Long-term outcomes after surgical resection for gastric cancer liver metastasis: an analysis of 64 macroscopically complete resections

Purpose

The indication for hepatectomy in cases of gastric cancer liver metastases (GLM) remains unclear and it remains controversial whether surgical resection is beneficial for GLM. The objective of this retrospective study was to clarify the indications for and benefit of hepatectomy for GLM.

Methods

Seventy-three patients underwent hepatectomies for GLM from January 1993 to January 2011. Macroscopically complete (R0 or R1) resection was achieved in 64 patients. Among them, 32 patients underwent synchronous hepatectomy with gastrectomy and the remaining 32 patients underwent metachronous hepatectomy. Repeat hepatectomy was done in 14 patients for resectable intrahepatic recurrences. Clinicopathological factors were evaluated by univariate and multivariate analyses among patients who received macroscopically complete resection for those affecting survival.

Results

The overall 1-, 3-, and 5-year survival rates after macroscopically complete (R0 or R1) liver resection (n?=?64) for GLM were 84, 50, and 37?%, respectively, with a median survival of 34?months. Univariate analysis identified serosal invasion of the primary gastric cancer and blood transfusions during surgery as poor prognosis indicators. By multivariate analysis, serosal invasion of the primary gastric cancer and larger hepatic tumor (>5?cm in diameter) were found to be independent indicators of poor prognosis.

Conclusions

GLM patients with the maximum diameter of hepatic tumors of <5?cm and without serosal invasion of the primary gastric cancer are the best candidate for hepatectomy.     

Repeat Hepatectomy for Recurrent Liver Metastasis From Gastric Carcinoma

Background

The efficacy of repeat hepatectomy for recurrent hepatocellular carcinoma and colorectal liver metastases is widely accepted. However, the benefits of such treatment for intrahepatic recurrence of gastric cancer liver metastasis remain unknown. This study sought to clarify the survival benefit for patients undergoing repeat hepatectomy for gastric cancer liver metastasis.

Methods

A total of 73 patients underwent hepatectomy for gastric cancer liver metastasis from January 1993 to January 2011. Macroscopically curative surgery was performed in 64 patients. Among them, repeat hepatectomy was performed in 14 of the 37 patients with intrahepatic recurrence. Among these 14 patients, clinicopathologic factors were evaluated by univariate and multivariate analysis to identify the factors affecting survival.

Results

The overall 1-, 3-, and 5-year survival rates after a second hepatectomy were 71, 47, and 47 %, respectively. The median survival was 31 months. Operative morbidity and mortality rates of repeat hepatectomy were 29 and 0 %, respectively. Multivariate analysis identified the duration of the disease-free interval as the only independent significant factor predicting better survival.

Conclusions

In selected patients, repeat hepatectomy for recurrent gastric cancer liver metastasis may offer the same chance of cure as the primary hepatectomy. Disease-free intervals exceeding 12 months predict good patient survival after repeat hepatectomy.     

Response to Preoperative Chemotherapy Predicts Survival in Patients Undergoing Hepatectomy for Liver Metastases from Gastric and Esophageal Cancer

Background

The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM.

Methods

Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated.

Results

Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24 %, respectively. Postoperative morbidity and mortality rates were 32 and 4 %, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9 %, P?=?.005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0 %, P?P?=?.045).

Conclusion

For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.     

Secondary gastrectomy for stage IV gastroesophageal adenocarcinoma after induction-chemotherapy

Purpose

With improved chemotherapeutic regimens, metastasized gastric cancer may show a good response rendering an initially unresectable tumor resectable. We performed a retrospective analysis on the outcome of stage IV gastric cancer patients treated by chemotherapy followed by oncologic resection in a western institution.

Methods

From August 1988 to December 2010, a total number of 1,817 patients underwent surgery for gastric cancer at the Department of Surgery, Technical University of Munich. A retrospective analysis of our prospective gastric cancer database identified 58 patients with stage IV gastric cancer having undergone induction chemotherapy followed by surgery in an individualized treatment concept. After induction chemotherapy usually consisting of 2 cycles of PLF (cisplatin, 5-fluorouracil, leucovorin), resection was performed with or without removal of metastases in patients without disease progression. Patients were followed up until death or loss to follow up.

