate. With exclusion of patients who died within 30 days, the median follow-up of the surviving patients was 45.3 months. The 5-year overall survival was 64.9%, and the overall recurrence rate was 29.1%. The presence of postoperative complications was an independent factor associated with a worse overall survival (P = .023, hazard ratio: 1.26; 95% CI: 1.03–1.52) and a higher overall recurrence rate (P = .04, hazard ratio: 1.26; 95% CI: 1.01–1.57). Conclusion The presence of postoperative complication not only affects the short-term results of resection of colorectal cancer, but the long-term oncologic outcomes are also adversely affected. Long-term outcomes can be improved with efforts to reduce postoperative complications.     

Perioperative Morbidity Affects Long-Term Survival in Patients Following Liver Resection for Colorectal Metastases

Background Hepatic resection is the treatment of choice in patients with colorectal liver metastases. Perioperative morbidity is associated with decreased long-term survival in several cancers. The aim of this study was to assess the impact of perioperative morbidity and other prognostic factors on the outcome of patients undergoing liver resection for colorectal metastases. Methods One hundred ninety seven patients undergoing liver resection with curative intent were investigated. The influence of prognostic factors, such as complications, tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow obstruction, and era and type of resection, was assessed using univariate and multivariate analysis. Complications were graded using an objective surgical complication classification. Results The 5-year survival rate was 38%, with a median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%. The perioperative morbidity and mortality rates were 30 and 2.5%, respectively. The median survival of patients with perioperative complications was 3.2 years, compared to 4.4 years in those patients without complications (p < 0.01). For patients with positive resection margins, the median survival was 2.1 years, compared 4.4 years in patients with a margin (p = 0.019). Conclusion Perioperative morbidity and a positive resection margin had a negative impact on long-term survival in patients following liver resection for colorectal metastases. This paper has been presented at the annual meeting of the Royal Australian College of Surgeons 2006 and was accepted for oral presentation at the IHPBA 2006 meeting in Edinburgh.     

Severe Postoperative Complications Adversely Affect Long-Term Survival After R1 Resection for Pancreatic Head Adenocarcinoma

Background

Survival after pancreatic head adenocarcinoma surgery is determined by tumor characteristics, resection margins, and adjuvant chemotherapy. Few studies have analyzed the long-term impact of postoperative morbidity. The aim of the present study was to assess the impact of postoperative complications on long-term survival after pancreaticoduodenectomy for cancer.

Methods

Of 294 consecutive pancreatectomies performed between January 2000 and July 2011, a total of 101 pancreatic head resections for pancreatic ductal adenocarcinoma were retrospectively analyzed. Postoperative complications were classified on a five-grade validated scale and were correlated with long-term survival. Grade IIIb to IVb complications were defined as severe.

Results

Postoperative mortality and morbidity were 5 and 57 %, respectively. Severe postoperative complications occurred in 16 patients (16 %). Median overall survival was 1.4 years. Significant prognostic factors of survival were the N-stage of the tumor (median survival 3.4 years for N0 vs. 1.3 years for N1, p = 0.018) and R status of the resection (median survival 1.6 years for R0 vs. 1.2 years for R1, p = 0.038). Median survival after severe postoperative complications was decreased from 1.9 to 1.2 years (p = 0.06). Median survival for N0 or N1 tumor or after R0 resection was not influenced by the occurrence and severity of complications, but patients with a R1 resection and severe complications showed a worsened median survival of 0.6 vs. 2.0 years without severe complications (p = 0.0005).

Conclusions

Postoperative severe morbidity per se had no impact on long-term survival except in patients with R1 tumor resection. These results suggest that severe complications after R1 resection predict poor outcome.     