Results

The three most common metastatic locations were liver (27.6 %), distant lymph nodes (22.4 %), and peritoneum (19.0 %). Of patients, 13.8 % had metastases in more than one location. Thirty-day mortality was 5.2 %, 90-day mortality was 13.8 %, while overall postoperative morbidity accounted for 24 %. In 19 (32.8 %) patients, a complete resection without any macroscopic tumor residues was achieved. In 39 (67.2 %) patients, tumors could not be completely removed with either local residual disease or residual disease at distant sites. Overall median survival was 20 months, while patients without residual tumor survived significantly longer (72 months) than patients with residual disease (12 months, p?=?0.001).

Conclusion

Secondary surgery of metastasized gastric cancer may be justified in selected cases without progression under induction chemotherapy. An achievable complete removal of the primary tumor and metastases appears the main selection criterion for patients benefitting from this approach.     

Effect on Outcome of Recurrence Patterns After Hepatectomy for Colorectal Metastases

Background

Despite improvements in surgery and chemotherapy, most patients develop recurrence after hepatectomy for metastatic colorectal cancer. Data are lacking on the effect of these patterns on outcome.

Methods

A retrospective review of a prospectively maintained hepatobiliary database was performed. Pattern and timing of recurrence and outcome after recurrence were analyzed. Univariate and multivariate analyses of factors associated with outcome after recurrence were carried out.

Results

From January 1997 through May 2003, a total of 733 patients underwent hepatectomy for colorectal metastases. Of these, 637 patients (87%) were included in the analysis, and in 393 patients (62%), recurrence was documented at the time of last follow-up. Initial recurrence patterns included the following: liver only in 120 patients (31%), lung only in 107 (27%), other single sites in 49 (12%), and multiple sites in 117 (30%). Recurrence occurred within 2 years of hepatectomy in 75% of patients and after 3 years in 11%. Margins at hepatectomy, recurrence pattern, resected recurrence, and disease-free interval from time of colectomy to hepatic metastasis and from time of hepatectomy to recurrence were independently associated with survival as measured from the time of recurrence. Recurrence in the lung, resected recurrence, and time to recurrence after hepatectomy were associated with prolonged survival as measured from the time of hepatectomy and the time of recurrence.

Conclusions

The timing and pattern of recurrence after hepatic resection for metastatic colorectal cancer are important predictors of long-term survival.     

Pulmonary metastasectomy for gastric cancer: a 13-year single-institution experience

Purpose

Pulmonary metastases from gastric cancer are rare, and the role of surgery is unclear. The purpose of this study was to determine which patients with metachronous metastatic gastric cancer (MGC) might benefit from pulmonary resection.

Methods

Between 1998 and 2011, 12 patients underwent 14 pulmonary resections for MGC. We reviewed their clinical courses and evaluated their radiological findings.

Results

Solitary pulmonary lesions were identified for 11 metastases, and the remaining three showed multiple pulmonary lesions. Six patients received treatment for the metastases before pulmonary resection. Lobectomy was performed for five lesions and wedge resection was performed for the remaining nine lesions. At the median follow-up time of 23.0 months, four patients were alive without disease, and the median DFS following pulmonary resection was 6.6 months. The overall 5-year survival rate following pulmonary resection was 58.4 %. In a univariate analysis, the number of lesions and the tumor doubling time (TDT) were significant predictors of the DFS, although prior treatment was not a significant predictor of the DFS.

Conclusion

Pulmonary resection for MGC might be an effective therapeutic option when there is a solitary metastatic lesion that has a long TDT, even if the patient has been previously treated for metastases.     

Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

Background

In colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined.

Methods

A retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed.

Results

The number of positive regional nodes and LNR correlated with multiple sites of metastases (p?<?0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p?<?0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p?=?0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p?=?0.48).

Conclusions

In stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.     

Predictors for Early Recurrence After Hepatectomy for Initially Unresectable Colorectal Liver Metastasis

Background

Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.

Methods

We retrospectively studied 46 patients who underwent hepatectomy after chemotherapy for initially unresectable colorectal liver metastasis from 1997 to 2010.

Results

Recurrences occurred within 6 months after hepatectomy in 13 patients (37 %). The median survival time of 21.2 months and the 5-year survival rate of 0 % after hepatectomy in patients with recurrence within 6 months were significantly worse than those in patients with recurrence more than 6 months after hepatectomy. Recurrence in less than 6 months was significantly correlated with impossibility of anticancer therapy for recurrence after hepatectomy (p?=?0.01). Eight or more hepatic tumors after chemotherapy were the only predictor of recurrence within 6 months (p?=?0.01; odds ratio 9.6; 95 % confidence interval 1.5–60.6).

Conclusion

Recurrence within 6 months was significantly correlated with a poorer outcome following surgery for initially unresectable colorectal liver metastasis. Surgical indication for initially unresectable colorectal liver metastasis with eight or more hepatic tumors after chemotherapy should be considered carefully in the light of mental and physical status, co-morbidity, and alternative treatment plans.     

Chance of Cure Following Liver Resection for Initially Unresectable Colorectal Metastases: Analysis of Actual 5-Year Survival

Background

Survival with long-term follow-up following liver resection for unresectable colorectal liver metastases (CRLM) downsized by chemotherapy has rarely been reported. The aim of this study was to determine the chance of cure following liver resection for initially unresectable CRLM.

Methods

Between January 2000 and December 2009, 61 patients underwent hepatectomy for unresectable liver-only CRLM downsized after chemotherapy. Cure was defined as a recurrence-free interval of at least 5 years after primary hepatectomy.

Results

Resectability of CRLM was achieved after a mean number of 11 courses, and 42.6 % of patients underwent liver resection after ≥10 courses. Postoperative mortality was nil, and morbidity rate was 19.7 %. The 5- and 10-year actuarial overall survival rates were 42.6 and 16.0 %. Of 30 patients with a follow-up ≥5 years, 11 were alive, yielding a 5-year actual overall survival rate of 36.7 %, and 7 (23.3 %) were considered cured because they are alive without recurrence. On multivariate analysis, response to chemotherapy was the only independent predictor of both overall and disease-free survival.

Conclusions

Cure can be achieved in about 23 % of patients resected for initially unresectable CRLM downsized by chemotherapy. Liver resection can be safely performed in selected patients even after multiple courses of chemotherapy.     

Simultaneous resection for colorectal cancer and synchronous liver metastases

Purposes

The correct timing of hepatectomy in patients with synchronous colorectal liver metastases is unclear. The aim of this study was to assess the clinical value of simultaneous resection (SR) for patients with colorectal cancer and synchronous liver metastases.

Methods

Between January 2006 and December 2013, 158 patients underwent resection of primary colorectal cancer and liver metastases. Sixty-three patients possessed synchronous colorectal liver metastases. Of those with synchronous colorectal liver metastases, 41 patients (65 %) underwent SR, and 22 (35 %) underwent delayed resection (DR). The clinicopathologic and operative data and the surgical outcomes of the patients in the SR and DR groups were retrospectively analyzed.

Results

The type of primary/liver resection, liver resection time, total blood loss volume, R0 resection rate, and morbidity rate were similar between the two groups. The SR group was associated with a shorter total postoperative hospital stay (21 vs 32 days, p < 0.001). However, the overall survival rate was similar between the two groups (3-year survival, 65.6 % in the SR group versus 66.8 % in the DR group, p = 0.054).

Conclusion

Simultaneous resection of colorectal cancer and synchronous liver metastases is associated with a comparable morbidity rate and shorter hospital stay, even when following rectal resection and major hepatectomy.

     

A Systematic Review of Repeat Hepatectomy for Recurrent Colorectal Liver Metastases

Background

Selected patients with recurrent colorectal liver metastases (CLM) may be resectable by repeat hepatectomy approach. In this review, we aim to collate and evaluate the published evidence for repeat hepatectomy in patients with recurrent CLM.

Methods

Searches of the Medline and Embase databases were undertaken to identify studies of repeat hepatectomy in patients with recurrent CLM focusing on the perioperative treatment regimen, operative strategy, morbidity, technical success and survival outcomes.