T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases

Background  While tumor infiltrating lymphocytes (TIL) have been shown to independently predict survival in primary colorectal cancer, the prognostic implications of TIL in resectable colorectal cancer liver metastases (CRCLM) have not been previously defined. This study examines the correlation between TIL numbers and survival following hepatic resection. Methods  We studied patients who survived ≤2 or ≥10 years following CRCLM resection. Immunohistochemistry was performed on tissue microarrays (TMAs) to determine the number of T cells within CRCLM. Correlation between TIL frequency and ≤2 or ≥10 year survival was determined while controlling for established prognostic factors. Results  Of 162 patients, 104 survived ≤2 years and 58 survived ≥10 years. Independent correlates of 10-year survival following CRCLM resection included a high number of CD8 T cells, a low number of CD4 T cells, and a clinical risk score of ≤2 (P < 0.001). Among 10-year survivors, 31% of patients had a high number of CD8 T cells compared with 8% for ≤2 year survivors (P < 0.01). Surprisingly, only 22% of 10-year survivors had a high number of CD4 T cells, in contrast to 69% of those who died within 2 years (P < 0.001). The combination of CD8 and CD4 T cell counts was a more powerful predictor of survival than either marker alone. Conclusions  CRCLM T cell number is an independent correlate of long-term survival following liver resection. We conclude that CRCLM TIL analysis represents a potentially powerful prognostic tool which will require further validation prior to broad application.     

Five-Year Survival Following Hepatic Resection After Neoadjuvant Therapy for Nonresectable Colorectal [Liver] Metastases

Background: Surgical resection is the most effective treatment for colorectal liver metastases but only a minority of patients are candidates for a potentially curative resection. Our experience with neoadjuvant chemotherapy followed by resection and five years survival analysis of the patients treated is presented.Methods: Between February of 1988 and September of 1996, 701 patients with unresectable colorectal liver metastases were treated with neoadjuvant chemotherapy. Four categories of nonresectable disease were defined: large size, ill location, multinodularity, and extrahepatic disease. Liver resection was performed in those patients whose disease became resectable. After resection, the patients were followed up every 3 months. A 5-year survival analysis by the different categories described was performed.Results: Ninety-five patients (13.5%) were found to be resectable on reevaluation and underwent a potentially curative resection. There was no perioperative mortality, and the complication rate was 23%. As of December of 1999, 87 patients have completed 5 years of follow-up. The overall 5-year survival is 35% from the time of resection and 39% from the onset of chemotherapy. Respective 5-year survival rates are 60% for large tumors, 49% for ill-located lesions, 34% for multinodular disease, and 18% for liver metastases with extrahepatic disease. In this latter category, however, a 35% 5-year survival was found when all the patients with extrahepatic disease were analyzed rather than only those for whom extrahepatic disease was the main cause of nonresectability.Conclusions: Neoadjuvant chemotherapy enables liver resection in some patients with initially unresectable colorectal metastases. Long-term survival is similar to that reported for a priori surgical candidates.     

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.     

Recurrence and Survival Outcomes after Hepatic Resection with or without Cryotherapy for Liver Metastases from Colorectal Carcinoma

Background Some reports support resection combined with cryotherapy for patients with multiple bilobar colorectal liver metastases (CRLM) that would otherwise be ineligible for curative treatments. This series demonstrates long-term results of 415 patients with CRLM who underwent resection with or without cryotherapy. Methods Between April 1990 and January 2006, 291 patients were treated with resection only and 124 patients with combined resection and cryotherapy. Recurrence and survival outcomes were compared. Kaplan-Meier and Cox-regression analyses were used to identify significant prognostic indicators for survival. Results Median length of follow-up was 25 months (range 1–124 months). The 30-day perioperative mortality rate was 3.1%. Overall median survival was 32 months (range 1–124 months), with 1-, 3- and 5-year survival values of 85%, 45% and 29%, respectively. The overall recurrence rates were 66% and 78% for resection and resection/cryotherapy groups, respectively. For the resection group, the median survival was 34 months, with 1-, 3- and 5- year survival values of 88%, 47% and 32%, respectively. The median survival for the resection/cryotherapy group was 29 months, with 1-, 3- and 5-year survival values of 84%, 43% and 24%, respectively (P = 0.206). Five factors were independently associated with an improved survival: absence of extrahepatic disease at diagnosis, well- or moderately-differentiated colorectal cancer, largest lesion size being 4 cm or less, a postoperative CEA of 5 ng/ml or less and absence of liver recurrence. Conclusions Long-term survival results of resection combined with cryotherapy for multiple bilobar CRLM are comparable to that of resection alone in selected patients.     

Hepatic Pedicle Clamping Does Not Worsen Survival after Hepatic Resection for Colorectal Liver Metastasis: Results from a Systematic Review and Meta-analysis

Background

Hepatic pedicle clamping (HPC) has been demonstrated to be effective for short-term outcomes during hepatic resection. However, HPC-induced hepatic ischemia/reperfusion injury can accelerate the outgrowth of hepatic micrometastases in experimental studies. The conclusive evidence regarding effects of HPC on long-term patient outcomes after hepatic resection for colorectal liver metastasis (CRLM) has not been determined.

Methods

A comprehensive electronic literature search was performed to identify studies evaluating the oncological effects of HPC after hepatic resection for CRLM. The main outcome measures were intrahepatic recurrence (IHR), disease-free survival (DFS), and overall survival (OS). A meta-analysis was performed using the random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (CI).

Results

Four studies, with a total of 2,114 patients (73.7 % HPC, 26.3 % non-HPC), matched the inclusion criteria. Meta-analyses revealed that IHR (OR 0.88; 95 % CI 0.69–1.11; P = 0.27), DFS (OR 0.88; 95 % CI 0.70–1.10; P = 0.27) and OS (OR 0.99; 95 % CI 0.79–1.24; P = 0.90) did not differ significantly between the HPC and non-HPC groups.

Conclusions

This meta-analysis provides persuasive evidence that HPC during hepatic resection for CRLM has no significant adverse oncological outcomes. HPC should be considered an option during parenchymal liver resection from current available evidence.     

Hepatic Pedicle Clamping During Hepatic Resection for Colorectal Liver Metastases: No Impact on Survival or Hepatic Recurrence

Background

Hepatic pedicle clamping is often used during liver resection. While its use reduces blood loss and transfusion requirements, the long-term effect on survival and recurrence has been debated. This study evaluates the effect of hepatic pedicle clamping [i.e., Pringle maneuver (PM)] on survival and recurrence following hepatic resection for colorectal liver metastasis (CRLM).

Methods

Patients who underwent R0 resection for CRLM from 1991 to 2004 were identified from a prospectively maintained database. Operative, perioperative, and clinicopathological variables were analyzed. The primary outcomes were disease-free survival (DFS) and liver recurrence (LR). Disease extent was categorized using a well-defined clinical risk score (CRS). Subgroup analysis was performed for patients given preoperative systemic chemotherapy and postoperative pump chemotherapy.

Results

This study included 928 consecutive patients with median follow-up of 8.9 years. PM was utilized in 874 (94 %) patients, with median time of 35 min (range 1–181 min). On univariate analysis, only resection type (p < 0.001) and tumor number (p = 0.002) were associated with use of PM. Younger age (p = 0.006), longer operative time (p < 0.001), and multiple tumors (p = 0.006) were associated with prolonged PM (>60 min). There was no association between DFS, overall survival (OS) or LR and Pringle time. Neither the CRS nor use of neoadjuvant therapy stratified disease-related outcome with respect to use of PM.

Conclusions

PM was used in most patients undergoing resection for CRLM and did not adversely influence intrahepatic recurrence, DFS, or OS.     

Anterior Approach to Major Resection for Colorectal Liver Metastasis

Purpose

The aim of this study was to examine the merits of the anterior approach, if any, in colorectal liver metastasis (CRLM) resection.

Methods

Data of patients who underwent partial hepatectomy for CRLM were reviewed. Patients treated by the anterior approach were compared with patients treated by the conventional approach.