Results

Twenty-two observational studies were reviewed. A total of 1,610 patients underwent second hepatectomy for recurrent CLM. The median percentage of extra-hepatic disease was 15 % (range, 0–39 %). Preoperative chemotherapy was reported in 5/22 studies. Major liver resection was undertaken in 25 % (range, 9–59 %) of patients and the R0 resection rate was 90 % (range, 77–96 %). Postoperative morbidity and mortality after the second hepatectomy were 23 % and 1.2 %, respectively. Recurrence rate after second hepatectomy was 63.9 % (range, 42–91 %) with a median follow-up period of 32 months (range, 19–59 months). Median overall survival was 35 months (range, 19–56 months). The 3-year and 5-year overall survival rates were 55 % (range, 11–82 %) and 42 % (range, 31–73 %), respectively.

Conclusion

Second hepatectomy is safe and feasible in selected patients with recurrent CLM and is associated with acceptable perioperative and survival outcomes. Future prospective studies are required to further define the patient selection criteria for repeat hepatectomy and the exact role of perioperative chemotherapy.     

Anastomotic Leak Following Low Anterior Resection in Stage IV Rectal Cancer is Associated with Poor Survival

Background

Anastomotic leak is a serious complication of low anterior resection (LAR). The risk of leak in stage IV rectal cancer patients treated with synchronous or staged resection of the primary tumour and metastatic sites has not been reported. We measured the incidence of anastomotic leak and its association with clinical outcome.

Methods

With institutional review board approval, patients undergoing LAR and resection of metastatic disease were analyzed from a prospectively collected colorectal database between 1992 and 2010. Data for use of ileostomy, clinical anastomotic leak, and clinical risk score (for liver metastases, n = 86) were collected. Categorical variables were compared with the χ² test. Estimated overall survival was compared using log-rank method and Cox regression analysis.

Results

A total of 184 patients with LAR and stage IV disease were identified. Of those, 123 had curative resection for disease at distant sites. 72 % underwent simultaneous resection, 28 % staged resection. Median follow-up was 2.9 years for survivors. Anastomotic leak occurred in 6.5 %. There was one perioperative death (not attributable to leak). Overall 3-year survival following a leak was significantly worse compared with patients without a leak (35 vs. 73 %, P = 0.01). Clinical leak was associated with worse survival when controlled for use of diverting stoma, operative year, clinical risk score, and timing of resection of metastatic disease.

Conclusions

In this series of patients with stage IV rectal cancer, anastomotic leak was uncommon. However, patients who developed a clinical leak following surgery had worse survival. This finding was independent of use of diverting stoma or staged resection.     

Liver transplantation for hilar cholangiocarcinoma—a single-centre experience

Background

Cholangiocarcinoma is an infrequent malignancy, often unresectable at the time of diagnosis. Liver transplantation may offer a chance for cure, but results in the past have been disappointing, prompting transplant centres to adopt multimodal treatment protocols and extreme patient selection.

Purpose

This study was designed to evaluate the outcome of patients with irresectable hilar cholangiocarcinoma undergoing liver transplantation in order to determine criteria for patient selection.

Methods

We reviewed our prospective cancer registry for patients with hilar cholangiocarcinoma treated by transplantation since 1997. Data were evaluated regarding tumour location, stage, overall survival, recurrence rates and prognostic factors.

Results

Liver transplantation with lymphadenectomy was realised in 16 patients with hilar cholangiocarcinoma. Seven patients received a living donor graft. Lymph node metastases were found in eight patients with a median of 13 harvested nodes and had a statistically significant negative impact on overall survival irrespective of tumour size. Only one patient underwent neoadjuvant brachytherapy and developed fatal septic complications; 3- and 5-year survival rates were 63 and 50 % in lymph node-negative patients without neoadjuvant treatment.

Conclusions

Acceptable survival rates can be achieved by transplantation for hilar cholangiocarcinoma with lymph node metastases as the only exclusion criterion. We recommend staging laparotomy with lymphadenectomy along the common hepatic artery prior to liver transplantation.     