Results

Ninety-eight patients had right hepatectomy, extended right hepatectomy, or right trisectionectomy. Among them, 71 patients underwent the conventional approach (CA group) and 27 underwent the anterior approach (AA group). The two groups were comparable in demographic, pathological, and perioperative characteristics except that the AA group had higher levels of aspartate transaminase (median, 41 vs. 31 U/L; p?=?0.006) and alanine transaminase (median, 27 vs. 22 U/L; p?=?0.009), larger tumors (median, 7 vs. 4 cm; p?=?0.000), and more extensive resections (p <?0.001). The median overall survival was 40 months (range, 0.69–168.6 months) in the CA group and 33.7 months (range, 0.95–99.8 months) in the AA group (p?=?0.22), and the median disease-free survival was 9.7 months (range, 0.62–168.6 months) in the CA group and 6.2 months (range, 0.72–99.8 months) in the AA group (p?=?0.464). Univariate and multivariate analyses identified 4 independent prognostic factors for overall survival: lymph node status of primary tumor (HR 1.352, 95% CI 0.639–2.862, p =?0.034), intraoperative blood loss (HR 1.253, 95% CI 1.039–1.510, p =?0.018), multiple liver tumor nodules (HR 1.775, 95% CI 1.029–3.061, p =?0.039), and microvascular invasion (HR 2.058, 95% CI 1.053–4.024, p =?0.035).

Conclusions

The two approaches resulted in comparable survival outcomes even though the AA group had larger tumors and more extensive resections. The anterior approach allows better mobilization and easier removal of large tumors once the liver is opened up.

     

Long-Term Survival after Resection for Primary Hepatic Carcinoid Tumor

Background:Primary hepatic carcinoid tumors (PHCTs) are extremely rare, and fewer than 50 cases have been reported in the English-language literature. We report a patient with a PHCT and review the cases in the literature.Methods:Our patient presented with symptoms and underwent liver resection for PHCT and regional lymph node metastasis. He underwent two more liver resections over the following 7 years for recurrent PHCT. Cases reported in the English-language literature were reviewed and survival analysis was performed with the Kaplan-Meier method. The survival impacts of age, gender, tumor foci, extrahepatic metastasis, unilobar versus bilobar disease, and type of preoperative treatment were determined by means of log-rank test.Results:Our patient has been free of symptoms for 14 years of follow-up and free of disease for 8 years of follow-up. Forty-eight cases of PHCT were found in the literature, and 92% of these patients underwent resection. Actuarial 5- and 10-year survival for all patients was 78% and 59%, respectively, whereas for resected patients, 10-year survival was 68%. The administration of preoperative chemotherapy, radiation therapy, or chemoembolization did not impact survival, nor did age, gender, presence of extrahepatic metastasis, number of tumors, or distribution of the tumor within the liver.Conclusions:Resection is the treatment of choice for PHCT and has provided favorable outcomes. Resection for PHCT can be performed in most patients and offers long-term survival.     

Hepatic Resection for Colorectal Metastasis: Impact of Tumour Size

Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions.     

Postoperative Infectious Complications Impact Long-Term Survival in Patients Who Underwent Hepatectomies for Colorectal Liver Metastases: a Propensity Score Matching Analysis

Objective

Postoperative complications strongly impact the postoperative course and long-term outcome of patients who underwent liver resection for colorectal liver metastases (CRLM). Among them, infectious complications play a relevant role. The aim of this study was to evaluate if infectious complications still impact overall and disease-free survival after liver resection for CRLM once patients were matched with a propensity score matching analysis based on Fong’s criteria.

Methods

A total of 2281 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were matched with a 1:3 propensity score analysis in order to compare patients with (INF+) and without (INF?) postoperative infectious complications.

Results

Major resection (OR?=?1.69 (1.01–2.89), p?=?0.05) and operative time (OR?=?1.1 (1.1–1.3), p?=?0.05) were identified as risk factors of infectious complications. After propensity score matching, infectious complications are associated with overall survival (OS), with 1-, 3-, 5-year OS at 94, 81, and 66% in INF? and 92, 66, and 57% in INF+ respectively (p?=?0.01). Disease-free survival (DFS) was also different with regard to 1-, 3-, 5-year survival at 65, 41, and 22% in R0 vs. 50, 28, and 17% in INF+ (p?=?0.007).

Conclusion

Infectious complications are associated with decreased overall and disease-free survival rates.

     

Hepatic Hemodynamic Changes Following Stepwise Liver Resection

Aim

Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes.

Methods

To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups.

Results

Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %).

Conclusion

Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.