“Cherry Picking”, a Multiple Non-anatomic Liver Resection Technique, as a Promising Option for Diffuse Liver Metastases in Patients with Neuroendocrine Tumours

Introduction

Liver metastases of GEP-NETs are a known major prognostic factor with a strong effect on patients’ survival. To date, various treatment options are available, whereas surgery remains the only curative option. Because large liver resections often cannot be performed due to insufficient remnant liver volume, a special operative technique, “cherry picking” (multiple nonanatomic liver resections), can be used as a tissue-preserving procedure.

Methods

Of 91 patients with various GEP-NETs, 16 patients were identified with synchronous or metachronous multifocal, bilobular liver metastases (>10). All were treated with “cherry picking.” Patient records were reviewed retrospectively and clinical data and pathology results were analyzed.

Results

Mean survival after primary tumour resection was 82.8 versus 41.2 months after liver surgery. All 16 patients are still alive. Mean recurrence-free survival after primary tumour operation was 49.8 versus 24.6 months after liver surgery. Complications of cherry picking included two postoperative biliary leakages and three small hepatic abscesses (conservative/interventional approach 25 % (n = 4), surgical approach 6.25 % (n = 1). There was no postoperative mortality. Initial hormonal symptoms (5/16 patients) completely disappeared postoperatively in 2 patients and were significantly decreased in 3 patients.

Conclusions

The tissue-preserving surgical technique “cherry picking” has developed due to improved imaging techniques and increased knowledge in liver anatomy, which has helped to make this approach safer and easier. Highly selected patients with multiple bilobular liver metastases of GEP-NET can benefit from this special surgical approach, also applicable for recurrent metastases.     

Unresectable Colorectal Liver Metastases: The Safety and Efficacy of Conversion Therapy Using Hepatic Arterial Infusion Immunochemotherapy with 5-Fluorouracil and Polyethylene Glycol-Interferon α-2a

Background

Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy.

Methods

Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors.

Results

With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09).

Conclusions

Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.     

Usefulness of Contrast-Enhanced Intraoperative Ultrasonography (CE-IOUS) in Patients with Colorectal Liver Metastases after Preoperative Chemotherapy

Aims

The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques.

Methods

From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography.

Results

Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n?=?9), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n?=?4), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p?=?0.047), resolution of at least one metastasis (p?=?0.011), and small liver metastases (largest lesion size ≤20 mm) after chemotherapy (p?=?0.007).

Conclusion

In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate.     

Circulating Tumor Cells and Prognosis of Patients with Resectable Colorectal Liver Metastases or Widespread Metastatic Colorectal Cancer: A Meta-Analysis

Background

We performed a systematic review and meta-analysis to investigate the prognostic value of tumor cells in blood (circulating tumor cells [CTCs]) or bone marrow (BM) (disseminated tumor cells) of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer (CRC).

Materials and Methods

The following databases were searched in May 2011: MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cochrane Library. Studies that investigated the association between tumor cells in blood or BM and long-term outcome in patients with metastatic CRC were included. We extracted hazard ratios (HRs) and confidence intervals (CIs) from the included studies and performed random-effects meta-analyses for survival outcomes.

Results

The literature search yielded 16 studies representing 1,491 patients. The results of 12 studies representing 1,329 patients were suitable for pooled analysis. The overall survival (HR, 2.47; 95 % CI 1.74–3.51) and progression-free survival (PFS) (HR, 2.07; 95 % CI 1.44–2.98) were worse in patients with CTCs. The subgroup of studies with more than 35 % CTC-positive patients was the only subgroup with a statistically significant worse PFS. All eight studies that performed multivariable analysis identified the detection of CTCs as an independent prognostic factor for survival.

Conclusion

The detection of CTCs in peripheral blood of patients with resectable colorectal liver metastases or widespread metastatic CRC is associated with disease progression and poor survival.     

Up-front Hepatic Resection for Metastatic Colorectal Cancer Results in Favorable Long-term Survival

Background

Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post–liver resection chemotherapy. We report the outcomes of patients based on this surgical approach.

Methods

A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002–2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method.

Results

A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8–80) months. The majority (n = 195, 60.9 %) had metachronous disease, and most patients (n = 286, 85 %) had a major hepatectomy (>3 segments). Thirty-six patients (11 %) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1 %, and perioperative morbidity occurred in 68 patients (20.2 %). Actual disease-free survival at 3 and 5 years was 46.2 % and 42 %, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7 % and 55 %, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95 % confidence interval): size of metastasis >6 cm (2.2; 1.3–3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0–3.8), N2 (2.4; 1.2–4.9)), synchronous disease (2.1; 1.3–3.5), and treatment with chemotherapy after liver resection (0.42; 0.23–0.75).

Conclusions

Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.     

Outcomes After Hepatic and Pulmonary Metastasectomies Compared With Pulmonary Metastasectomy Alone in Patients With Colorectal Cancer Metastasis to Liver and Lungs

Background

Surgical resection is the most effective treatment for colorectal cancer that has metastasized to the liver. Similarly, surgical resection improves survival for selected patients with pulmonary colorectal metastases. However, the indication for pulmonary metastasectomy is not clear in patients with both hepatic and pulmonary colorectal metastases. Therefore, we evaluated outcomes after pulmonary resection of colorectal metastases in patients with or without a history of curative hepatic metastasectomy.

Methods

We retrospectively analyzed 96 patients who underwent pulmonary metastasectomy from March 1999 to November 2009. Patients were grouped according to treatment: resection of pulmonary metastases alone (lung metastasectomy group) or resection of both hepatic and pulmonary metastases (liver and lung metastasectomy group). Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan–Meier analysis. Survival curves were compared using the log-rank test.

Results

The 5-year OS for all patients was 61.3 %, and the 5-year DFS was 26.7 %. Group comparisons showed that the 5-year OS of the lung metastasectomy group was significantly better than that of the liver and lung metastasectomy group (69 vs. 43 %; p = 0.030). However, the 5-year DFS rates of the lung metastasectomy group (25.8 %) and liver and lung metastasectomy group (28.0 %) did not differ significantly. Recurrence was higher after resection of both hepatic and pulmonary metastases than after pulmonary metastases alone (79 vs. 45 %; p = 0.025).

Conclusions

Resection of pulmonary colorectal metastases may increase survival. However, the combination of liver and lung metastasectomies had a worse prognosis than pulmonary metastasectomy alone. In selected patients, combined liver and lung metastasectomy can be beneficial and result in acceptable DFS.     

Impact of Simultaneous Diaphragm Resection During Hepatectomy for Treatment of Metastatic Colorectal Cancer

Introduction

For colorectal cancer patients with liver metastases involving the hepatic dome or invading the diaphragm, a concomitant diaphragm resection is often required to achieve negative surgical margins. The purpose of this study is to determine whether diaphragm resection during partial hepatectomy for metastatic colorectal cancer influences short-term perioperative outcomes and overall survival.

Methods

Demographics, treatments, and outcomes of 442 patients who underwent hepatic resection for metastatic colorectal cancer from 1996 to 2010 at a high-volume center were reviewed. Recurrence and survival were measured from the date of metastectomy. Actuarial curves were generated using the Kaplan?CMeier method and compared using log?Cranks testing. Multivariate predictors of worse survival were compared using a Cox-proportional hazards model.

Results

A total of 442 patients underwent hepatectomy for metastatic colorectal cancer. Of these, 34 required simultaneous diaphragm resection (DR) and 408 did not (LR). No significant differences existed in patient demographics or comorbidities. The DR group had longer median operative times (336 vs. 267?min, p?=?0.0008) but had comparable rates of perioperative morbidity and mortality. Median overall survival was shorter in the DR group compared to the LR group (18.8 vs. 36?months, p?=?0.0017). When controlling for potential cofounders, liver metastases size?>?5?cm (HR 1.45 95?% CI (1.08?C1.99), p?=?0.015) and diaphragm resection (HR?=?1.72 95?% CI (1.03?C2.86), p?=?0.038) predicted worse survival.

Conclusions

Simultaneous diaphragm resection during partial hepatectomy does not significantly influence perioperative morbidity or mortality despite longer operative times. However, patients who require diaphragm resection have less favorable survival rates as compared to those who do not.